tbRes List

TQ, Thymoquinone: Click to Expand ⟱

Features: Anti-oxidant, anti-tumor

Thymoquinone is a bioactive compound found in the seeds of Nigella sativa, commonly known as black seed or black cumin.
Pathways:
-Cell cycle arrest, apoptosis induction, ROS generation in cancer cells
-inhibit the activation of NF-κB, Suppress the PI3K/Akt signaling cascade
-Inhibit angiogenic factors such as VEGF, MMPs
-Inhibit HDACs, UHRF1, and DNMTs

-Note half-life 3-6hrs.
BioAv low oral bioavailability due to its lipophilic nature. Note refridgeration of Black seed oil improves the stability of TQ.
DIY: ~1 part lecithin : 2–3 parts black seed oil : 4–5 parts warm water. (chat ai)
Pathways:
- usually induce ROS production in Cancer cells, and lowers ROS in normal cells
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- May Low AntiOxidant defense in Cancer Cells: NRF2↓(usually contrary), GSH↓ HO1↓(contrary), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, VEGF↓, FAK↓, NF-κB↓, CXCR4↓, TGF-β↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PDKs↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, JAK">JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Scientific Papers found: Click to Expand⟱

1920-

JG,

TQ,

Plum,

Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line

in-vitro,

PC,

PANC1

ROS↑, thymoquinone, plumbagin and juglone were evaluated for their influence on reactive oxygen species (ROS) generation through 2,7-dichlorofluorescein diacetate (DCFDA) staining and they dramatically increased the intracellular ROS level in treated PANC-
TumCMig↓, inhibited PANC-1 cell migration
MMP9↓, reduced expression of matrix metalloproteinase-9 (MMP-9) in juglone-treated cells

2207-

SNP,

TQ,

Protective effects of Nigella sativa L. seeds aqueous extract-based silver nanoparticles on sepsis-induced damages in rats

in-vivo,

Nor,

Rats

*eff↑, Treatment with AgNPs led to a notable reduction in damages of liver, kidney, lung, stomach and duodenum.
*RenoP↑,
*hepatoP↑,
*MDA↓, AgNPs treated groups reduced the levels of tissues MDA and increased the levels of tissues SOD and GSH.
*SOD↑,
*GSH↑,
*TNF-α↓, The expression levels of TNF-α mRNA and IL-1β mRNA were reduced in the rats treated by silver nanoparticles.
*IL1β↓,

3407-

TQ,

Thymoquinone and its pharmacological perspective: A review

Review,

NA,

*antiOx↑, TQ has been reported for its antioxidant properties to combat oxidative stress in several literatures
*ROS↓, scavenges the highly reactive oxygen
*GSTs↑, induction of glutathione transferase and quinone reductase
*GSR↑,
*GSH↑, TQ induces the Glutathione production with simultaneous inhibition of superoxide radical production
*RenoP↑, Improved renal function against mercuric chloride, doxorubicin and cisplatin damage have been reported through TQ based induction of Glutathione
*IL1β↓, Decreased the levels of IL-1β, TNFα, MMP-13, cox-2 and PGE(2)
*TNF-α↓,
*MMP13↓,
*COX2↓, reducing COX-2 gene expression, it also inhibited colon cancer cell migration.
*PGE2↓,
*radioP↑, Normal cell protection from ionizing radiation in cancer cell treatment.
Twist↓, TQ treatment have evidenced the inhibition of TWIST1 promoter activity and reduces it expression in cancer cell line leading inhibition of epithelial-mesenchymal transition mediated metastasis
EMT↓,
NF-kB↓, inhibiting the NF-κB expression in breast cancer model of mice
p‑PI3K↓, TQ (20 M) decreased the activation of prostaglandin receptors EP2 and EP4 in LoVo colon cancer cells by reducing p-PI3K, p-Akt, p-GSK3, and -catenin.
p‑Akt↓,
p‑GSK‐3β↓,
DNMT1↓, TQ's anticancer effects are mediated by DNMT1-dependent (dependent DNA methylation mediates) DNA methylation,
HDAC↓, inhibiting histone deacetylase (HDAC)

3400-

TQ,

Chemo,

Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats

in-vitro,

Nor,

10 and 20 mg/kg b.w.)

TQ against CFZ-induced renal toxicity in rats

*GSH↑, 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes.
*SOD↑, TQ treatment (10 mg/kg) resulted in a significant rise in GSH (p < 0.001), CAT (p < 0.0001), and SOD
*lipid-P↓, highest doses of TQ (20 mg/kg) resulted in a significant reduction in lipid peroxidation compared to the CFZ group
*IL1β↑, TQ treatment considerably reduced IL-1β, IL-6, TNF-α, and caspase-3 concentrations.
*IL6↓,
*TNF-α↓,
*Casp3↓,
*Catalase↑,
*NRF2↑, TQ enhanced Nrf2 expression (p < 0.001), and this effect was only seen with 20 mg/kg
*RenoP↑, Degenerative kidney alterations caused by CFZ were reduced with TQ treatment (10 and 20 mg/kg

3401-

TQ,

Molecular mechanisms and signaling pathways of black cumin (Nigella sativa) and its active constituent, thymoquinone: a review

Review,

Var,

TumCP↓, thymoquinone can inhibit cancer cell proliferation through disruption of the PI3K/AKT pathway by upregulating phosphatase and tensin homolog
*antiOx↑, thymoquinone improve antioxidant enzyme activities, effectively scavenges free radicals, and thus protect cells from oxidative stress.
*ROS↓, modulate reactive oxygen species levels in tumor cells,
NRF2↑, regulate responses to oxidative stress and inflammation via Nrf2 and NF-κB pathways
NF-kB↓, Inhibits inflammatory response
TumCCA↑, arrest the cell cycle in the G2/M phase
*GABA↑, N. sativa and thymoquinone can elevate brain GABA content, and thus it may ameliorate epilepsy
P53↑,
P21↑,
AMPK↑,
neuroP↑, thymoquinone, exhibit various pharmacological activities, including neuroprotective, nephroprotective, cardioprotective, gastroprotective, hepatoprotective, and anti-cancer effects.
cardioP↑,
hepatoP↑,

3402-

TQ,

Enhanced Apoptosis in Pancreatic Cancer Cells through Thymoquinone-rich Nigella sativa L. Methanol Extract: Targeting NRF2/HO-1 and TNF-α Pathways

in-vitro,

PC,

PANC1

in-vitro,

PC,

MIA PaCa-2

tumCV↓, TQ significantly decreased viability at 20 μM
NRF2↑, TQ enhances the expression of NRF2 and its downstream target HO-1, promoting antioxidant responses and cellular protection.
HO-1↑,
TNF-α↓,

3403-

TQ,

A multiple endpoint approach reveals potential in vitro anticancer properties of thymoquinone in human renal carcinoma cells

in-vitro,

RCC,

786-O

TQ (1-100 μM) for 24 and 48 h

8.4 uM for 48 h

tumCV↓, TQ treatment clearly decreased cell viability in a concentration- and time-dependent manner.
ROS↑, TQ concentrations from 1 to 20 uM moderately increased ROS levels in approximately 20-30% comparing to control cells
TumCCA↑, an increase in the sub-G1 population was observed, especially at 30 μM,
eff↓, The co-treatment with GSH increases the cell viability of TQ-exposed cells
TumCI↓, As depicted in Fig. 8 (A-B), the % of invasion of 786-O cells treated with TQ (1 uM, 10 h) significantly decreased to 75.2% of controls

3404-

TQ,

The Neuroprotective Effects of Thymoquinone: A Review

Review,

Var,

Review,

AD,

Review,

Park,

Review,

Stroke,

*Inflam↓, anti-inflammatory, antioxidant, antimicrobial, antiparasitic, anticancer, hypoglycemic, antihypertensive, and antiasthmatic effects.
AntiCan↑,
*TNF-α↓, TQ treatment (2.5, 5, and 10 μM) inhibited the release of TNF-α, IL-6, and IL-1β.
*IL6↓,
*IL1β↓,
*NF-kB↓, TQ treatment (2.5, 5 and 10 μM) inhibited NF-κB-dependent neuroinflammation in BV2 microglia via decreasing iNOS protein levels, κB inhibitor phosphorylation, and binding of NF-κB to the DNA
*iNOS↓,
*NRF2↑, activation of the Nrf2/ARE signaling pathway by TQ resulted in the inhibition of NF-κB-mediated neuroinflammation.
*neuroP↑, TQ has neuroprotection potential against Aβ1-42 in rat hippocampal by ameliorating oxidative stress.
*MMP↑, Thymoquinone ameliorated Aβ1-42-induced neurotoxicity and prevented the mitochondrial membrane potential depolarization and finally reduced the oxidative stress.
*ROS↓,
*MDA↓, Thymoquinone decreased the neuronal cell death in the hippocampal CA1 region and MDA level and increased glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities after forebrain ischemia.
*GSH↑,
*Catalase↑,
*SOD↑,
*IL12↓, Thymoquinone exhibited anti-inflammatory effects by decreasing several cytokines, including TNF-α, NF-κB, IL-6, IL-1β, IL-12p40/70, (CCL12)/MCP-5, (CCL2)/MCP-1, GCSF, and Cxcl 10/IP-10 of, NO, PGE2, and iNOS.
*MCP1↓,
*IP-10/CXCL-10↓,
*PGE2↓,

3405-

TQ,

doxoR,

Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity and the underlying mechanism

vitro+vivo,

NA,

mice

*cardioP↑, thymoquinone can alleviate doxorubicin-induced cardiac toxicity in mice.
*NRF2↑, alleviate iron death in mouse cardiomyocytes by activating the Nrf2/HO-1 signaling pathway
*HO-1↑,
*ROS↓, Thymoquinone can also alleviate oxidative stress in mouse cardiomyocytes
*NQO1↑, similar effects on the expression levels of NQO1, COX-2, and NOX4
*COX2↓, implied
*NOX4↓, implied
*GPx4↑,
*FTH1↑, Reduces free iron, limiting ferroptosis
*p‑mTOR↓,
*TGF-β↓,

3406-

TQ,

Se,

A study to determine the effect of nano-selenium and thymoquinone on the Nrf2 gene expression in Alzheimer’s disease

in-vivo,

AD,

nano-selenium (5 mg/kg); thymoquinone (2 mg/kg);

50 albino male rats

*NRF2↑, Nrf2 mean expression levels in the nano-selenium-treated rats, the thymoquinone-treated rats, and the rats that were given both treatments all increased significantly compared to AD rats with no treatment.
*GSH↑, TQ and SeNPs demonstrated improvement in the levels of different biomarkers (Nrf2, Aβ-42, TNF-α, GSH & MDA) reversing them toward the normal levels.
*MDA↓, the mean brain tissue MDA levels in groups 3, 4, and 5 (27.37 ± 9.42, 29.23 ± 12.18, and 23.28 ± 4.89 nmol/mg protein, respectively) were significantly lower than those in group 2
*TNF-α↓, mean serum levels of TNF-α in groups 3, 4, and 5 (63.03 ± 11.07, 66.05 ± 9.96, and 36.41 ± 10.53 pg/ml) were found to be considerably lower than those in group 2

3398-

TQ,

5-FU,

Impact of thymoquinone on the Nrf2/HO-1 and MAPK/NF-κB axis in mitigating 5-fluorouracil-induced acute kidney injury in vivo

in-vivo,

Nor,

50-100mg/kg bw

Male albino Wistar rats

*RenoP↑, Pre-, post-, and cotreatment with TQ alleviated kidney injury
*TAC↑, by replenishing antioxidant reserves, reducing serum toxicity, decreasing ROS generation and lipid peroxidation, downregulating p38 MAPK/NF-κB axis/pathway proteins, and upregulating Nrf2 and HO-1,
*ROS↓, high-dose TQ alleviated ROS and H2O2 levels in groups III and IV
*lipid-P↓,
*p38↓,
*MAPK↓,
*NF-kB↓,
*NRF2↑,
*HO-1↑,
*MDA↓, TQ diminishes MDA levels
*GPx↑, GPx, GR, and CAT : restoration of GSH reserves and the abovementioned antioxidant enzymes
*GSR↑,
*Catalase↑,
*BUN↓, noticeable inhibition was observed in BUN, Cr, LDH, and KIM-1 at both doses
*LDH↓,
*IL1β↓, downregulation of IL-1β, diminishing inflammation

3408-

TQ,

Thymoquinone: A small molecule from nature with high therapeutic potential

Review,

AD,

Review,

Park,

*neuroP↑, The neuroprotective effect of TQ has been seen in various neurological disorders, including epilepsy, Parkinsonism, anxiety, depression, encephalomyelitis and Alzheimer’s disease
*hepatoP↑, Hepatoprotective activity
*cardioP↑, Cardioprotective activity
*Inflam↓, Anti-inflammatory activity
*antiOx↑, TQ is well known for its antioxidant activity
ChemoSen↑, combination of TQ with chemotherapeutic drugs shows very promising effects in different types of cancers and against different diseases in preclinical studies
eff↑, Along with curcumin and fluoxetine, TQ shows good activity as compared to alone
eff↑, Vascular endothelial growth factor (VEGF) activation lead to angiogenesis, which inhibited by a combination of resveratrol and TQ.
TumCP↓, TQ can inhibit tumor cell proliferation, inhibit carcinogen activation, arrest the cell cycle in different phases, induce apoptosis, inhibit proteasomes and inhibit angiogenesis.
TumCCA↑,
angioG↓,
cycA1↓, downregulation of cyclin A, cyclin D1, cyclin D2, cyclin E and cyclin-dependent kinases,
cycD1↓,
cycE↓,
CDK2↓,

3409-

TQ,

Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives

in-vivo,

Nor,

50 mg/kg

Forty adult male rats

*MDA↓, increased levels of malondialdehyde, TGF-β, CRP, NF-κB, TNF-α, IL-1β and caspase-3 associated with reduced levels of GSH, cyt-c oxidase, Nrf2 and IL-10. However, exposure of rats’ brain tissues to thymoquinone resulted ameliorated all these ef
*TGF-β↓,
*CRP↓,
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*Casp3↓,
*GSH↑,
*NRF2↑,
*IL10↑,
*neuroP↑, thymoquinone remediates sodium nitrite-induced brain impairment through several mechanisms including attenuation of oxidative stress
*ROS↓,
*Apoptosis↓,
*Inflam↓, TQ activates the Nrf2/ARE antioxidant mechanisms in its anti-inflammatory activity

3410-

TQ,

Anti-inflammatory effects of thymoquinone and its protective effects against several diseases

Review,

Arthritis,

*Inflam↓, anti-inflammatory, anti-oxidant, and anti-apoptotic properties in several disorders such as asthma, hypertension, diabetes, inflammation, bronchitis, headache, eczema, fever, dizziness and influenza
*antiOx↑, anti-inflammatory and anti-oxidant effects via several molecular pathways
*COX2↓, TQ has been shown to suppress COX2 expression and the ensuing generation of prostaglandins
*NRF2↑, TQ also attenuates inflammation via the Nrf2 pathway [28]. Heme-oxygenase 1 (HO-1) has been shown to be stimulated by TQ
*HO-1↑,
*IL1β↓, oral TQ treatment caused a decrease in several pro-inflammatory regulators, such as interleukin 1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNFα), interferon γ (IFNγ) and prostaglandin E2 PGE(2)
*IL6↓,
*TNF-α↓,
*IFN-γ↓,
*PGE2↓,
*cardioP↑, Cardioprotective activity of TQ through anti-inflammation
*Catalase↑, LPS diminished anti-oxidant enzymes including catalase (CAT) and superoxide dismutase (SOD) and the total thiol group. TQ treatment reduced these effects, restoring many of the LPS effects to basal levels
*SOD↑,
*Thiols↑,
*neuroP↑, Neuroprotective activity of TQ through anti-inflammation
*IL12↓, TQ diminished the levels of several cytokines such as IL-6, IL-1β, IL-12p40/70, chemokine C-C motif ligand 12 (CCL12)/monocyte chemotactic protein 5 (MCP-5), CCL2/MCP-1, granulocyte colony-stimulating factor (GCSF), and C-X-C motif chemokine 10 (Cxcl
*MCP1↓,
*CXCc↓,
*ROS↓, consistent with TQ’s efficacy in reducing ROS generation and the ensuing inflammation

3411-

TQ,

Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone

Review,

Var,

p‑STAT3↓, Thymoquinone inhibited the JAK2-mediated phosphorylation of STAT3 on the 727th serine residue in SK-MEL-28 cells
cycD1↓, levels of cyclin D1, D2, and D3 were reported to be reduced in STAT3-depleted SK-MEL-28 cells
JAK2↓, The JAK2/STAT3 pathway is inactivated by thymoquinone in B16-F10 melanoma cells
β-catenin/ZEB1↓, Levels of β-catenin and Wnt/β-catenin target genes, such as c-Myc, matrix metalloproteinase-7, and Met, were found to be reduced in thymoquinone-treated bladder cancer cells.
cMyc↓,
MMP7↓,
MET↓,
p‑Akt↓, Thymoquinone dose-dependently reduced the levels of p-AKT (threonine-308), p-AKT (serine-473), p-mTOR1, and p-mTOR2 in gastric cancer cells.
p‑mTOR↓,
CXCR4↓, Thymoquinone decreased the surface expression of CXCR4 on multiple myeloma cells
Bcl-2↓, Thymoquinone time-dependently decreased BCL-2 levels and simultaneously enhanced BAX levels
BAX↑,
ROS↑, Thymoquinone-mediated ROS accumulation triggered conformational changes in BAX that sequentially resulted in the activation of the mitochondrial apoptotic pathway
Cyt‑c↑, Thymoquinone effectively increased the release of cytochrome c into the cytosol
Twist↓, Thymoquinone downregulated TWIST1 and ZEB1 and simultaneously upregulated E-cadherin in SiHa and CaSki cell lines [82].
Zeb1↓,
E-cadherin↑,
p‑p38↑, Thymoquinone-induced ROS enhanced the phosphorylation of p38-MAPK in MCF-7 cells.
p‑MAPK↑,
ERK↑, The thymoquinone-induced activation of ERK1/2
eff↑, FR180204 (ERK inhibitor) significantly reduced the viability of thymoquinone and docetaxel-treated cancer cells [
ERK↓, Thymoquinone inhibited the proliferation, migration, and invasion of A549 cells by inactivating the ERK1/2 signaling cascade
TumCP↓,
TumCMig↓,
TumCI↓,

3412-

TQ,

Thymoquinone induces oxidative stress-mediated apoptosis through downregulation of Jak2/STAT3 signaling pathway in human melanoma cells

in-vitro,

Melanoma,

SK-MEL-28

in-vivo,

NA,

SK-MEL-28 tumor xenografts

Apoptosis↑, Q treatment induced apoptosis in SK-MEL-28 cells
JAK2↓, Interestingly, constitutive phosphorylation of Janus kinase 2 (Jak2) and signal transducer and activator of transcription 3 (STAT3) was markedly decreased following TQ treatment
STAT3↓,
cycD1↓, TQ treatment downregulated STAT3-dependent genes including cyclin D1, D2, and D3 and survivin
survivin↓,
ROS↑, TQ increased the levels of reactive oxygen species (ROS)
eff↓, , whereas pretreatment with N-acetyl cysteine (NAC), a ROS scavenger, prevented the suppressive effect of TQ on Jak2/STAT3 activation and protected SK-MEL-28 cells from TQ-induced apoptosis.

3413-

TQ,

Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src‑mediated phosphorylation of EGF receptor tyrosine kinase

in-vitro,

CRC,

HCT116

tumCV↓, TQ significantly reduced the viability of human colon cancer HCT116 cells in a concentration- and time-dependent manner
Apoptosis↓, TQ induced apoptosis, which was associated with the upregulation of Bax and inhibition of Bcl-2 and Bcl-xl expression
BAX↑,
Bcl-2↓,
Casp9↑, TQ also activated caspase-9,-7, and -3, and induced the cleavage of poly-(ADP-ribose) polymerase (PARP).
Casp7↑,
Casp3↑,
cl‑PARP↑,
STAT3↓, TQ attenuated the expression of STAT3 target gene products, such as survivin, c-Myc, and cyclin-D1, -D2, and enhanced the expression of cell cycle inhibitory proteins p27 and p21.
survivin↓,
cMyc↓,
cycD1↓,
p27↑,
P21↑,
EGFR↓, TQ attenuated the phosphorylation of upstream kinases, such as Janus-activated kinase-2 (JAK2), Src kinase and epidermal growth factor receptor (EGFR) tyrosine kinase
ROS↑, According to this study, TQ-induced cytotoxicity in DLD-1 colon cancer cells was associated with the generation of reactive oxygen species, activation of extracellular signal-regulated kinase and c-Jun-N-terminal kinase, and the cleavage of caspase-7

3414-

TQ,

Thymoquinone induces apoptosis through inhibition of JAK2/STAT3 signaling via production of ROS in human renal cancer Caki cells

in-vitro,

RCC,

Caki-1

tumCV↓, TQ significantly reduced the cell viability and induced apoptosis in Caki cells as evidenced by the induction of p53 and Bax, release of cytochrome c, cleavage of caspase-9, and -3 and PARP and the inhibition of Bcl-2 and Bcl-xl expression.
Apoptosis↑,
P53↑,
BAX↑,
Cyt‑c↑,
cl‑Casp9↑,
cl‑Casp3↑,
cl‑PARP↑,
Bcl-2↓,
Bcl-xL↓,
p‑STAT3↓, TQ inhibited the constitutive phosphorylation of signal transducer and activator of transcription-3 (STAT3) in Caki cells by blocking the phosphorylation of upstream Janus-activated kinase-2 (JAK2) kinases.
p‑JAK2↓,
STAT3↓, TQ attenuated the expression of STAT3 target gene products, such as survivin, cyclin D1, and D2.
survivin↓,
cycD1↓,
ROS↑, Treatment with TQ generated ROS in these renal cancer cells.
eff↓, Pretreatment of cells with ROS scavenger N-acetyl cysteine (NAC) abrogated the inhibitory effect of TQ on the JAK2/STAT3 signaling and rescued cells from TQ-induced apoptosis

3399-

TQ,

Anticancer Effects of Thymoquinone through the Antioxidant Activity, Upregulation of Nrf2, and Downregulation of PD-L1 in Triple-Negative Breast Cancer Cells

in-vitro,

BC,

MDA-MB-231

NA,

BC,

MDA-MB-468

ROS↓, The results show that TQ exhibits considerable antioxidant activity and decreases the generation of H2O2,
H2O2↓,
Catalase↑, at the same time increasing catalase (CAT) activity, superoxide dismutase (SOD) enzyme, and glutathione (GSH
SOD↑,
GSH↑,
NQO1↑, TQ treatment increased the levels of the different genes involved in the oxidative stress-antioxidant defense system PRNP, NQO1, and GCLM in both cell lines
GCLM↑,
NRF2↑, Nrf2 mRNA and protein expression were also significantly increased in TQ-treated TNBC cells
PD-L1↓, increased mRNA levels while decreasing PD-L1 protein expression in both cell lines
GSSG↑, Interestingly, a significant increase in GSSG was only found at 5 µM (p < 0.01), followed by a 50% significant reduction (p > 0.001) in GSSG at 15 µM of TQ.
GPx1⇅, TQ boosted GPX1 in MDA-MB-468 cells while decreasing GPX1 in MDA-MB-231 TNBC cells
GPx4↓, mda-mb-231

3415-

TQ,

The anti-neoplastic impact of thymoquinone from Nigella sativa on small cell lung cancer: In vitro and in vivo investigations

in-vitro,

Lung,

H446

1-100uM

tumCV↓, TQ reduced cell viability, induced apoptosis and cell cycle arrest, depleted ROS, and altered protein expression in associated signaling pathways.
TumCCA↑,
ROS↓, With regards to ROS in the current study, TQ dose-dependently decreased intracellular ROS levels in all SCLC cells except H446 cells upon 24-hour treatment with TQ.
CycB↑, TQ induced upregulation of cyclin B1 and cyclin D3 in H69-adherent and H446 cells, respectively. Cyclins A2, E1, and cdc2 were downregulated, while cyclin D3 was upregulated in H841-adherent cells
CycD3↑,
cycA1↓,
cycE↓,
cDC2↓,
antiOx↑, TQ acted as an antioxidant.
PARP↓, TQ downregulated intratumoral PARP
NRF2↓, TQ exerts its antioxidative effect by upregulating nuclear protein nuclear factor-erythroid 2 related factor 2 (Nrf2), hence amplifying antioxidant response element (ARE) expression.
ARE/EpRE↑,
eff↑, To confirm that the antioxidative action of TQ is anti-survival for cells, H841 cells were employed as a model and treated with NAC. NAC confirmed that ROS depletion led to a decrease in the cell viability of SCLC cells.

3397-

TQ,

Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer

Review,

CRC,

6-112uM (table 1)

ChemoSen↑, TQ can be used synergistically with chemotherapeutic agents to enhance their anticancer effects and to influence the expression of signaling pathways and other genes important in cancer development.
*Half-Life↝, These parameters remained associated with an elimination half-life (t1/2) of 63.43 ± 10.69 and 274.61 ± 8.48 min for intravenous and oral administration, respectively
*BioAv↝, TQ is characterized by slow absorption, rapid metabolism, rapid elimination and low physicochemical stability, which limits its pharmaceutical applications
*antiOx↑, Biologically active compounds from Nigella sativa have been shown to have antioxidant, antimicrobial, anti-inflammatory, antidiabetic, hepatoprotective, antiproliferative, proapoptotic, antiepileptic and immunomodulatory activities,
*Inflam↓,
*hepatoP↑,
TumCP↓, TQ exerts tumorigenic effects in a variety of ways, including modulation of the epigenetic machinery and effects on proliferation, the cell cycle, apoptosis, angiogenesis, carcinogenesis and metastasis
TumCCA↑,
Apoptosis↑,
angioG↑,
selectivity↑, TQ has low toxicity to normal cells, as confirmed by several studies, including studies on normal mouse kidney cells, normal human lung fibroblasts and normal human intestinal cells.
JNK↑, activation of c-Jun N-terminal kinases (JNK) and p38, as well as the phosphorylation of nuclear factor-?B (NF-?B) and the reduction of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) activi
p38↑,
p‑NF-kB↑,
ERK↓,
PI3K↓,
PTEN↑, showing higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3
Akt↓, TQ has also been shown to downregulate the PI3K/PTEN/Akt/mTOR and WNT/?-catenin pathways, which are critical for tumorigenesis
mTOR↓,
EMT↓, downregulating the epithelial to mesenchymal transition (EMT) transcription factors twist-related protein 1 (TWIST1) and E-cadherin
Twist↓,
E-cadherin↓,
ROS⇅, TQ has been shown to act as an antioxidant at low concentrations. Higher concentrations, however, induce apoptosis of cancer cells through the induction of oxidative stress
*Catalase↑, Thymoquinone upregulates the expression of genes encoding specific enzymes, such as catalase, superoxide dismutase, glutathione reductase, glutathione S-transferase and glutathione peroxidase, whose role is to protect against reactive oxygen species
*SOD↑,
*GSTA1↑,
*GPx↑,
*PGE2↓, TQ has the ability to downregulate NF-?B, interleukin-1?, tumor necrosis factor alpha, cyclooxygenase-2 (COX-2,) matrix metalloproteinase 13 (MMP-13), prostaglandin E2 (PGE2), the interferon regulatory factor, which are associated with inflammation a
*IL1β↓,
*COX2↓,
*MMP13↓,
MMPs↓, Figure 2
TumMeta↓,
VEGF↓,
STAT3↓, TQ affects the induction of apoptosis in cancer cells by blocking the signal transducer and activator of transcription 3 (STAT3) signaling
BAX↑, upregulation of Bax and inhibition of Bcl-2 and B-cell lymphoma-extra large (Bcl-xl) expression, as well as activated caspase-9, -7 and -3, and induced cleavage of poly (ADP-ribose) polymerase (PARP).
Bcl-2↑,
Casp9↑,
Casp7↑,
Casp3↑,
cl‑PARP↑,
survivin↓, TQ also attenuated the expression of STAT3 target gene products, such as survivin, c-Myc and cyclin-D1, -D2, and enhanced the expression of cell cycle inhibitory proteins p27 and p21
cMyc↓,
cycD1↓,
p27↑,
P21↑,
GSK‐3β↓, TQ reduces the levels of p-PI3K, p-Akt, p-glycogen synthase kinase 3 (p-GSK3?) and ?-catenin, thereby inhibiting downstream COX-2 expression, which in turn leads to a reduction in PGE2
β-catenin/ZEB1↓,
chemoP↑, results support the potential use of thymoquinone in colorectal cancer chemoprevention, as TQ is effective in protecting and treating the DMH-initiated early phase of colorectal cancer.

2353-

TQ,

The effects of thymoquinone on pancreatic cancer: Evidence from preclinical studies

Review,

PC,

BioAv↝, Along with its high lipophilicity, TQ has slow absorption, rapid metabolism, rapid elimination, low bioavailability, and low physicochemical stability.
BioAv↑, TQ encapsulation passively directs the drug to the liver and releases the drug in a controlled and effective manner, improving the oral bioavailability of this hydrophobic molecule.
MUC4↓, TQ can decrease the expression of mucin 4 glycoprotein (MUC4), expressed in an exacerbated way in pancreatic cancer cells,
PKM2↓, The pyruvate kinase M2 isoform (PKM2), involved in the metabolism of cancer cells, showed a negative regulation in the presence of a TQ + GEM CI of 36 ± 0.66 and 25 ± 5.25 on the MIA PaCa-2 and PANC-1 cells, respectively.
eff↑, TQ can exert a synergistic effect with juglone, another cytotoxic dietary molecule for pancreatic cancer cells
TumVol↓, TQ significantly reduced by 67 % of the tumour size of the animals
HDAC↓, TQ modifies the H4 acetylation by decreased histone deacetylases (HDACs) expression inducing the pro-apoptotic signalling pathway
NF-kB↓, 10 µM MiaPaCa-2, BxPC-3, AsPC-1, HPAC ↓cell growth, ↑apoptosis, ↑NF-κB, ↓Bcl-2, ↓Bcl-xL, ↓survivin, ↓XIAP, ↓COX-2, ↓PGE
Bcl-2↓,
Bcl-xL↓,
survivin↓,
XIAP↓,
COX2↓,
PGE1↓,

2139-

TQ,

Thymoquinone regulates microglial M1/M2 polarization after cerebral ischemia-reperfusion injury via the TLR4 signaling pathway

in-vivo,

Nor,

acute ischemic stroke using a mouse middle cerebral artery ischemia-reperfusion (I/R) model.

*TLR4↓, TQ inhibits the TLR4 / NF-κB pathway to regulate microglia polarization.
*NF-kB↓,
*Inflam↓, TQ attenuates inflammation in brain I/R by affecting microglia polarization.
*Hif1a↑, TQ can activate Hif-1α to counter-regulate the TLR4 / NF-κB pathway.
*motorD↑, TQ could improve the motor deficits caused by I/R.

2138-

TQ,

Thymoquinone has a synergistic effect with PHD inhibitors to ameliorate ischemic brain damage in mice

in-vivo,

Nor,

TQ (5 mg/kg

Male C57 mice were used to establish an ischemic stroke model by using endothelin-1

*Hif1a↑, TQ can activate the HIF-1α pathway and its downstream genes such as VEGF, TrkB, and PI3K, which in turn enhance angiogenesis and neurogenesis.
*VEGF↑,
*TrkB↑,
*PI3K↑,
*angioG↑, which in turn enhance angiogenesis and neurogenesis.
*neuroG↑,
*motorD↑, TQ has the same effect as DMOG to activate HIF-1 α and can improve motor dysfunction after ischemic stroke

2137-

TQ,

Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats

in-vivo,

Nor,

Male Wistar albino rats

*GSH↑, NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST)
*SOD↑,
*GSTA1↑,

2136-

TQ,

Nigella sativa and thymoquinone suppress cyclooxygenase-2 and oxidative stress in pancreatic tissue of streptozotocin-induced diabetic rats

in-vivo,

Nor,

streptozotocin (STZ)-induced diabetic rats

*COX2↓, TQ significantly suppressed the expression of COX-2 enzyme in the pancreatic tissue.
*lipid-P↓, TQ treatment also suppressed pancreatic tissue lipid peroxidation malondialdehyde levels and increased the level of superoxide dismutase antioxidant enzyme
*SOD↑, Treatment with TQ (GE) restored SOD levels to normal after 30 days, with significant increases in SOD levels compared with the STZ-induced diabetic group
*ROS↓, TQ suppressed the induced expression of the inflammatory enzyme COX-2 in pancreatic tissues of STZ diabetic rats, which in turn will lead to a decrease in the production of ROS and thus providing protection against the destruction of A cells.
*Inflam↓, results may be attributed to the anti-inflammatory properties of N. sativa and TQ.
*NF-kB↓, TQ dose- and time-dependently significantly reduced COX-2 expression in pancreatic ductal adenocarcinoma cells paralleled with inhibition of NF-kB

2135-

TQ,

Thymoquinone induces heme oxygenase-1 expression in HaCaT cells via Nrf2/ARE activation: Akt and AMPKα as upstream targets

in-vitro,

Nor,

HaCaT

TQ (1, 5,
10, 20 lM) for 6 h

skin cells

*HO-1↑, TQ induced the expression of HO-1 in HaCaT/ Cells treated with TQ (1, 5, 10, 20 lM) for 6 h induced the expression of HO-1 protein. maximal induction observed until 12 h and then returned to basal level time thereafter
*NRF2↑, Treatment with TQ increased the localization of nuclear factor (NF)-erythroid2-(E2)-related factor-2 (Nrf2) in the nucleus and elevated the antioxidant response element (ARE)-reporter gene activity.
*e-ERK↑, TQ induced the phosphorylation of extracellular signal-regulated kinase (ERK), Akt and cyclic AMP-activated protein kinase-α (AMPKα).
*e-Akt↑,
*AMPKα↑,
*ROS↑, Treatment of HaCaT cells with TQ resulted in a concentration-dependent increase in the intracellular accumulation of ROS (most occurs at 20uM concentration -see figure 5A)
*eff↓, pretreatment with N-acetyl cysteine (NAC) abrogated TQ-induced ROS accumulation, Akt and AMPKα activation, Nrf2 nuclear localization, the ARE-luciferase activity, and HO-1 expression in HaCaT cells
*tumCV∅, does not change much 1-20uM of TQ (normal cells) see figure 1A

2134-

TQ,

Modulation of Nrf2/HO1 Pathway by Thymoquinone to Exert Protection Against Diazinon-induced Myocardial Infarction in Rats

in-vivo,

Nor,

20 mg/kg p.o.

Male Sprague–Dawley rats

*ALAT↓, CK-MB, ALT, and AST) were shown. DN-treated rats showed significantly elevated enzyme activities as compared with control rats (147.33 ± 20.85, 110.67 ± 9.65, and 407.5 ± 31.3, respectively), and these abnormalities were alleviated in the TQ treatmen
*AST↓,
*MDA↓, TQ treatment to DN intoxicated rats significantly decreased MDA levels when compared with the DN alone group of rats, recommending the protective antioxidant role of TQ
*ROS↓,
*GSSG↓, GSSG that exhibit significant elevation in DN intoxication and normalized levels during TQ treatment.
*GSH↑, Administration of TQ with DN during the experimental period significantly increased GSH (heart and serum), vit-E and vit-C contents to near normal levels in the heart tissues and serum
*VitE↑,
*VitC↑,
*NRF2↑, TQ, significantly increased Nrf2, HO-1, NQO1, and SOD were noticed (22.2 ± 1.41, 37.2 ± 2.6, 33.37 ± 4.28, and 52.7 ± 3.05, respectively), when compared to the DN intoxicated group.
*HO-1↑,
*NQO1↑,
*SOD↑,
*cardioP↑, Restoration of body weight and improvement in heart weight in TQ treatment showed beneficial effects of TQ treatment.
*GSH/GSSG↑, TQ has a significant efficacy to control the levels of oxidized and reduced glutathione pools and able to decrease the GSSG/GSH ratio.
*GPx↑, TQ enhances GSH and GPx activities in DN-intoxicated rats by a beneficial mechanism.

2133-

TQ,

CUR,

Cisplatin,

Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling

in-vitro,

Nor,

HEK293

in-vivo,

NA,

Sprague–Dawley rats. 50 mg/kg BW Tq + 100 mg/kg BW Cur, with or without cisplatin-treatment were administered for 5 days

*creat↓, BUN, creatinine, CK and pro-inflammatory cytokines like TNF-α, IL-6 and MRP-1 to be elevated in the cisplatin-treated group while reducing glomerular filtration rate. Tq + Cur treatment significantly improved these conditions.
*TNF-α↓,
*IL6↓,
*MRP↓,
*GFR↑,
*mt-ATPase↑, antioxidant enzyme levels and mitochondrial ATPases were restored upon treatment,
*p‑Akt↑, Tq + Cur treatment increased the expressions of phosphorylated Akt, Nrf2 and HO-1 proteins while decreasing the levels of cleaved caspase 3 and NFκB in kidney homogenates.
*NRF2↑,
*HO-1↑,
*Casp3↓,
*NF-kB↓,
*RenoP↑, In summary, Tq + Cur had protective effects on cisplatin-induced nephrotoxicity and renal injury

2132-

TQ,

Thymoquinone treatment modulates the Nrf2/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis

in-vivo,

Nor,

10 and 20 mg/kg p.o.) for 28 days

Lung fibrosis was induced in rats

*Weight∅, BM administration resulted in a significant weight loss, which was ameliorated by TQ treatment.
*antiOx↑, BMILF was associated with a reduction in the antioxidant mechanisms and increased lipid peroxidation (abnormalities were diminished with TQ treatment)
*lipid-P↓,
*MMP7↓, elevated levels of inflammatory cytokines, MMP-7 expression, apoptotic markers (caspase 3, Bax, and Bcl-2), and fibrotic changes including TGF-β and hydroxyproline levels in lung tissues were evident. These abnormalities were diminished with TQ
*Casp3↓,
*BAX↓,
*TGF-β↓,
*Diff↑, differential cell count in BALF was significantly improved in rats treated with TQ
*NRF2↓, TQ also produced a dose-dependent reduction in the expressions of Nrf2, Ho-1 and TGF-β
*HO-1↓,
*NF-kB↓, NF-jB protein expression has been significantly and dose dependently decreased in TQ treated groups (10 and 20 mg/kg bw)
*IκB↑, IkBa has been significantly and dose dependently increase in TQ treated groups (10 and 20 mg/kg bw).

2131-

TQ,

Therapeutic impact of thymoquninone to alleviate ischemic brain injury via Nrf2/HO-1 pathway

in-vitro,

Stroke,

in-vivo,

Nor,

schemic brain damage in C57BL/6 J mice

*eff↑, TQ significantly mitigates brain damage and motor dysfunction after ischemic stroke.
*OS↑, observations coincided with curtailed cell death, inflammation, oxidative stress, apoptosis, and autophagy
*Inflam↓,
*ROS↓,
*NRF2↑, Most importantly, Nrf2/HO-1 signaling pathway activation by TQ was vital in the modulation of the above processes
*HO-1↑,

2130-

TQ,

Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model

in-vivo,

Nor,

rat

*eff↑, Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower.
*memory↑, TQ may also have a protective effect on learning and memory function.
*NRF2↑, TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus.
*HO-1↑,
*SOD↑,
*ROS↓, mechanism may be mediated by modulation of an antioxidative pathway.

2129-

TQ,

doxoR,

Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells

in-vitro,

BC,

MCF-7

25, 50 or 100 µM TQ

ChemoSen↑, TQ greatly inhibits doxorubicin-resistant human breast cancer MCF-7/DOX cell proliferation
PTEN↑, TQ treatment increased cellular levels of PTEN proteins
p‑Akt↓, resulting in a substantial decrease of phosphorylated Akt, a known regulator of cell survival.
TumCCA↑, TQ arrested MCF-7/DOX cells at G2/M phase and increased cellular levels of p53 and p21 proteins.
P53↑,
P21↑,
Apoptosis↑, TQ-induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of caspases and PARP cleavage in MCF-7/DOX cells.
MMP↓,
Casp↑,
cl‑PARP↑,
Bax:Bcl2↑, TQ treatment increased Bax/Bcl2 ratio via up-regulating Bax and down-regulating Bcl2 proteins.
eff↓, PTEN silencing by target specific siRNA enabled the suppression of TQ-induced apoptosis resulting in increased cell survival.
DNAdam↓, TQ treatment arrests MCF-7/DOX Cells in G2/M phase and induces DNA damage
p‑γH2AX↑, time-dependent increase in the phosphorylation of H2AX was observed following TQ treatment
ROS↑, DNA damage caused by TQ induced reactive species and oxidative stress.

3432-

TQ,

Thymoquinone: Review of Its Potential in the Treatment of Neurological Diseases

Review,

AD,

Review,

Park,

*memory↑, It could be utilized to treat drug misuse or dependence, and those with memory and cognitive impairment
*cognitive↑,
*ROS↓, TQ protects brain cells from oxidative stress, which is especially pronounced in memory-related regions.
*Inflam↓, TQ’s antioxidant and anti-inflammatory properties protect brain cells from damage and inflammation.
*antiOx↑,
*TLR1↓, TQ’s role in inhibiting Toll-like receptors (TLRs) and some inflammatory mediators, leading to reduced inflammation and neurotoxicity.
*AChE↓, TQ has been shown in clinical studies to block acetylcholinesterase (AChE) activity, which increases acetylcholine (ACh).
*MMP↑, TQ ameliorates and prevents Aβ-induced neurotoxicity and mitochondrial membrane depolarization by inhibiting ROS formation and reducing oxidative stress by antioxidant properties.
*neuroP↑, TQ has an essential role in the neuroprotective impact on hippocampal cells after cerebral ischemia through the inhibition of lipid peroxidation
*lipid-P↓,
*SOD↑, This effect is due to the antioxidant activity of TQ on the levels of the superoxide dismutase (SOD) and GSH activities.
*GSH↑,
*Ach↑, TQ has been shown in clinical studies to block acetylcholinesterase (AChE) activity, which increases acetylcholine (ACh).

3572-

TQ,

Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs

in-vivo,

Nor,

TQ, phospholipid nanoconstructs (PNCs)

*BioAv↑, After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-vis plain TQ suspension
*hepatoP↑, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vis pure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.
*ALAT↓,
*ALP↓,
*AST↓,

3571-

TQ,

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases

Review,

Var,

Review,

Stroke,

*BioAv↓, TQ has poor bioavailability and is hydrophobic, prohibiting clinical trials with TQ alone.
*BioAv↑, TQ nanoparticle formulation shows better bioavailability than free TQ,
*Inflam↓, anti-inflammatory effects of TQ involve multiple complex signaling pathways as well as molecular mechanisms
*antiOx↑, antioxidant activity from the inhibition of oxidative stress
*ROS↓,
*GSH↑, GSH prevented ROS-mediated oxidative stress damage
*GSTs↑, TQ was found to exhibit antioxidant properties by increasing the levels of GSH and glutathione-S-transferase enzyme alpha-3 (GSTA3)
*MPO↓, TQ significantly reduced the disease activity index (DAI) and myeloperoxidase (MPO) activity, protecting the internal microenvironment of the colon.
*NF-kB↓, TQ reduced NF-κB signaling gene expression while alleviating the increase of COX-2 in skin cells induced by 12-O-tetradecanoylphorbol-13-acetate
*COX2↓,
*IL1β↓, reduced the expression of inflammatory factors such as IL-1β, TNF-α, IFN-γ, and IL-6
*TNF-α↓,
*IFN-γ↓,
*IL6↓,
*cardioP↑, TQ may exhibit substantial effects in the control of inflammation in CVD
*lipid-P↓, TQ reduces lipid accumulation and enhances antioxidant capacity and renal function.
*TAC↑,
*RenoP↑,
Apoptosis↑, Breast cancer TQ induces apoptosis and cell cycle arrest; reduces cancer cell proliferation, colony formation, and migration;
TumCCA↑,
TumCP↓,
TumCMig↓,
angioG↓, Colorectal Cancer (CRC) TQ inhibits the angiogenesis
TNF-α↓, Lung cancer TQ inhibits tumor cell proliferation by causing lung cancer cell apoptosis to significantly arrest the S phase cell cycle and significantly reduce the activity of TNF-a and NF-κB
NF-kB↓,
ROS↑, Pancreatic cancer TQ significantly increases the level of ROS production in human pancreatic cancer cells
EMT↓, TQ initiates the miR-877-5p and PD-L1 signaling pathways, inhibiting the migration and EMT of bladder cancer cells.
*Aβ↓, TQ significantly reduced the expression of Aβ, phosphorylated-tau, and BACE-1 proteins.
*p‑tau↓,
*BACE↓,
*TLR2↓, Parkinson’s disease (PD) TQ inhibits activation of the NF-κB pathway. TQ reduces the expression of TLR-2, TLR-4, MyD88, TNF-α, IL-1β, IFN-β, IRF-3, and NF-κB.
*TLR4↓,
*MyD88↓,
*IRF3↓,
*eff↑, TQ pretreatment produced a dose-dependent reduction in the MI area and significantly reduced the elevation of serum cardiac markers caused by ISO.
eff↑, Curcumin and TQ induced apoptosis and cell cycle arrest and reduced cancer cell proliferation, colony formation, and migration in breast cancer cells
DNAdam↑, nanomedicine with TQ that induced DNA damage and apoptosis, inhibited cell proliferation, and prevented cell cycle progression
*iNOS↓, TQ significantly reduced the expression of COX-2 and inducible nitric oxide synthase (iNOS)

3570-

TQ,

Thymoquinone alleviates the experimentally induced Alzheimer's disease inflammation by modulation of TLRs signaling

in-vivo,

AD,

 rat model of AD induced by a combination of aluminum chloride (AlCl3

*Inflam↓, (TQ), the main active constituent of Nigella sativa oil, has been reported by several previous studies for its potent anti-inflammatory effect.
*Aβ↓, TQ improved AD rat cognitive decline, decreased Aβ formation and accumulation, significantly decreased TNF-α and IL-1β at all levels of doses
*TNF-α↓, TQ treatment at all levels of doses caused a significant decrease in the rats brain content of TNF-a compared to AD group reach- ing 39.85, 18.22, and 30.37 versus 65.30, r
*IL1β↓,
*TLR2↓, and significantly downregulated the expression of TLRs pathway components as well as their downstream effectors NF-κB and IRF-3 mRNAs at all levels of doses ( p < 0.05).
*IRF3↓,
*TLR4↓, TQ inhibits TLR-2 and TLR-4 and their downstream signaling molecule in a dose independent manner
*memory↑, TQ improves learning and memory ability in AD rat model
*NF-kB↓, TQ at all levels of doses for 14 consecutive days caused a significant decrease in NF-B expression
*MyD88↓, TQ middle dose (20 mg/kg) significantly downregulated the expression of TLR-2 by 82.74% and 77.94% and the expression of TLR-4 by 84.35% and 63.30%, the expression of MyD88 by 79.65% and 68.36%, the expression of TRIF by 25.90% and 76.75%,
*TRIF↓,
*BBB↑, t crosses the blood brain barrier and exerts diverse therapeutic effects with respect to neuroinflammation.
*cognitive↑, Thus, we can hypothesize that TQ could improve cognition and the brain morphological changes by attenuating the detrimental inflammatory effect of the pro-inflammatory cytokines release

3565-

TQ,

Thymoquinone as a potential therapeutic for Alzheimer’s disease in transgenic Drosophila melanogaster model

*cognitive↑, TQ at both concentrations resulted in a significant increase in behavioral activity, a significant reduction in the amount of reactive oxygen species (ROS), and restoration of depleted superoxide dismutase (SOD) and acetylcholine esterase (AChE) acti
*ROS↓,
*SOD↑,
*AChE↝, TQ was significantly evident in AChE activity since the enzyme activity was restored to 75.38% on day 15 and 92.23% on day 30
*Aβ↓,

3564-

TQ,

The Potential Neuroprotective Effect of Thymoquinone on Scopolamine-Induced In Vivo Alzheimer's Disease-like Condition: Mechanistic Insights

in-vivo,

AD,

Thirty mice

*Inflam↓, Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics.
*AntiCan↑,
*antiOx↑,
*neuroP↑, TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity.
*cognitive↑, TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes,
*Aβ↓, significant decrease in the deposition of amyloid beta (Aβ).
*PPARγ↑, TQ showed a significant upregulation for PPAR-γ, synapsin-2, and miR-9
*NF-kB↓, pretreatment of the mice with TQ significantly (p < 0.001) lowered NF-κB by 62.68%
*p‑tau↓, TQ significantly (p < 0.001) decreased Ptau by 58.33% relatively to the disease control group
*MMP↑, Pretreatment with TQ restored the mitochondrial membrane potential (MMP)
*memory↑, Poorgholam et al. (2018), who elucidated that TQ ameliorated learning functioning and memory loss in a rat model of AD
*NF-kB↓, inhibitory effect of TQ on the activation of NF-κB
*ROS↓, TQ may possess neuroprotective properties hampering the mitochondrial membrane depolarization, ROS generation, and Aβ deposition in neurotoxicity model

3563-

TQ,

Thymoquinone (TQ) demonstrates its neuroprotective effect via an anti-inflammatory action on the Aβ(1–42)-infused rat model of Alzheimer's disease

in-vivo,

AD,

A rat model of AD was established in 6 month-old rats

*memory↑, TQ treatment ameliorated both impaired memory performance and IFN-γ levels
*IFN-γ↑,
*neuroP↑, TQ might be a strong candidate for preventing or delaying the symptoms of AD by reducing neurotoxicity via its anti-inflammatory activity
*Inflam↓,
*cognitive↑, recovery role of TQ in cognitive functions was also demonstrated in distinct models of neurodegeneration

3561-

TQ,

Studi In Silico Potensi Piperine, Piperlongumine, dan Thymoquinone Sebagai Obat Alzheimer

NA,

AD,

*AChE↓, For interaction with AChe, piperine PIP is the best, followed by piperlongumine PL and TQ.
*BBB↑, TQ was able to penetrate the blood brain barrier (BBB) easily and has potentially active biological activity

3560-

TQ,

Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes

in-vivo,

AD,

orally TQ (20 mg/kg/dose) dissolved in corn oil
daily for 14 consecutive days

Forty Sprague Dawley male albino rats

*cognitive↑, TQ significantly improved cognition
*SOD↑, TQ significantly increased SOD and TAC and decreased AChE activities.
*TAC↑,
*AChE↓,
*MDA↓, It also decreased MDA and NO levels as well as TNF-α immunoreactivity and increased BDNF and Bcl-2 levels as well as ACh immunoreactivity.
*NO↓,
*TNF-α↓,
*Bcl-2↑,
*Ach↑,
*neuroP↑, These results indicate that TQ holds potential for neuroprotection and may be a promising approach for the treatment of neurodegenerative disorders.

3559-

TQ,

Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer’s disease

Review,

AD,

Review,

Var,

*antiOx↑, promising potential in the prevention and treatment of AD due to its significant antioxidative, anti-inflammatory,
*Inflam↑, anti-inflammatory activity of TQ is mediated through the Toll-like receptors (TLRs)
*AChE↓, In addition, it shows anticholinesterase activity and prevents α-synuclein induced synaptic damage.
AntiCan↑, NS plant, has been proven to have a wide range of pharmacological interventions, including antidiabetic, anticancer, cardioprotective, retinoprotective, renoprotective, neuroprotective, hepatoprotective and antihypertensive effects
*cardioP↑,
*RenoP↑,
*neuroP↑,
*hepatoP↑,
TumCG↓, potential ability to inhibit tumor growth by stimulating apoptosis as well as by suppression of the P13K/Akt pathways, cell cycle arrest and by inhibition of angiogenesis
Apoptosis↑,
PI3K↓,
Akt↑,
TumCCA↑,
angioG↓,
*NF-kB↓, TQ inhibits nuclear translocation of NF-kB which subsequently blocks the production of NF-kB mediated neuroinflammatory cytokines
*TLR2↓, TQ administration at different doses (10, 20, 40 mg/kg) significantly down-regulated the mRNA expression of TLR-2, TLR-4, MyD88, TRIF and their downstream effectors Interferon regulatory factor 3 (IRF-3)
*TLR4↓,
*MyD88↓,
*TRIF↓,
*IRF3↓,
*IL1β↓, TQ also inhibits LPS induced pro-inflammatory cytokine release like IL-1B, IL-6 and IL-12 p40/70 via its interaction with NF-kB
*IL6↓,
*IL12↓,
*NRF2↑, Nuclear erythroid-2 related factor/antioxidant response element (Nrf 2/ARE) being an upstream signaling pathway of NF-kB signaling pathway, its activation by TQ
*COX2↓, TQ also inhibits the expression of all genes regulated by NF-kB, i.e., COX-2, VEGF, MMP-9, c-Myc, and cyclin D1 which distinctively lowers NF-kB activation making it a potentially effective inhibitor of inflammation, proliferation and invasion
*VEGF↓,
*MMP9↓,
*cMyc↓,
*cycD1↓,
*TumCP↓,
*TumCI↓,
*MDA↓, it prevents the rise of malondialdehyde (MDA), transforming growth factor beta (TGF-β), c-reactive protein, IL1-β, caspase-3 and concomitantly upregulates glutathione (GSH), cytochrome c oxidase, and IL-10 levels [92].
*TGF-β↓,
*CRP↓,
*Casp3↓,
*GSH↑,
*IL10↑,
*iNOS↑, decline of inducible nitric oxide synthase (iNOS) protein expression
*lipid-P↓, TQ prominently mitigated hippocampal lipid peroxidation and improved SOD activity
*SOD↑,
*H2O2↓, TQ is a strong hydrogen peroxide, hydroxyl scavenger and lipid peroxidation inhibitor
*ROS↓, TQ (0.1 and 1 μM) ensured the inhibition of free radical generation, lowering of the release of lactate dehydrogenase (LDH)
*LDH↓,
*Catalase↑, upsurge the levels of GSH, SOD, catalase (CAT) and glutathione peroxidase (GPX)
*GPx↑,
*AChE↓, TQ exhibited the highest AChEI activity of 53.7 g/mL in which NS extract overall exhibited 84.7 g/mL, which suggests a significant AChE inhibition.
*cognitive↑, Most prominently, TQ has been found to regulate neurite maintenance for cognitive benefits by phosphorylating and thereby activating the MAPK protein, particularly the JNK proteins for embryogenesis and also lower the expression levels of BAX
*MAPK↑,
*JNK↑,
*BAX↓,
*memory↑, TQ portrays its potential of spatial memory enhancement by reversing the conditions as observed by MWM task
*Aβ↓, TQ thus, has been shown to ameliorate the Aβ accumulation
*MMP↑, improving the cellular activity, inhibiting mitochondrial membrane depolarization and suppressing ROS

3558-

TQ,

Behavioral and histological study on the neuroprotective effect of thymoquinone on the cerebellum in AlCl3-induced neurotoxicity in rats through modulation of oxidative stress, apoptosis, and autophagy

in-vivo,

AD,

Rats

*MDA↓, TQ showed a significant decrease (P < 0.05) in levels of malondialdehyde (MDA) and nitric oxide (NO), associated with a significant increase (P < 0.05) in reduced glutathione (GSH) level.
*NO↓,
*GSH↑,
*neuroP↑, AD & TQ group exhibited substantial preservation of the cerebellum's histological structure, the Purkinje cells number and transverse diameter showed a high significant increase (P < 0.001) and a significant increase (P < 0.05), respectively in compa
*cognitive↑, TQ showed improvement in behavioral tests, biochemical and histological findings.

3557-

TQ,

Thymoquinone protects against lipopolysaccharides-induced neurodegeneration and Alzheimer-like model in mice.

in-vivo,

AD,

 thirty-five Swiss mice

*Inflam↓, Thymoquinone is a known anti-inflammatory agent with a strong antioxidant activity.
*antiOx↑,
*cognitive↑, LPS significantly impaired performance in the Y-maze and NORT and induced behavioural abnormalities, compared to control. These were all ameliorated by treatment with TQ (15-30mg/kg).
*TNF-α↓, TQ also significantly (P<0.05) reduced the concentration of LPS-induced TNF-α, IL-1β, AChE and expressions of amyloid-beta, microglia and β-secretase/mRNA in hippocampus and prefrontal cortex.
*IL1β↓,
*AChE↓,
*IL10↑, TQ increased IL-10/mRNA, ChaT, synaptophysin in hippocampus and PFC
*ChAT↑,
*Aβ↓, depleted synaptic protein and Aβ accumulation.

3556-

TQ,

Thymoquinone alleviates the experimentally induced Alzheimer’s disease inflammation by modulation of TLRs signaling

in-vivo,

AD,

10, 20, and 40 mg/kg/day for 14 days

Ninety six Sprague-Dawley male albino rats

*Inflam↓, reported by several previous studies for its potent anti-inflammatory effec
*memory↑, TQ in improving learning and memory, using a rat model of AD induced by a combination of aluminum chloride (AlCl3) and d-galactose (d-Gal).
*cognitive↑, TQ improved AD rat cognitive decline, decreased Aβ formation and accumulation, significantly decreased TNF-α and IL-1β at all levels of doses
*Aβ↑,
*TNF-α↓, Fourteen consecutive days of TQ treatment at all levels of doses caused a significant decrease in the rats brain content of TNF-α compared to AD group reaching 39.85, 18.22, and 30.37 versus 65.30, respectively
*IL1β↓, TQ at all levels of doses significantly reduced the brain content of IL-1β compared to AD group reaching 36.55, 14.32, and 27.27 versus 53.65
*TLR2↓, TQ middle dose (20 mg/kg) significantly downregulated the expression of TLR-2 by 82.74% and 77.94% and the expression of TLR-4 by 84.35% and 63.30%,
*NF-kB↓, and significantly downregulated the expression of TLRs pathway components as well as their downstream effectors NF-κB and IRF-3 mRNAs at all levels of doses
*IRF3↓, expression of IRF-3 by 18.19% and 77.96%,
TLR4↓,
MyD88↓, expression of MyD88 by 79.65% and 68.36%
TRIF↓, expression of TRIF by 25.90% and 76.75%

3555-

TQ,

Thymoquinone administration ameliorates Alzheimer's disease-like phenotype by promoting cell survival in the hippocampus of amyloid beta1-42 infused rat model

in-vivo,

AD,

adult female rats.

*memory↑, TQ enhanced the memory performance of Aβ1-42 infused rats
*BAX↓, expression profiles of mir29c and Bax which significantly upregulated in the Aβ1-42-infused animals were attenuated by TQ
*Aβ↓, administration of TQ decreased the expressions of Aβ, phosphorylated-tau, and BACE-1 proteins. removing Aβ plaques and by restoring neuron viability
*p‑tau↓,
*AChE↓, a decrease of AChE level was noted in the Aβ+TQ group compared to that of the Aβ group
*p‑Akt↓, Q treatment decreased the phosphorylation of AKT
*Ach↑, When the degradation of acetylcholine by AChE enzyme decreases, increment in acetylcholine concentration leads to an improvement in memory
*Inflam↓, The healing effect of TQ on the reduction of the Aβ accumulation may be due to its anti-inflammatory effect

3554-

TQ,

Neuroprotective efficacy of thymoquinone against amyloid beta-induced neurotoxicity in human induced pluripotent stem cell-derived cholinergic neurons

in-vitro,

AD,

*GSH↑, TQ restored the decrease in the intracellular antioxidant enzyme glutathione levels and inhibited the generation of reactive oxygen species induced by Aβ1–42.
*ROS↓,
*neuroP↑, Thus, the findings of our study suggest that TQ holds a neuroprotective potential and could be a promising therapeutic agent to reduce the risk of developing AD and other disorders of the central nervous system.
*Casp3↓, Aβ1–42 (5 μM) induced about 90% increase in the caspase 3/7 activities (**P < 0.01). However, TQ (100 nM) co-treatment restored caspase 3/7 activities to control sample level
*Casp7↓,
*antiOx↓, strong antioxidant capabilities, TQ has been demonstrated to protect the brain and the spinal cord from oxidative damage generated by different pathologies induced by a variety of free radicals
*H2O2↓, Intriguingly, the co-treatment with TQ restored the content of GSH and significantly inhibited the apparent increase in H2O2.

3553-

TQ,

Study Effectiveness and Stability Formulation Nanoemulsion of Black Cumin Seed (Nigella sativa L.) Essential Oil: A Review

Review,

Nor,

*AntiCan↑, antimicrobial, antifungal, antiviral, anticancer, anti-inflammatory, immunomodulatory, anthelmintic, antidiabetic, antidepressant, antifertility, antioxidant, anti-agiing, analgesic, hepatoprotector, cardioprotector, neuroprotector and others.
*Inflam↓,
*antiOx↑,
*AntiAge↑,
*hepatoP↑,
*cardioP↑,
*neuroP↑,
*eff↑, Nano-delivery system in the formulation of the black cumin seed (Nigella sativa L.) essential oil nanoemulsion as a whole shows that there is an increase in the stability of the preparation and the effectiveness of the active substance

2128-

TQ,

Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo

in-vivo,

NA,

 female HR-1 hairless mouse skin

*COX2↓, Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2)
*NF-kB↓, TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin
*p‑Akt↓, Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase,
*p‑cJun↓,
*p‑p38↓,
*HO-1↑, Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin
*NADPH↑,
*GSTA1↑,
*antiOx↑, provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.
*Inflam↓,
*NQO1↑, Topical application of TQ (5 lmol) significantly increased the expression of HO-1 (Fig. 4A), NQO1 (Fig. 4B), GCL (Fig. 4C) and GST (Fig. 4D) in mouse epidermal tissue
*GCLC↑,
*GSTA1↑,

3431-

TQ,

PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer

in-vitro,

CRC,

HCT116

21.71 µM

in-vitro,

CRC,

SW48

20.53 µM

Glycolysis↓, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines.
Warburg↓,
HK2↓, was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2),
ATP↓, such reduction in glucose fermentation capacity also led to a significant reduction in overall ATP production as well as maintaining the redox state (NADPH production) of these cells
NADPH↓, showed a significant reduction in glucose fermentation, ATP and NADPH production rates
PI3K↓, reduction in HK2 levels upon TQ treatment coincided with significant inhibition in PI3K-AKT activation
Akt↓,
TumCP↓, Thymoquinone Inhibits Cell Migration and Invasion via Modulating Glucose Metabolic Reprogramming
E-cadherin↑, TQ was able to induce E-cadherin while inhibiting N-cadherin expression
N-cadherin↓,
Hif1a↓, TQ is reported to induce cell death in renal cell carcinoma [81] and pancreatic cancers [82] via inhibiting HIF1α and pyruvate kinase M2 (PKM2)-mediated glycolysis
PKM2↓,
GlucoseCon↓, TQ treatment inhibited the glucose uptake and subsequent lactate production in HCT116 and SW480 cells
lactateProd↓,
EMT↓, TQ inhibits cell proliferation, clonogenicity and epithelial-mesenchymal transition (EMT) in CRC cells (HCT116 and SW480)

3430-

TQ,

Targeting microRNAs with thymoquinone: a new approach for cancer therapy

Review,

Var,

miR-29b↑, TQ (15 mg/kg of mouse body weight) through up-regulating miR-29b expression could obstruct the Specificity protein 1 (Sp1)- NF-κB feedback loop in mice bearing leukemia and eventually reduced the rate of tumor growth
Sp1/3/4↓,
TumCG↓,
Rac1↓, TQ could exert its own anti-proliferative effects on breast cancer cells via significant up-regulation of miR-32a by which expression of Rac1 was diminished in both in vitro (1 μg/mL) and in vivo (5 mg/kg of body weight) approaches [
angioG↓, TQ has presented favorable features as an inhibitor of angiogenesis and metastasis processes
TumMeta↓,

3429-

TQ,

Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA hypermethylation reversal in leukemia cells

in-vitro,

ALL,

in-vivo,

NA,

mouse

DNMT1↓, Further, exposure of leukemia cell lines and patient primary cells to TQ resulted in DNMT1 downregulation, mechanistically, through dissociation of Sp1/NFkB complex from DNMT1 promoter.
Sp1/3/4↓,
NF-kB↓,
Apoptosis↑, led to a reduction of DNA methylation, a decrease of colony formation and an increase of cell apoptosis via the activation of caspases.
Casp↑,
Bcl-xL↓, been shown to downregulate the expression of Bcl-xL [18], COX-2 [19], iNOS [20], 5-LOX [21], TNF [22] and cyclin D1 [16]
COX2↓,
iNOS↓,
5LO↓,
TNF-α↓,
cycD1↓,
BioAv↝, The stability data revealed that the compound was stable at −20°C under dim light condition, but not at 25°C and 37°C. Thus, TQ is more stable in the dark and at cold temperature.
TumCG↓, TQ administration attenuates leukemia growth in mice

3427-

TQ,

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models

3426-

TQ,

Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms

in-vitro,

BC,

MDA-MB-468

in-vitro,

ALL,

24 h with 20 µM of TQ

UHRF1↓, (UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, and KMT2A,B,C,D,E, were downregulated in TQ-treated Jurkat cells
DNMT1↓,
DNMT3A↓,
DNMTs↓,
HDAC1↓,
HDAC4↓,
HDAC↓,
DLC1↑, several TSGs, such as DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4, and DDIT3, known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated,
PPARγ↑,
FOXO↑,
TET2↑,
CYP1B1↑,
G9a↓, expression of UHRF1, DNMT1, G9a, and HDAC1 genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose

3425-

TQ,

Advances in research on the relationship between thymoquinone and pancreatic cancer

Apoptosis↑, TQ can inhibit cell proliferation, promote cancer cell apoptosis, inhibit cell invasion and metastasis, enhance chemotherapeutic sensitivity, inhibit angiogenesis, and exert anti-inflammatory effects.
TumCP↓,
TumCI↓,
TumMeta↓,
ChemoSen↑,
angioG↓,
Inflam↓,
NF-kB↓, These anticancer effects predominantly involve the nuclear factor (NF)-κB, phosphoinositide 3 kinase (PI3K)/Akt, Notch, transforming growth factor (TGF)-β, c-Jun N-terminal kinase (JNK)
PI3K↓,
Akt↓,
TGF-β↓,
Jun↓,
p38↑, and p38 mitogen-activated protein kinase (MAPK) signaling pathways as well as the regulation of the cell cycle, matrix metallopeptidase (MMP)-9 expression, and pyruvate kinase isozyme type M2 (PKM2) activity.
MAPK↑, activation of the JNK and p38 MAPK
MMP9↓,
PKM2↓, decrease in PKM2 activity
ROS↑, ROS-mediated activation
JNK↑, activation of the JNK and p38 MAPK
MUC4↓, downregulation of MUC4;
TGF-β↑, TQ led to the activation of the TGF-β pathway and subsequent downregulation of MUC4
Dose↝, Q acts as an antioxidant (free radical scavenger) at low concentrations and as a pro-oxidant at high concentrations.
FAK↓, TQ can inhibit several key molecules such as FAK, Akt, NF-κB, and MMP-9 and that these molecules interact in a cascade to affect the metastasis of pancreatic cancer
NOTCH↓, TQ involved in increasing chemosensitivity consist of blocking the Notch1/PTEN, PI3K/Akt/mTOR, and NF-κB signaling pathways, reducing PKM2 expression, and inhibiting the Warburg effect.
PTEN↑, it also restored the PTEN protein that had been inhibited by GEM
mTOR↓,
Warburg↓, reducing PKM2 expression, and inhibiting the Warburg effect.
XIAP↓,
COX2↓,
Casp9↑,
Ki-67↓,
CD34↓,
VEGF↓,
MCP1↓,
survivin↓,
Cyt‑c↑,
Casp3↑,
H4↑,
HDAC↓,

3424-

TQ,

Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex

Review,

Var,

DNMT1↓, In this review, we highlight TQ as a potential multitarget single epidrug that functions by targeting the UHRF1/DNMT1/HDAC1/G9a complex
HDAC1↓,
TumCCA↑, inhibition of cell division, promotion of cell cycle arrest, activation of ROS production, induction of apoptosis and inhibition of tumor angiogenesis and metastasis
ROS↑,
Apoptosis↑,
angioG↓,
TumMeta↓,
selectivity↑, When compared to its effects on cancer cells, TQ has no or only mild cytotoxic effects on matched normal cells, such as normal human fibroblast cells [
BioAv↓, poor pharmacokinetics and chemical stability of TQ
BioAv↓, TQ is heat and light-sensitive, and it has poor solubility in aqueous media, which affects its biodistribution
HDAC1↓, T-ALL TQ decreased in the expression of HDAC1, 4 and 9
HDAC4↓,
UHRF1↓, TQ induces auto-ubiquitination of UHRF1 and subsequent degradation in cancer cells [23] by targeting its RING domain, which is the only domain of the UHRF1 structure that exhibits enzymatic activity
selectivity↑, via a specific inhibition of UHRF1 expression levels in cancer cells without affecting its expression in normal human cells.
G9a↓, TQ could quite possibly inhibit G9a and/or delocalize it from chromatin through its effects on UHRF1.

3422-

TQ,

Thymoquinone, as a Novel Therapeutic Candidate of Cancers

Review,

Var,

selectivity↑, TQ selectively inhibits the cancer cells’ proliferation in leukemia [9], breast [10], lungs [11], larynx [12], colon [13,14], and osteosarcoma [15]. However, there is no effect against healthy cells
P53↑, It also re-expressed tumor suppressor genes (TSG), such as p53 and Phosphatase and tensin homolog (PTEN) in lung cancer
PTEN↑,
NF-kB↓, antitumor properties by regulating different targets, such as nuclear factor kappa B (NF-Kb), peroxisome proliferator-activated receptor-γ (PPARγ), and c-Myc [1], which resulted in caspases protein activation
PPARγ↓,
cMyc↓,
Casp↑,
*BioAv↓, Due to hydrophobicity, there are limitations in the bioavailability and drug formation of TQ.
BioAv↝, TQ is sensitive to light; a short period of exposure results in severe degradation, regardless of the solution’s acidity and solvent type [27]. It is also unstable in alkaline solutions because TQ’s stability decreases with rising pH
eff↑, Encapsulating TQ with CS improves the uptake and bioavailability of TQ but has low encapsulation efficiency (35%)
survivin↓, TQ showed antiproliferative and pro-apoptotic potency on breast cancer through the suppression of anti-apoptotic proteins, such as survivin, Bcl-xL, and Bcl-2
Bcl-xL↓,
Bcl-2↓,
Akt↓, treating doxorubicin-resistant MCF-7/DOX cells with TQ inhibited Akt and Bcl2 phosphorylation and increased the expression of PTEN and apoptotic regulators such as Bax, cleaved PARP, cleaved caspases, p53, and p21 [
BAX↑,
cl‑PARP↑,
CXCR4↓, inhibited metastasis with significant inhibition of chemokine receptor Type 4 (CXCR4), which is considered a poor prognosis indicator, matrix metallopeptidase 9 (MMP9), vascular endothelial growth factor Receptor 2 (VEGFR2), Ki67, and COX2
MMP9↓,
VEGFR2↓,
Ki-67↓,
COX2↓,
JAK2↓, TQ at 25, 50 and 75 µM inhibited JAK2 and c-Src activity and induced apoptosis by inhibiting the phosphorylation of STAT3 and STAT3 downstream genes, such as Bcl-2, cyclin D, survivin, and VEGF, and upregulating caspases-3, caspases-7, and caspases-9
cSrc↓,
Apoptosis↑,
p‑STAT3↓,
cycD1↓,
Casp3↑,
Casp7↑,
Casp9↑,
N-cadherin↓, downregulated the mesenchymal genes expression N-cadherin, vimentin, and TWIST, while upregulating epithelial genes like E-cadherin and cytokeratin-19.
Vim↓,
Twist↓,
E-cadherin↑,
ChemoSen↑, The combined treatment of 5 μM TQ and 2 μg/mL cisplatin was more effective in cancer growth and progression than either agent alone in a xenograft tumor mouse model.
eff↑, TQ–artemisinin hybrid therapy (2.6 μM) showed an enhanced ROS generation level and concomitant DNA damage induction in human colon cancer cells, while not affecting nonmalignant colon epithelial at 100 μM
EMT↓, TQ inhibits the survival signaling pathways to reduce carcinogenesis progress rate, and decreases cancer metastasis through regulation of epithelial to mesenchymal transition (EMT).
ROS↑, Apoptosis is induced by TQ in cancer cells through producing ROS, demethylating and re-expressing the TSG
DNMT1↓, inhibits DNMT1, figure 2
eff↑, TQ–vitamin D3 combination significantly reduced pro-cancerous molecules (Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF and HSP-90) a
EZH2↓, reduced angiogenesis by downregulating significant angiogenic genes such as versican (VCAN), the growth factor receptor-binding protein 2 (Grb2), and enhancer of zeste homolog 2 (EZH2), which participates in histone methylatio
hepatoP↑, Moreover, TQ improved liver function as well as reduced hepatocellular carcinoma progression
Zeb1↓, TQ decreases the Twist1 and Zeb1 promoter activities,
RadioS↑, TQ combined with radiation inhibited proliferation and induced apoptosis more than a TQ–cisplatin combination against SCC25 and CAL27 cell lines
HDAC↓, TQ has inhibited the histone deacetylase (HDAC) enzyme and reduced its total activity.
HDAC1↓, as well as decreasing the expression of HDAC1, HDAC2, and HDAC3 by 40–60%
HDAC2↓,
HDAC3↓,
*NAD↑, In non-cancer cells, TQ can increase cellular NAD+
*SIRT1↑, An increase in the levels of intracellular NAD+ led to the activation of the SIRT1-dependent metabolic pathways
SIRT1↓, On the other hand, TQ induced apoptosis by downregulating SIRT1 and upregulating p73 in the T cell leukemia Jurkat cell line
*Inflam↓, TQ treatment of male Sprague–Dawley rats has reduced the inflammatory markers (CRP, TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10 and IL-4) triggered by sodium nitrite
*CRP↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*eff↑, The TQ–piperin combination has also decreased the oxidative damage triggered by microcystin in liver tissue and reduced malondialdehyde (MDA) and NO, while inducing glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathi
*MDA↓,
*NO↓,
*GSH↑,
*SOD↑,
*Catalase↑,
*GPx↑,
PI3K↓, repressing the activation of vital pathways, such as JAK/STAT and PI3K/AKT/mTOR.
mTOR↓,

3421-

TQ,

Insights into the molecular interactions of thymoquinone with histone deacetylase: evaluation of the therapeutic intervention potential against breast cancer

Analysis,

Nor,

in-vivo,

Nor,

in-vitro,

BC,

MCF-7

in-vitro,

Nor,

HaCaT

HDAC↓, The in silico findings were corroborated with an in vitro analysis, demonstrating the efficient role of TQ in the attenuation of global HDAC activity.
P21↑, reactivation of HDAC target genes (p21 and Maspin), induction of the pro-apoptotic gene Bax, down regulation of the anti-apoptotic gene Bcl-2 and arrest of the cell cycle at the G2/M phase.
Maspin↑,
BAX↑,
B2M↓,
TumCCA↑,
selectivity↑, higher cytotoxicity of TQ towards MCF-7 breast cancer cells in comparison to normal cells indicates the potential of TQ to be an anticancer drug.
*toxicity↓, Fortunately, in the case of normal cells, TQ elicits no lethal effect as that of TSA and almost all cells remained viable even at 100 μM TQ. above findings it is evident that TQ is non-toxic to normal cells
TumCMig↓, TQ inhibits migration and proliferation of breast cancer cells.
TumCP↓,

3420-

TQ,

Thymoquinone alleviates the accumulation of ROS and pyroptosis and promotes perforator skin flap survival through SIRT1/NF-κB pathway

in-vitro,

Nor,

HUVECs

in-vitro,

NA,

rat

*NF-kB↓, TQ improves perforator flap survival by inhibiting the NF-κB/NLRP3 pathway and promoting angiogenesis.
*NLRP3↓,
*angioG↑,
*MMP9↑, TQ treatment increased the levels of Cadherin-5, MMP9, and VEGF
*VEGF↑,
*OS↑, TQ enhances the survival rate and angiogenesis of multi-regional perforator flaps.
*Pyro?, TQ inhibits pyroptosis after ischemia-reperfusion injury in rat perforator flaps
*ROS↓, TQ ameliorates oxidative stress and apoptosis following ischemia-reperfusion injury in rat perforator flaps
*Apoptosis↓,
*SIRT1↑, Western blot analysis revealed that SIRT1 protein expression increased after TQ treatment,
*SOD1↑, TQ treatment increased the protein expression levels of SOD1, HO1, and eNOS in rat perforator flap tissues, t
*HO-1↑,
*eNOS↑,
*ASC?, In our current experiments, we found that TQ reduced the expression of NLRP3, GSDMD-N, Caspase-1, IL-1β, IL-18, and ASC proteins both in vivo and in vitro.
*Casp1↓,
*IL1β↓,
*IL18↓,

3419-

TQ,

Thymoquinone, a Novel Multi-Strike Inhibitor of Pro-Tumorigenic Breast Cancer (BC) Markers: CALR, NLRP3 Pathway and sPD-L1 in PBMCs of HR+ and TNBC Patients

in-vitro,

BC,

PBMCs isolated from HR+ BC patients were treated with increasing concentrations of TQ (20, 50, and 100 µM) for 24, 48, and 72 h.

 peripheral blood mononuclear cells (PBMCs)

*NLRP3↓, TQ caused a non-significant impact on NLRP3 expression at 20 µM; then, a significant increase was noticed at 50 µM (**** p < 0.0001), followed by a complete abolishment in its expression at 100 µM
*IL1β↓, TQ significantly downregulated the expression of CALR, NLRP3 components and IL-1β together with the protein levels of secreted IL-1β and sPD-L1.
*Casp1?, TQ Significantly Inhibited Caspase-1 after 24, 48, and 72 h of Treatment in PBMCs of HR+ BC Patients

3418-

TQ,

Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome

in-vitro,

Melanoma,

A375

in-vivo,

NA,

B16F10) melanoma cell line

TumMeta↓, Thymoquinone causes inhibition of metastasis in vivo
TumCMig↓, Thymoquinone causes inhibition of migration by activation of NLRP3 inflammasome.
NLRP3↓,
Casp1↓, Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18.
IL1β↓,
IL18↓,
ROS↓, Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome.
NF-kB↓, as well as inhibition of NF-κB, and hence suppressing growth and migration of melanoma cells.

3417-

TQ,

Antiproliferative Effects of Thymoquinone in MCF-7 Breast and HepG2 Liver Cancer Cells: Possible Role of Ceramide and ER Stress

in-vitro,

BC,

MCF-7

in-vitro,

Liver,

HepG2

TumCP↓, Antiproliferative effect was exerted in cancer cells via TQ incubation at different doses and durations
NF-kB↓, TQ significantly decreased cell viability, S1P, C1P, NF-κB1 mRNA and NF-κB p65 protein levels in cancer cells compared to controls.
cl‑Casp3↑, cleaved caspase-3 levels in cancer cells treated with TQ. GRP78 mRNA and protein levels also increased in cancer cells treated with TQ
GRP78/BiP↑,
ER Stress↑, TQ-induced ceramide accumulation and ER stress in conjunction with decreased S1P, C1P and NF-κB mediated cell survival may promote cancer cell death by triggering apoptosis.
Apoptosis↑,

3416-

TQ,

Thymoquinone induces apoptosis in bladder cancer cell via endoplasmic reticulum stress-dependent mitochondrial pathway

in-vitro,

Bladder,

T24

 TQ (20–100 μM) for 24 h

in-vitro,

Bladder,

253J

in-vitro,

Nor,

SV-HUC-1

TumCP↓, TQ has a significant cytotoxicity on bladder cancer cells and can inhibit their proliferation and induce apoptosis.
Apoptosis↑,
ER Stress↑, The protein changes of Bcl-2, Bax, cytochrome c and endoplasmic reticulum stress-related proteins (GRP78, CHOP, and caspase-12) revealed that the anticancer effect of TQ was associated with mitochondrial dysfunction and the endoplasmic reticulum stre
cl‑Casp3↑, TQ increased the cleaved subunits of caspase-3, caspase-8, caspase-7 and PARP (Fig. 2B) and increased caspase-3 activity (Fig. 2C) in a dose-dependent manner.
cl‑Casp8↑,
cl‑Casp7↑,
cl‑PARP↑,
Cyt‑c↑, can increase the release of cytochrome c
PERK↑, TQ increased the expression of PERK, IRE1 and ATF6 and the expression of downstream molecules such as p-eIF2a and ATF4 in a dose-dependent manner
IRE1↑,
ATF6↑,
p‑eIF2α↑,
ATF4↑,
GRP78/BiP↑, GRP78, IRE1, ATF6, ATF4 and CHOP was significantly increased after TQ treatment
CHOP↑,

1936-

TQ,

Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line

in-vitro,

Ovarian,

CaOV3

6ug/mL

in-vitro,

Nor,

WRL68

selectivity↑, TQ induces anti-proliferative activity on Caov-3 with an IC50 of 6.0±0.03 μg/mL, without any cytotoxic activity towards WRL-68 normal hepatocytes.
TumCP↓,
MMP↓, TQ induces decreases in plasma membrane permeability and mitochondrial membrane potential.
Bcl-2↓, significant decrease is observed in Bcl-2 while Bax is down-regulated.
BAX↑,
ROS↑, TQ induced anti-cancer effect involves intrinsic pathway of apoptosis and cellular oxidative stress

2096-

TQ,

Effect of total hydroalcholic extract of Nigella sativa and its n-hexane and ethyl acetate fractions on ACHN and GP-293 cell lines

in-vitro,

Nor,

GP-293

in-vitro,

Kidney,

ACHN

selectivity↑, The effect of the total extract in inducing apoptosis after 48 hours in the ACHN cell line was greater than in GP-293
eff↝, results of this study showed that the effect of the ethyl acetate fraction, which consists of semipolar compounds,16 is higher than the n-hexane fraction, which has nonpolar compounds such as fats and lipids.

2095-

TQ,

Review on the Potential Therapeutic Roles of Nigella sativa in the Treatment of Patients with Cancer: Involvement of Apoptosis

Review,

Var,

TumCCA↑, cell cycle arrest, apoptosis induction, ROS generation
Apoptosis↑,
ROS↑,
Cyt‑c↑, release of mitochondrial cytochrome C, an increase in the Bax/Bcl-2 ratio, activations of caspases-3, -9 and -8, cleavage of PARP
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
cl‑PARP↑,
P53↑, increased expressions of p53 and p21,
P21↑,
cMyc↓, decreased expressions of oncoproteins (c-Myc), human telomerase reverse transcriptase (hTERT), cyclin D1, and cyclin-dependent kinase-4 (CDK-4).
hTERT↓,
cycD1↓,
CDK4↓,
NF-kB↓, inhibited NF-κB activation
IAP1↓, (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc), and angiogenic (matrix metalloproteinase-9 and vascular endothelial growth factor)
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
COX2↓,
MMP9↓,
VEGF↓,
eff↑, combination of TQ and cisplatin in the treatment of lung cancer in a mouse xenograft model showed that TQ was able to inhibit cell proliferation (nearly 90%), reduce cell viability, induce apoptosis, and reduce tumor volume and tumor weight

2094-

TQ,

Cytotoxicity of Nigella sativa Extracts Against Cancer Cells: A Review of In Vitro and In Vivo Studies

Review,

Var,

ROS↑, Oxidative stress generation leading to cancer cell death
angioG↓, Suppression of angiogenesis and metastasis by inhibiting VEGF and MMPs.
TumMeta↓,
VEGF↓,
MMPs↓,
P53↑, upregulation of p53, Bax, caspases
BAX↑,
Casp↑,
Bcl-2↓, downregulating anti-apoptotic factors (Bcl-2, survivin).
survivin↓,
*ROS↓, antioxidant activity neutralizes reactive oxygen species (ROS)
ChemoSen↑, enhances the efficacy of conventional chemotherapeutics like doxorubicin, cisplatin, and 5-fluorouracil while reducing their toxicity.
chemoP↑,
MDR1↓, helps overcome drug resistance by modulating multidrug resistance (MDR) proteins
BioAv↓, thymoquinone, their absorption and stability are limited due to poor solubility and rapid metabolism
BioAv↑, To improve efficacy, nanoformulations, such as lipid-based carriers and nanoparticles, have been explored

2093-

TQ,

Regulation of NF-κB Expression by Thymoquinone; A Role in Regulating Pro-Inflammatory Cytokines and Programmed Cell Death in Hepatic Cancer Cells

in-vitro,

Liver,

HepG2

TQ (125–1000 ug/mL).

in-vitro,

Nor,

TumCD↑, evidence of the cytotoxic effects of TQ on HepG2 cells
selectivity↑, These findings indicate the selective regulation of HepG2 cell proliferation by TQ treatment without the detectable toxic effect of the normal hepatocytes
Casp3↑, TQ mediates the activation of Casp3, DLC1, and NF-κB, providing a new function of TQ in treating hepatocellular carcinoma (HCC).
DLC1↑,
NF-kB↑,
LDH↑, relative LDH production increased significantly in HepG2 cells treated with 500 ug/m
*toxicity↓, normal hepatocyte cells showed negligible differentiation in cell viability rate

2092-

TQ,

Dissecting the Potential Roles of Nigella sativa and Its Constituent Thymoquinone on the Prevention and on the Progression of Alzheimer's Disease

Review,

AD,

*iNOS↓, PC12normal: downregulated the iNOS expression along with NO level; (5) had a protective role of intracellular oxidative stress, by restoring the ROS level
*ROS↓,
*GSH↑, SH-SY5Y(normal): increasing the GSH levels.
*neuroP↑, TQ was able to reduce the neurotoxicity induced by Aß in an in vitro model of undifferentiated pheochromocytoma rat cell line, PC-12,
*MMPs↓, reestablishment of the abnormal levels of Matrix metalloproteinases (MMPs) and ROS
*MMP↑, E18, through the inhibition of ROS formation, and mitochondrial membrane depolarization.
*TXNIP↓, TQ was able to downregulate ... Thioredoxin-interacting protein (Txnip) and to upregulate the expression of Peroxiredoxin 1 (Prdx 1)
*Prx↑,
*memory↑, Bargi et al. (2017), reported that TQ was able, yet at lower doses, to improve memory impairments induced by LPS in rats.
*MDA↓, decreased level of markers of oxidative damage in brain tissues such as NOS, malondialdehyde (MDA) as well as an increased activity of SOD and catalase in hippocampus and cortex
*SOD↑,
*Catalase↑,
*BioAv↑, nanoemulsion may enhance the oral bioavailability and brain delivery.

2091-

TQ,

Determination of anti-cancer effects of Nigella sativa seed oil on MCF7 breast and AGS gastric cancer cells

in-vitro,

BC,

MCF-7

in-vitro,

GC,

AGS

Dose↝, The doses of 100 and 200 µg/mL were shown to be the most effective on both cancer cells
Casp3↑, N. sativa oil extract increased caspase-3 levels in both cell lines at higher concentrations and suppressed BCL2/Bax levels
Bcl-2↓,
MMP2↓, N. sativa caused a significant decrease in the expression of MMP2-9 and HSP60-70 genes over time, particularly at a dosage of 200 µg/mL compared to the control group
MMP9↓,
HSP70/HSPA5↓,

2090-

TQ,

Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

Review,

Var,

AntiCan↑, has been found to exhibit anticancer effects in numerous preclinical studies
ChemoSen↑, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy)
RadioS↑,
chemoP↑, and simultaneously minimize therapy-associated toxic effects in normal cells
radioP↑,

2089-

TQ,

Modulation of Hydrogen Peroxide-Induced Oxidative Stress in Human Neuronal Cells by Thymoquinone-Rich Fraction and Thymoquinone via Transcriptomic Regulation of Antioxidant and Apoptotic Signaling Genes

in-vitro,

Nor,

SH-SY5Y

*neuroP↑, neuroprotective properties of Thymoquinone-rich fraction (TQRF) and TQ against hydrogen peroxide- (H2O2-) induced neurotoxicity in differentiated human SH-SY5Y cells were investigated.
*ROS↓, reducing intracellular ROS levels
*SOD1↑, upregulated SOD1 and catalase gene
*Catalase↑,

2088-

TQ,

Nigella sativa L. and Its Bioactive Constituents as Hepatoprotectant: A Review

Review,

Nor,

*hepatoP↑, TQ, THY and alpha-hederin (α-hederin) provide protection to liver
*lipid-P↓, inhibition of iron-dependent lipid peroxidation
*Thiols↑, elevation in total thiol content and (GSH) level,
*ROS↓, radical scavenging,
*Catalase↑, increasing the activity of quinone reductase, catalase, superoxide dismutase (SOD) and glutathione transferase (GST), inhibition of NF-κB activity
*SOD↑,
*GSTs↑,
*NF-kB↓,
*COX2↓, inhibition of both (COX) and (LOX) protects liver from injuries
*LOX1↓,

2087-

TQ,

Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats

in-vivo,

Nor,

rats

*LDL↓, Plasma total cholesterol and low-density-lipoprotein cholesterol levels were significantly decreased in the TQRF- and TQ-treated rats compared to untreated rats.
*SOD1↑, TQRF and TQ caused the up-regulation of the superoxide dismutase 1 (SOD1), catalase, and glutathione peroxidase 2 (GPX) genes compared to untreated rats
*Catalase↑,
*GPx↑,
*antiOx↑, enhanced the expression of liver antioxidant genes of hypercholesterolemic rats.

2086-

TQ,

Cardioprotective effects of Nigella sativa oil on cyclosporine A-induced cardiotoxicity in rats

in-vivo,

Nor,

 N. sativa oil (21 days, 2 ml/kg, orally)

24 male Wistar albino young healthy rats (8-12 weeks) weighing 150-200 g

*SOD↑, Nigella sativa oil treatment caused an increase in the activities of SOD, CAT and GSH-Px compared to the control group
*Catalase↑,
*GSH↑,
*cardioP↑, N. sativa oil reduced the subsequent cyclosporine A injury in rat heart, demonstrated by normalized cardiac histopathology, decrease in lipid peroxidation, improvement in antioxidant enzyme status and cellular protein oxidation
*lipid-P↓,

2085-

TQ,

Anticancer Activities of Nigella Sativa (Black Cumin)

Review,

Var,

MMP↓, TQ induces apoptosis, disrupts mitochondrial membrane potential and triggers the activation of caspases 8, 9 and 3 in HL-60 cells.
Casp3↑,
Casp8↑,
Casp9↓,
cl‑PARP↑, PARP cleavage and the release of cytochrome c from mitochondria into the cytoplasm.
Cyt‑c↑,
Bax:Bcl2↑, marked increase in Bax/Bcl2 ratios
NF-kB↓, TQ also down-regulates the expression of NF-kappa B-regulated antiapoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin) gene products
IAP1↓,
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
cJun↑, TQ inducing apoptosis by the activation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase pathways in pancreatic cancer cell.
p38↑,
Akt↑, TQ effectively inhibited human umbilical vein endothelial cell migration, invasion, and tube formation by suppressing the activation of AKT
chemoP↑, TQ can lower the toxicity of other anticancer drugs (for example, cyclophosphamide) by an up-regulation of antioxidant mechanisms, indicating a potential clinical application for these agents to minimize the toxic effects of treatment with anticancer
radioP↑, Cemek et al. (2006) showed that N. sativa and glutathione treatment significantly antagonize the effects of radiation. Therefore, N. sativa may be a beneficial agent in protection against ionizing radiation-related tissue injury.

2084-

TQ,

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation

Review,

Var,

*ROS↓, An interesting study reported that thymoquinone is actually a potent apoptosis inducer in cancer cells, but it exerts antiapoptotic effect through attenuating oxidative stress in other types of cell injury
*chemoP↑, antioxidant activity of thymoquinone is responsible for its chemopreventive activities
ROS↑, other studies reported thymoquinone induce apoptosis in cancer cells by exerting oxidative damage
ROS⇅, Another hypothesis states that thymoquinone acts as an antioxidant at lower concentrations and a prooxidant at higher concentrations
MUC4↓, Torres et al. [17] revealed that thymoquinone down-regulates glycoprotein mucin 4 (MUC4)
selectivity↑, thymoquinone was found to inhibit DNA synthesis, proliferation, and viability of cancerous cells, such as LNCaP, C4-B, DU145, and PC-3, but not noncancerous BPH-1 prostate epithelial cells [20].
AR↓, Down-regulation of androgen receptor (AR) and cell proliferation regulator E2F-1 was indicated as the mechanism behind thymoquinone’s action in prostate cancer
cycD1↓, expression of STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1 and vascular endothelial growth factor (VEGF), was inhibited by thymoquinone, which ultimately increased apoptosis and killed cancer cells
Bcl-2↓,
Bcl-xL↓,
survivin↓,
Mcl-1↓,
VEGF↓,
cl‑PARP↑, induction of the cleavage of poly-(ADP-ribose) polymerase (PARP
ROS↑, In ALL cell line CEM-ss, thymoquinone treatment generated reactive oxygen species (ROS) and HSP70
HSP70/HSPA5↑,
P53↑, thymoquinone can induce apoptosis in MCF-7 breast cancer cells via the up-regulation of p53 expression
miR-34a↑, Thymoquinone significantly increased the expression of miR-34a via p53, and down-regulated Rac1 expression
Rac1↓,
TumCCA↑, In hepatic carcinoma, thymoquinone induced cell cycle arrest and apoptosis by repressing the Notch signaling pathway
NOTCH↓,
NF-kB↓, Evidence revealed that thymoquinone suppresses tumor necrosis factor (TNF-α)-induced NF-kappa B (NF-κB) activation
IκB↓, consequently inhibits the activation of I kappa B alpha (I-κBα) kinase, I-κBα phosphorylation, I-κBα degradation, p65 phosphorylation
p‑p65↓,
IAP1↓, down-regulated the expression of NF-κB -regulated antiapoptotic gene products, like IAP1, IAP2, XIAP Bcl-2, Bcl-xL;
IAP2↑,
XIAP↓,
TNF-α↓, It also inhibited monocyte chemo-attractant protein-1 (MCP-1), TNF-α, interleukin (IL)-1β and COX-2, ultimately reducing the NF-κB activation in pancreatic ductal adenocarcinoma cells
COX2↓,
Inflam↓, indicating its role as an inhibitor of proinflammatory pathways
α-tubulin↓, Without affecting the tubulin levels in normal human fibroblast, thymoquinone induces degradation of α and β tubulin proteins in human astrocytoma U87 cells and in T lymphoblastic leukaemia Jurkat cells, and thus exerts anticancer activity
Twist↓, thymoquinone treatment inhibits TWIST1 promoter activity and decreases its expression in breast cancer cell lines; leading to the inhibition of epithelial-mesenchymal transition (EMT)
EMT↓,
mTOR↓, thymoquinone also attenuated mTOR activity, and inhibited PI3K/Akt signaling in bladder cancer
PI3K↓,
Akt↓,
BioAv↓, Thymoquinone is chemically hydrophobic, which causes its poor solubility, and thus bioavailability. bioavailability of thymoquinone was reported ~58% with a lag time of ~23 min
ChemoSen↑, Some studies revealed that thymoquinone in combination with other chemotherapeutic drugs can show better anticancer activities
BioAv↑, Thymoquinone-loaded liposomes (TQ-LP) and thymoquinone loaded in liposomes modified with Triton X-100 (XLP) with diameters of about 100 nm were found to maintain stability, improve bioavailability and maintain thymoquinone’s anticancer activity
PTEN↑, Thymoquinone also induces apoptosis by up-regulating PTEN
chemoP↑, A recent study showed that thymoquinone can potentiate the chemopreventive effect of vitamin D during the initiation phase of colon cancer in rat model
RadioS↑, thymoquinone also mediates radiosensitization and cancer chemo-radiotherapy
*Half-Life↝, Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) has been developed to improve its bioavailability (elimination half-life ~5 hours)
*BioAv↝, calculated absolute bioavailability of thymoquinone was reported ~58% with a lag time of ~23 min by Alkharfy et al.

2083-

TQ,

Thymoquinone inhibits proliferation in gastric cancer via the STAT3 pathway in vivo and in vitro

in-vitro,

GC,

HGC27

in-vitro,

GC,

BGC-823

in-vitro,

GC,

SGC-7901

in-vivo,

NA,

mouse

p‑STAT3↓, TQ inhibited the phosphorylation of STAT3
JAK2↓, reduction in JAK2 and c-Src activity
c-Src↓,
Bcl-2↓, TQ also downregulated the expression of STAT3-regulated genes, such as Bcl-2, cyclin D, survivin, and vascular endothelial growth factor
cycD1↓,
survivin↓,
VEGF↓,
Casp3?, activated caspase-3,7,9
Casp7?,
Casp9?,
*toxicity∅, A phase I study reported that in adult patients with solid tumors or hematological malignancies who were treated with TQ, there were no significant systemic toxicities[10].
TumVol↓, Thymoquinone inhibits tumor growth in a gastric mouse xenograft model.

1937-

TQ,

Migration and Proliferation Effects of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) and Thymoquinone (TQ) on In Vitro Wound Healing Models

NA,

Nor,

3T3

3-12uM

*ROS↓, In this study, TQ-NLC or TQ was seen to reduce the level of ROS produced in the cells at all concentrations of treatment given.
*antiOx↓, Both of these compounds are able to exert their antioxidant activity at the concentration as lower as 3 μM within 24 hours of treatment and as higher as 12 μM without causing any harm towards the cells.
*BioAv↓, bioavailability of TQ is limited by its poor solubility and lipophilic nature in water
*BioAv↑, to overcome the disadvantages of TQ, thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was designed and effectively prepared by Ng et al. [49] via high-pressure homogenization technique
*NO↑, TQ was also reported to decrease production of nitric oxide (NO) and attenuate nitrosative stress by inhibiting the inducible nitric oxide synthase enzyme
*SOD↑, TQ exhibits strong antioxidant activity by upregulating superoxide dismutase (SOD), glutathione (GPX), and catalase (CAT) [88].
*GPx↑,
*Catalase↑,

2097-

TQ,

Crude extract of Nigella sativa inhibits proliferation and induces apoptosis in human cervical carcinoma HeLa cells

in-vitro,

Cerv,

HeLa

 IC50 values for 25, 50, 75 and 100 ug/ml were observed after 72, 48, 24 and 24 h

Cyt‑c↑, release of mitochondrial cytochrome c, increase of Bax/Bcl-2 ratio, activation of caspases-3, -9 and -8 and cleavage of poly (ADP-ribose) polymerase (PARP).
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
Casp8↑,
cl‑PARP↑,
cMyc↓, EENS decreased expression of oncoproteins such as c-Myc, human telomerase reverse transcriptase (hTERT), cyclin D1 and cyclin-dependent kinase-4 (CDK-4), but increased expression of tumor-suppressor proteins including p53 and p21.
hTERT↓,
cycD1↓,
CDK4↓,
P53↑,
P21↑,
TumCP↓, EENS inhibits proliferation and induces apoptosis in HeLa cells
Apoptosis↓,
selectivity↑, On the other hand, they exerted marginal effect on the non-malignant human fibroblasts HF-5, which suggests that the EENS and AENS may selectively target cervical cancer cells but spare normal cell line.

1935-

TQ,

Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis

Review,

OS,

Apoptosis↑, Nigella sativa, has received considerable attention in cancer treatment owing to its distinctive properties, including apoptosis induction, cell cycle arrest, angiogenesis and metastasis inhibition, and reactive oxygen species (ROS) generation
TumCCA↑,
angioG↓,
TumMeta↓,
ROS↑,
P53↑, TQ upregulated the expression of p53 in a time-dependent manner, promoting apoptosis in MCF-7
Twist↓, TQ to BT 549 cell lines (breast cancer cells) in a dose-dependent fashion reduced the transcription activity of TWIST1, one of the promotors of endothelial-to-mesenchymal transition (EMT)
E-cadherin↑, TQ engagement increased the expression of E-cadherin and decreased the expression of N-cadherin
N-cadherin↓,
NF-kB↓, fig 1
IL8↓,
XIAP↓,
Bcl-2↓,
STAT3↓,
MAPK↓,
PI3K↓,
Akt↓,
ERK↓,
MMP2↓,
MMP9↓,
*ROS↓, prevent cancer formation
HO-1↑, Moreover, TQ could stunt the growth of HCC cell lines through the generation of ROS, heme oxygenase-1 (HO-1)
selectivity↑, application of phytochemicals such as TQ is a promising strategy since these compounds show less toxicity against normal cells.
TumCG↓, Despite inhibiting the growth and viability of different cancer types, TQ has no adverse effects on healthy cells

1934-

TQ,

Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species

in-vitro,

Pca,

PC3

25-150um/L

80uM

in-vitro,

Pca,

C4-2B

50uM

ROS↑, A dose-dependent increase in ROS generation was clearly evident at this time point. Almost a 3.25-fold increase in ROS levels were observed with 75 and 100 umol/L of TQ in both PC-3 and C4-2B cells.
GSH↓, GSH levels were significantly decreased by 50 and 100 umol/L TQ, showing 35% and 65% reductions in GSH levels
eff↓, Pretreatment with NAC protected PC-3 and C4-2B cells against TQ-induced ROS generation and growth inhibition

1933-

TQ,

Thymoquinone: potential cure for inflammatory disorders and cancer

Review,

Var,

antiOx↑, Its anti-oxidant/anti-inflammatory effect has been reported in various disease models. Potent free radical and superoxide radical scavenger at both nanomolar and micromolar range, respectively
Inflam↓,
AntiCan↑, anticancer effect(s) of thymoquinone are mediated through different modes of action, including anti-proliferation, apoptosis induction, cell cycle arrest, ROS generation and anti-metastasis/anti-angiogenesis.
TumCCA↑, Thymoquinone was also shown to induce G0/G1 arrest
ROS↑, activation of caspases and generation of ROS.
angioG↓,
Apoptosis↑,
Casp↑,
eff↑, combination of thymoquinone and conventional chemotherapeutic drugs could produce greater therapeutic effect as well as reduce the toxicity of the latter
eff↝, TQ has been reported to exert anti-oxidant activity at lower concentration, but at higher concentration, it showed significant pro-oxidant effects. Whether TQ can act as a pro-oxidant or antioxidant can also be attributed cell type

1932-

TQ,

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

Review,

Var,

ROS↑, most quoted reports indicate in increase in ROS

1931-

TQ,

doxoR,

Thymoquinone enhances the anticancer activity of doxorubicin against adult T-cell leukemia in vitro and in vivo through ROS-dependent mechanisms

in-vivo,

AML,

Dox  50-750 nM, TQ 5-40uM

mice

eff↑, Q and Dox caused greater inhibition of cell viability and increased sub-G1 cells in both cell lines compared to Dox or TQ alone.
tumCV↓,
TumCCA↑,
ROS↑, combination induced apoptosis by increasing ROS and causing disruption of mitochondrial membrane potential.
MMP↓,
eff↑, Pretreatment with N-acetyl cysteine (NAC) or pan caspase inhibitor significantly inhibited the apoptotic response suggesting that cell death is ROS- and caspase-dependent.
TumVol↓, combination reduced tumor volume in NOD/SCID mice
eff↑, possibility to use up to twofold lower doses of Dox against ATL while exhibiting the same cancer inhibitory effects.
Ki-67↓, However, in TQ and combination treated groups, the expression of Ki-67 was significantly lower

1930-

TQ,

Therapeutic implications and clinical manifestations of thymoquinone

Review,

Var,

AntiCan↑, TQ showed anti-cancer, anti-oxidant, and anti-inflammatory properties, validated in various disease models.
antiOx↑,
Inflam↓,
TumCP↓, anti-cancer potential of TQ is goverened by anti-proliferation, cell cycle arrest, apoptosis induction, ROS production, anti-metastasis and anti-angiogenesis, inhibition of cell migration and invasion action
TumCCA↑,
Apoptosis↑,
ROS↑,
TumMeta↓,
TumCI↓,

1929-

TQ,

Thymoquinone Suppresses the Proliferation, Migration and Invasiveness through Regulating ROS, Autophagic Flux and miR-877-5p in Human Bladder Carcinoma Cells

in-vitro,

Bladder,

5637

0-50uM

 75 µM

in-vitro,

Bladder,

T24

60 µM

tumCV↓, TQ restrains the viability, proliferation, migration and invasion through activating caspase-dependent apoptosis in bladder carcinoma cells
TumCP↓,
TumCI↓,
Casp↑,
ROS↑, mediated by TQ induced ROS increase in bladder carcinoma cells
PD-L1↓, TQ upregulates hsa-miR-877-5p level to reduce PD-L1 expression in 5637 and T24 BC cells
EMT↓, which suppresses the epithelial mesenchymal transition (EMT)
MMP↓, MMP was markedly lowered by TQ in a dose-dependent way
eff↓, MMP was significantly recovered in the combined treatment of TQ and NAC

1928-

TQ,

Thymoquinone Crosstalks with DR5 to Sensitize TRAIL Resistance and Stimulate ROS-Mediated Cancer Apoptosis

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

TumCP↓, TQ+TRAIL significantly inhibited the protein content-based proliferation of MDA-MB-231 cells more than MCF-7 cells.
DR4↑, synergistic effect of them significantly up-regulated the genetic expressions of DR4, DR5, Cas-8, and FADD genes
DR5↑,
Casp8↑,
FADD↑,
Bcl-2↓, inhibited the genetic expression of the Bcl-2
ROS↑, The induction of the apoptotic genes using the combined therapy was stimulated by the elevation of the reactive oxygen species (ROS); nitric oxide (NO) and malondialdehyde (MDA) levels.
NO↑,
MDA↑,

1309-

TQ,

QC,

Thymoquinone and quercetin induce enhanced apoptosis in non-small cell lung cancer in combination through the Bax/Bcl2 cascade

in-vitro,

Lung,

 IC50 values of Tq and Qu alone in A549 cells were found to be 45.78 and 35.69 µM

Bcl-2↓,
BAX↑,
Apoptosis↑,

1308-

TQ,

Thymoquinone induces apoptosis via targeting the Bax/BAD and Bcl-2 pathway in breast cancer cells

in-vitro,

BC,

MCF-7

tumCV↓,
TumCP↓,
BAX↑,
P53⇅, p53 gene expression was decreased in MCF-7 cells but slightly increased in HEK293 cells
Apoptosis↑,

1138-

TQ,

Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-β/Smad2/3 signaling pathway

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

TumMeta↓,
EMT↓, thymoquinone reversed EMT
E-cadherin↑,
Vim↓,
Slug↓,
TGF-β↓,
SMAD2↓,
SMAD3↓,

1052-

TQ,

Thymoquinone Anticancer Effects Through the Upregulation of NRF2 and the Downregulation of PD-L1 in MDA-MB-231 Triple-Negative Breast Cancer Cells

in-vitro,

BC,

MDA-MB-231

TQ (0-50 µM)24hr

NRF2↑, TQ had the ability to elicit more than 2-fold increase in Nrf2 expression in IFN-γ stimulated MDA-MB-231 cells.
PD-L1↓,
Apoptosis↑,

1019-

TQ,

Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation

vitro+vivo,

CRC,

LoVo

20 μmol/L

also mice

TumCP↓, 20 μmol/L TQ significantly reduced human LoVo colon cancer cell proliferation
p‑PI3K↓,
p‑Akt↓,
p‑GSK‐3β↓,
β-catenin/ZEB1↓,
COX2↓,
PGE2↓,
EP2↓,
EP4↓,

962-

TQ,

Thymoquinone affects hypoxia-inducible factor-1α expression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways

in-vitro,

PC,

PANC1

0, 5, 10, 15, 20, 25, 30, and 35 µM

11uM

 experiments were constructed in hypoxic conditions (O2 content was 1%)

in-vitro,

Nor,

hTERT-HPNE

no effect

normal pancreatic duct epithelial (hTERT-HPNE) cells

in-vitro,

PC,

AsPC-1

11uM

in-vitro,

PC,

Bxpc-3

26uM

TumCMig↓,
TumCI↓,
Apoptosis↑, no significant effects on hTERT-HPNE cells (normal cells) ****
Hif1a↓, TQ significantly reduced the mRNA and protein expression levels of HIF-1α in PANC-1, AsPC-1, and BxPC-3 cells.
PI3k/Akt/mTOR↓,
TumCCA↑, possible mechanism of TQ's influence on PC cell cycle was that TQ inhibited the proliferation of cancer cells (reducing the proportion of S phase) and damaged the DNA of cancer cells (increasing the proportion of G2/M phase). No effect on normal cell
*toxicity↓, TQ had no significant effect on the viability of hTERT-HPNE cells
*TumCI∅, no significant difference in the invasion ability of the hTERT-HPNE cells
*TumCMig∅, no significant effect on the migration and invasion of normal pancreatic ductal epithelial cells.

2112-

TQ,

Crude flavonoid extract of the medicinal herb Nigella sativa inhibits proliferation and induces apoptosis in breastcancer cells

in-vitro,

BC,

MCF-7

45 mg/ml@72hr

Apoptosis↑, apoptosis, including cell shrinkage and detachment, nuclear condensation, and DNA damage, were observed after the CFENS treatments
DNAdam↑,
ROS↑, CFENS triggered ROS accumulation, GSH depletion, disruption of mitochondrial membrane potential, activation of caspases-3/7 and -9, and an increase in the Bax/Bcl-2 ratio in MCF-7 cell
GSH↓, GSH level is depleted, whereas GSSG is accumulated, resulting in a decrease in the GSH/GSSG ratio
MMP↓, ROS accumulation also induces outer mitochondrial membrane permeabilization (MMP), which leads to loss of mitochondrial membrane potential (ΔΨm)
Casp3↑,
Casp7↑,
Casp9↑,
Bax:Bcl2↑,
P53↑, CFENS induced cell cycle arrest, upregulated the expression levels of p53 and p21 proteins,
P21↑,
cycD1↓, downregulated the expression of cyclin D1.
GSSG↑,
GSH/GSSG↓, GSH level is depleted, whereas GSSG is accumulated, resulting in a decrease in the GSH/GSSG ratio

2127-

TQ,

Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

Review,

GBM,

chemoP↑, TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells
ChemoSen↑,
BioAv↑, TQ adds another advantage in overcoming blood-brain barrier
PTEN↑, TQ upregulates PTEN signaling [72, 73], interferes with PI3K/Akt signaling and promotes G(1) arrest, downregulates PI3K/Akt
PI3K↓,
Akt↓,
TumCCA↓,
NF-kB↓, and NF-κB and their regulated gene products, such as p-AKT, p65, XIAP, Bcl-2, COX-2, and VEGF, and attenuates mTOR activity
p‑Akt↓,
p65↓,
XIAP↓,
Bcl-2↓,
COX2↓,
VEGF↓,
mTOR↓,
RAS↓, Studies in colorectal cancer have demonstrated that TQ inhibits the Ras/Raf/MEK/ERK signaling
Raf↓,
MEK↓,
ERK↓,
MMP2↓, Multiple studies have reported that TQ downregulates FAC and reduces the secretion of MMP-2 and MMP-9 and thereby reduces GBM cells migration, adhesion, and invasion
MMP9↓,
TumCMig↓,
TumCI↓,
Casp↑, caspase activation and PARP cleavage
cl‑PARP↑,
ROS⇅, TQ is hypothesized to act as an antoxidant at lower concentrations and a prooxidant at higher concentrations depending on its environment [89]
ROS↑, In tumor cells specifically, TQ generates ROS production that leads to reduced expression of prosurvival genes, loss of mitochondrial potential,
MMP↓,
eff↑, elevated level of ROS generation and simultaneous DNA damage when treated with a combination of TQ and artemisinin
Telomerase↓, inhibition of telomerase by TQ through the formation of G-quadruplex DNA stabilizer, subsequently leads to rapid DNA damage which can eventually induce apoptosis in cancer cells specifically
DNAdam↑,
Apoptosis↑,
STAT3↓, TQ has shown to suppress STAT3 in myeloma, gastric, and colon cancer [86, 171, 172]
RadioS↑, TQ might enhance radiation therapeutic benefit by enhancing the cytotoxic efficacy of radiation through modulation of cell cycle and apoptosis [31]

2126-

TQ,

Biological and therapeutic activities of thymoquinone: Focus on the Nrf2 signaling pathway

Review,

Nor,

*antiOx↑, several biological effects, including antioxidant, antibacterial, antineoplastic, nephroprotective, hepatoprotective, gastroprotective, neuroprotective, anti-nociceptive, and anti-inflammatory activities.
*Bacteria↓,
*RenoP↑,
*hepatoP↑,
*neuroP↑,
*Inflam↓,
*Keap1↓, beneficial effects are mostly related to modulation of the Nrf2 signaling pathway by blockage of Keap1, stimulating the expression of the Nrf2 gene, and inducing the nuclear translocation of Nrf2
*NRF2↑,
*other↝, lots of references for normal cell reactions

2125-

TQ,

Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis

in-vitro,

RCC,

RCC4

in-vitro,

RCC,

Caki-1

Hif1a↓, TQ reduced HIF-1α protein levels in renal cancer cells. In addition, decreased HIF-1α levels in both cytoplasm and nucleus after treatment with 10 μM of TQ were observed in Caki-1 cells
eff↝, suggesting that suppression of HIF-1α by TQ may be connected to Hsp90-mediated HIF-1α stabilization
uPAR↓, significantly downregulated the hypoxia-induced tumor promoting HIF-1α target genes, such as FN1, LOXL2, uPAR, VEGF, CA-IX, PDK1, GLUT1, and LDHA, in TQ-treated Caki-1
VEGF↓,
CAIX↓,
PDK1↓,
GLUT1↓,
LDHA↓,
Glycolysis↓, we found that TQ significantly increases glucose levels in hypoxic Caki-1 and A498 cultured medium, indicating that hypoxia-induced anaerobic glycolysis is significantly suppressed by TQ treatment
e-lactateProd↓, Consistent with suppression of hypoxic glycolysis by TQ treatment, increased extracellular lactate levels under hypoxia were decreased in TQ-treated Caki-1 and A498 renal cancer cells
i-ATP↓, intracellular ATP levels were significantly decreased in TQ-treated Caki-1 and A498 cells under hypoxia

2124-

TQ,

Thymoquinone: an emerging natural drug with a wide range of medical applications

Review,

Var,

hepatoP↑, Hepatoprotective
Bax:Bcl2↑, A549 non-small cell lung cancer cells exposed to benzo(a)pyrene plus TQ in vitro
cycD1↓,
P21↑,
TRAIL↑,
P53↑,
TumCCA↑, G2/M cell cycle arrest
hepatoP↑, Hepatoprotective effects
*ALAT↓, The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tissue levels of malondialdehyde (MDA), oxidized glutathione (GSSG), and superoxide dismutase (SOD) activity were found to be lower
*AST↓,
*MDA↓,
*GSSG↓,
*SOD↓,
*COX2↓, N. sativa and TQ treatment also suppressed the expression of the COX-2 enzyme in the pancreatic tissue
*lipid-P↓, Thymoquinone and thymohydroquinone inhibited in vitro non-enzymatic lipid peroxidation in hippocampal homogenates induced by iron-ascorbate (52)
PPARγ↑, In breast cancer cells TQ was able to increase peroxisome proliferator-activated receptor gamma (PPAR-γ) activity
p38↑, Treatment of human breast carcinoma in both in vitro and in vivo models demonstrated antiproliferative and proapoptotic effects of TQ, which are mediated by its inductive effect on p38 and ROS signaling
ROS↑,
ChemoSen↑, TQ possesses anti-tumor effects in breast tumor xenograft mice and it potentiates the antitumor effect of doxorubicin (64).
selectivity↑, TQ is also a microtubule-targeting agent (MTA), and binds to the tubulin-microtubule network, thus preventing microtubule polymerization and causing mitotic arrest and apoptosis of A549 cells but not of normal HUVEC cells
selectivity↑, No effect on α/β tubulin protein expression was found in normal human fibroblasts used as control cell model. These data indicate that TQ exerts a selective effect on α/β tubulin in cancer cells

2123-

TQ,

Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma

in-vitro,

lymphoma,

PEL

10, 25, 50 uM @ 24h

Akt↓, TQ treatment results in down-regulation of constitutive activation of AKT via generation of reactive oxygen species (ROS)
ROS↑,
BAX↓, and it causes conformational changes in Bax protein, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol.
MMP↓,
Cyt‑c↑,
eff↑, subtoxic doses of TQ sensitized PEL cells to TRAIL via up-regulation of DR5
Casp9↑, TQ-induced signaling causes caspase-9/3 activation and PARP cleavage in PEL cells
Casp3↑,
cl‑PARP↑,
DR5↑, TQ-induced ROS generation regulates up-regulation of DR5

2122-

TQ,

Review on Molecular and Therapeutic Potential of Thymoquinone in Cancer

Review,

Var,

ChemoSen↓, Chemosensitization by TQ is mostly limited to in vitro studies, and it has potential in therapeutic strategy for cancer
*ROS↓, its scavenging ability against freeradicals, including reactive oxygen species (ROS;
*GSH↑, TQ reduces the cellular oxidative stress by inducing glutathione (GSH)
RenoP↑, TQ protects the kidney against ifosfamide, mercuric chloride, cisplatin, and doxorubicin-induced damage by preventing renal GSH depletion and antilipid peroxidation
hepatoP↑, TQ ameliorated hepatotoxicity of carbon tetrachloride as seen by the significant reduction of the elevated levels of serum enzymes and significant increase of the hepatic GSH content
COX2↓, TQ induces inhibition of PGE2 and COX-2, in a COX-2 overexpressing HPAC cells (PC cells).
NF-kB↓, NF-κB is a molecular target of TQ in cance
chemoP↑, TQ is a chemopreventive agent for prostate cancer
neuroP↑, The beneficial effect of TQ as a neuroprotective agent in inhibiting viability of human neuroblastoma cell line SH-SY5Y
TumCCA↑, TQ, it reportedly induces G1 cell cycle arrest in osteosarcoma cancer cells (COS31) as well as in human colon cancer cells (HCT-116),
P21↑, TQ caused a dramatic increase in p21WAF1 , (Cip1), and p27 (Kip1) and blocked the progression of synchronized LNCaP cells from G1 to S phase,
p27↑,
ROS↑, TQ on p53 deficient lymphoblastic leukemia Jurkat cells and found TQ treatment produced intracellular ROS pro- moting a DNA damage-related cell cycle arrest and triggered apoptosis
DNAdam↑,
MUC4↓, in pancreatic cancer cells and it was found that TQ downregulates MUC-4 expression through the proteasomal pathway

2121-

TQ,

Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: The Role of p38 MAPK and ROS

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

p‑p38↑, Here, we show that TQ induced p38 phosphorylation and ROS production in breast cancer cells
ROS↑,
TumCP↓, These inductions were found to be responsible for TQ’s anti-proliferative and pro-apoptotic effect
eff↑, TQ treatment was found to suppress the tumor growth and this effect was further enhanced by combination with doxorubicin
XIAP↓, TQ also inhibited the protein expression of anti-apoptotic genes, such as XIAP, survivin, Bcl-xL and Bcl-2, in breast cancer cells and breast tumor xenograf
survivin↓,
Bcl-xL↓,
Bcl-2↓,
Ki-67↓, Reduced Ki67 and increased TUNEL staining were observed in TQ-treated tumors
*Catalase↑, TQ was also found to increase the level of catalase, superoxide dismutase and glutathione in mouse liver tissues.
*SOD↑,
*GSH↑,
hepatoP↑,
p‑MAPK↑, TQ significantly up-regulated the phosphorylation of various MAPKs in MCF-7 cells
JNK↓, The increase of JNK and p38 protein phosphorylation was found to be maximal at 12 h
eff↓, N-acetylcysteine (NAC) prevents TQ-induced ROS production

2120-

TQ,

Thymoquinone induces apoptosis of human epidermoid carcinoma A431 cells through ROS-mediated suppression of STAT3

in-vitro,

Melanoma,

A431

ROS↑, The induction of intracellular reactive oxygen species (ROS) by TQ was evaluated by 2',7'-dichlorofluorescein diacetate staining.
Apoptosis↑, Treatment of A431 cells with TQ-induced apoptosis, which was associated with the induction of p53 and Bax, inhibition of Mdm2, Bcl-2, and Bcl-xl expression, and activation of caspase-9, -7, and -3
P53↑,
BAX↑,
MDM2↓,
Bcl-2↓,
Bcl-xL↓,
Casp9↑,
Casp7↑,
Casp3↑,
STAT3↓, Moreover, the expression of STAT3 target gene products, cyclin D1 and survivin, was attenuated by TQ treatment.
cycD1↓,
survivin↓,
eff↓, The generation of ROS was increased during TQ-induced apoptosis, and the pretreatment of N-acetyl cysteine, a ROS scavenger, reversed the apoptotic effect of TQ

2119-

TQ,

Dual properties of Nigella Sativa: anti-oxidant and pro-oxidant

Review,

Var,

*ROS↓, NS has both anti-oxidant and pro-oxidant properties in different cell types hence should be used carefully because it acts as a cytoprotective or cytotoxic agent in inflammatory and malignant conditions respectively.
ROS↑, malignant conditions
chemoP↑, It is reported that nigella can reduce the toxic effects of anticancer drugs
RenoP↑, NS has been shown to improve multiple organ toxicity in models of oxidative stress
hepatoP↑,
NLRP3↓, NLRP3 inflammasome was inactivated partially by inhibition of ROS in melanoma cells by TQ administration.
neuroP↑, NS oil has been found to be neuroprotective against oxidative stress in epileptogenesis
NF-kB↓, TQ has been shown to exhibit down regulation of NF-κB expression in lung cancer cells and in osteosarcoma cells
P21↑, TQ up regulated the expression of p21 and down regulated the histone deacetylase (HDAC) activity and induced histone hyperacetylation causing induction of apoptosis and inhibition of proliferation in pancreatic cancer cell
HDAC↓,
Apoptosis↑,
TumCP↓,
GSH↓, TQ was found to decrease glutathione (GSH) levels in prostate cancer cells resulting in up-regulated expression of GADD45 alpha
GADD45A↑,
GSK‐3β↑, TQ caused the apoptosis of tumor cells by modulation of wnt signaling through activation of GSK-3β

2118-

TQ,

Rad,

In vivo radioprotective effects of Nigella sativa L oil and reduced glutathione against irradiation-induced oxidative injury and number of peripheral blood lymphocytes in rats

in-vivo,

Nor,

rats

*ROS↓, The blood oxidative stress marker levels in irradiated rats that were pretreated with NS and GSH were significantly decreased; however, non-enzymatic antioxidant levels were significantly increased.
RenoP↑, NS and GSH may be a beneficial agent in protection against ionizing radiation-related tissue injury.
hepatoP↑,

2117-

TQ,

Effects of Nigella sativa L. on Lipid Peroxidation and Reduced Glutathione Levels in Erythrocytes of Broiler Chickens

in-vivo,

Nor,

Broiler chickens

*GSH↑, GSH levels were significantly (p<0.005) higher in 0.5 % and 1 % of Nigella sativa L. groups
*ROS↓, Nigella sativa L. caused protective effects on the oxidative stress-induced erythrocyte injury by inhibiting free radical production and regulation of GSH.

2116-

TQ,

Cisplatin,

Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

in-vivo,

Nor,

rats

*hepatoP↑, Oral administration of NSO ameliorates the hepatotoxicity induced by CP treatment.
*antiOx↑, NSO improves the endogenous antioxidant status and metabolic activity of liver.
*ROS↓, NSO protects the liver against CP generated free radical attack.
ALAT↓, CP-induced increase in ALT, AST, PLs, and Chl were prevented by NSO administration.
AST↓,

2115-

TQ,

Protective effects of Nigella sativa on gamma radiation-induced jejunal mucosal damage in rats

in-vivo,

Nor,

Thirty 12–14-week-old Male Wistar albino rats

*radioP↑, Nigella sativa has protective effects against radiation-induced damage, suggesting that clinical transfer is feasible
*MDA↓, Nigella sativa treatment significantly (p < 0.05) decreased the elevated tissue MDA levels comparison to control group and increased the reduced GSH-Px
*GSH↑,

2114-

TQ,

Anti-Aging Effect of Nigella Sativa Fixed Oil on D-Galactose-Induced Aging in Mice

in-vivo,

Nor,

0.1, 0.2 and 0.5 mL/kg

male mice for 42 days

*ALAT↓, N. sativa oil (0.1 and 0.2 mL/kg) diminished the levels of the biochemical markers ALT and AST.
*AST↓,
*lipid-P↓, Administration of black seed oil (0.1, 0.2 and 0.5 mL/kg) reduced lipid peroxidation
*GSH↑, and at doses 0.1 and 0.2 mL/kg significantly recovered the GSH content.
*Bax:Bcl2↓, The oil decreased Bax/Bcl2 levels and at 0.1 mL/kg down-regulated the expressions of caspase-3
*proCasp3↓,
*cl‑Casp3↓,
*antiOx↑, Through its antioxidant and anti-apoptosis properties, black seed oil exhibited an anti-aging effect in a model of aging induced with D-galactose.

2113-

TQ,

Potential role of Nigella sativa (NS) in abating oxidative stress-induced toxicity in rats: a possible protection mechanism

in-vivo,

Nor,

rats

*antiOx↑, NS exhibited an anti-oxidative stress effect in the liver and kidneys as indicated by the low levels of ALT and creatinine.
*RenoP↑,
*hepatoP↑, studies have suggested a hepatoprotective effect of NS
*SOD↑, increase in SOD and GSH-Px indirectly caused an alleviation of oxidative stress, leading to a much lower level of MDA.
*GSH↑, decrease in SOD and G-Px levels were observed in a very short duration (peaked at the 3rd day of administration) and decreased to normal levels immediately after this period
*ROS↓, NS at 100 mg/kg b.w/per day for three consecutive days, demonstrated the highest efficacy in abating oxidative stress in rats.
*lipid-P↓, abating oxidative stress and lipid peroxidation in NS-treated group
ALAT↓,
creat↓,

113-

TQ,

Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer

vitro+vivo,

Pca,

C4-2B

 139 uM

 C4-2B-R

HH↓,
Shh↓,
Gli1↓,

2111-

TQ,

MTX,

Effect of Nigella sativa (black seeds) against methotrexate-induced nephrotoxicity in mice

in-vivo,

Nor,

mice

*RenoP↑, NS is protective against MTX-induced nephrotoxicity.
*GSH↑, MTX has resulted in a small elevation in MDA and reduction in GSH levels in kidney homogenate which was returned back to control values when NS and MTX were administered in combination.

2110-

TQ,

Nigella sativa seed oil suppresses cell proliferation and induces ROS dependent mitochondrial apoptosis through p53 pathway in hepatocellular carcinoma cells

in-vitro,

HCC,

HepG2

50–250 μg/ml) of NSO

44.6 μg/ml

in-vitro,

BC,

MCF-7

46.2 μg/ml

in-vitro,

Lung,

A549

245 μg/ml

in-vitro,

Nor,

HEK293

1136 μg/ml

indicates selectivity

P53↑, N. sativa exerts anticancer activity by mitochondrial apoptosis via p53 pathway.
lipid-P↑, Induction of lipid peroxidation, and depletion of glutathione level were also observed.
GSH↓, decrease in the level of MMP was also observed in HepG2 cells after NSO exposure for 24 h
ROS↑, ROS generation and reduced MMP suggest role of oxidative stress in cell death.
MMP↓,
BAX↑, Upregulation of p53, Bax, caspase-3 and caspase-9 and downregulation of Bcl-2 gene
Casp3↑,
Casp9↑,
Bcl-2↓,
tumCV↓, exhibited significant decrease in the percentage cell viability of HepG2, MCF-7 and A-549 cells in a concentration-dependent manner.
selectivity↑, The IC50 values of NSO obtained by MTT assay were 46.2 μg/ml for MCF-7, 44.6 μg/ml for HepG2, 245 μg/ml for A-549 and 1136 μg/ml for HEK293(normal) cell lines

2109-

TQ,

Thymoquinone Induces Mitochondria-Mediated Apoptosis in Acute Lymphoblastic Leukaemia in Vitro

in-vitro,

ALL,

CEM

1.5 µg/mL

Apoptosis↓, TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax
Bcl-2↓,
BAX↑,
ROS↑, Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells.
HSP70/HSPA5↑,
Casp3↑,
Casp8↑,

2108-

TQ,

Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa

Review,

Var,

HDAC↓, Intraperitoneal injection of TQ (10 mg/kg) for 18 days was associated with significant 39% inhibition of LNM35 xenograft tumor growth, with a significant increase in caspase-3 activity and a significant decrease in histone deacetylase-2 (HDAC2)
TumCCA↑, TQ treatment caused a G0/G1 cell-cycle arrest due to decreased cyclin D1 level and increased expression of p16, a CDK inhibitor (Gali-Muhtasib et al., 2004b)
cycD1↓,
p16↑,
P53↑, increased expression of p53,
Bax:Bcl2↑, TQ significantly induced apoptosis in both cell lines by increasing the Bax/Bcl-2 ratio and decreasing Bcl-xL
Bcl-xL↓,
NF-kB↓, 25 mM TQ was accompanied by down-regulated expression of NF-kB-targeted anti-apoptotic factors (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin)
IAP1↓,
IAP2↓,
XIAP↓,
survivin↓,
COX2↓, and proliferative factors (cyclin D1, COX-2, and c-Myc) due to suppressed NF-kB signaling
cMyc↓,
ROS↑, TQ-induced oxidative damage,
Casp3↑, TQ-induced activation of caspase-3, poly (ADP-ribose) polymerase (PARP) cleavage, and the release of cytochrome c from mitochondria into the cytoplasm
cl‑PARP↑,
Cyt‑c↑,
STAT3↓, TQ (5-20 uM) significantly suppressed the constitutive as well as IL-6-induced STAT3, but not STAT5, activation in U266 cells and RPMI-8226 cells

2107-

TQ,

Cytotoxicity of Nigella sativa seed oil and extract against human lung cancer cell line

in-vitro,

Lung,

A549

tumCV↑, NSE and NSO significantly reduce the cell viability and alter the cellular morphology of A-549 cells in a concentration dependent manner

2106-

TQ,

Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy

Review,

Var,

Apoptosis↑, The anticancer power of TQ is accomplished by several aspects; including promotion of apoptosis, arrest of cell cycle and ROS generation.
TumCCA↑,
ROS↑,
*Catalase↑, activation of antioxidant cytoprotective enzymes including, CAT, SOD, glutathione reductase (GR) [80], glutathione-S-transferase (GST) [81] and glutathione peroxidase (GPx) - scavenging H2O2 and superoxide radicals and preventing lipid peroxidation
*SOD↑,
*GR↑,
*GSTA1↓,
*GPx↑,
*H2O2↓,
*ROS↓,
*lipid-P↓,
*HO-1↑, application of TQ to HaCaT (normal) cells promoted the expression of HO-1 in a concentration and time-dependent pattern
p‑Akt↓, TQ could induce ROS which provoked phosphorylation and activation of Akt and AMPK-α
AMPKα↑,
NK cell↑, TQ was outlined to enhance natural killer (NK) cells activity
selectivity↑, Many researchers have noticed that the growth inhibitory potential of TQ is particular to cancer cells
Dose↝, Moreover, TQ has a dual effect in which it can acts as both pro-oxidant and antioxidant in a dose-dependent manner; it acts as an antioxidant at low concentration whereas, at higher concentrations it possess pro-oxidant property
eff↑, Pro-oxidant property of TQ occurs in the presence of metal ions including copper and iron which induce conversion of TQ into semiquinone. This leads to generation of reactive oxygen species (ROS) causing DNA damage and induction of cellular apoptosis
GSH↓, TQ for one hour resulted in three-fold increase of ROS while reduced GSH level by 60%
eff↓, pre-treatment of cells with N-acetylcysteine, counteracted TQ-induced ROS production and alleviated growth inhibition
P53↑, TQ provokes apoptosis in MCF-7 cancer cells by up regulating the expression of P53 by time-dependent manner.
p‑STAT3↓, TQ inhibited the phosphorylation of STAT3
PI3K↑, via up regulation of PI3K and MPAK signalling pathway
MAPK↑,
GSK‐3β↑, TQ produced apoptosis in cancer cells and modulated Wnt signaling by activating GSK-3β, translocating β-catenin
ChemoSen↑, Co-administration of TQ and chemotherapeutic agents possess greater cytotoxic influence on cancer cells.
RadioS↑, Treatment of cells with both TQ and IR enhanced the antiproliferative power of TQ as observed by shifting the IC50 values for MCF7 and T47D cells from ∼104 and 37 μM to 72 and 18 μM, respectively.
BioAv↓, TQ cannot be used as the primary therapeutic agent because of its poor bioavailability [177,178] and lower efficacy
NRF2↑, TQ to HaCaT cells promoted the expression of HO-1 in a concentration and time-dependent pattern. This was achieved via increasing stabilization of Nrf2

2105-

TQ,

Thymoquinone Promotes Pancreatic Cancer Cell Death and Reduction of Tumor Size through Combined Inhibition of Histone Deacetylation and Induction of Histone Acetylation

in-vitro,

PC,

AsPC-1

10–50 μM

in-vitro,

PC,

MIA PaCa-2

in-vitro,

PC,

Hs766t

in-vivo,

NA,

mice

tumCV↓, Tq (10–50 μM) inhibited cell viability and proliferation and caused partial G2 cycle arrest in dose-dependent manner in both cell lines.
TumCP↓,
TumCCA↑, Cells accumulated in subG0/G1 phase, indicating apoptosis
Apoptosis↑,
P53↑, upregulation of p53 and downregulation of Bcl-2.
Bcl-2↓,
P21↑, Tq increased p21 mRNA expression 12-fold
ac‑H4↑, Tq also induced H4 acetylation
HDAC↓, downregulated HDACs activity, reducing expression of HDACs 1, 2, and 3 by 40–60%
HDAC1↓,
HDAC2↓,
HDAC3↓,
TumVol↓, Tq significantly reduced tumor size in 67% of established tumor xenografts

2104-

TQ,

The Potential Role of Nigella sativa Seed Oil as Epigenetic Therapy of Cancer

in-vitro,

BC,

MCF-7

in-vitro,

Cerv,

HeLa

TumCP↓, BSO significantly inhibited the proliferation of MCF-7, HeLa and Jurkat cells in a dose-dependent manner, and it induced apoptosis in these cell lines.
Apoptosis↑,
UHRF1↓, BSO-induced inhibitory effects were associated with a significant decrease in mRNA expression of UHRF1, DNMT1 and HDAC1
DNMT1↓,
HDAC1↓,
eff↝, A recent report showed that BSO content of TQ can vary from as low as 0.01 mg/g to 13.30 mg/g

2103-

TQ,

Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells

in-vitro,

PC,

Hs766t

25–75 µM

in-vitro,

PC,

MIA PaCa-2

MCP1↓, Tq dose- and time-dependently significantly reduced PDA cell synthesis of MCP-1, TNF-α, interleukin (IL)-1β and Cox-2.
TNF-α↓,
IL1β↓,
COX2↓,
NF-kB↓, Tq also inhibited the constitutive and TNF-α-mediated activation of NF-κB in PDA cells and reduced the transport of NF-κB from the cytosol to the nucleus.
HDAC↓, Tq also increased p21 WAF1 expression, inhibited histone deacetylase (HDAC) activity, and induced histone hyperacetylation
P21↑,

2102-

TQ,

A review on therapeutic potential of Nigella sativa: A miracle herb

Review,

Var,

angioG↓, TQ inhibits tumor angiogenesis and tumor growth through suppressing NF-κB and its regulated molecules.
NF-kB↓,
PPARγ↓, TQ was found to increase PPAR-γ activity and down-regulate the expression of the genes for Bcl-2, Bcl-xL and survivin in breast cancer cells.
Bcl-2↓,
Bcl-xL↓,
MUC4↓, TQ down regulated MUC4 expression through the proteasomal pathway and induced apoptosis in pancreatic cancer cells by the activation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase pathways
cJun↑,
p38↑,
P21↑, TQ also increased p21 WAF1 expression, inhibited HDAC activity, and induced histone hyperacetylation
HDAC↓,
radioP↑, N. sativa oil is a promising natural radioprotective agent against immunosuppressive and oxidative effects of ionizing radiation
hepatoP↑, Results suggested that N. sativa treatment protects the rat liver against hepatic ischemia reperfusion injury

2101-

TQ,

HDAC inhibition by Nigella sativa L. sprouts extract in hepatocellular carcinoma: an approach to study anti-cancer potential

Study,

HCC,

HDAC↓, bioactive compound of N. sativa, i.e. thymoquinone, also showed a good binding affinity with the HDAC protein (3MAX) with a stable interaction in an in silico study
eff↑, Extract of 5thday sprout N. sativa has been already testified to be more active towards HepG2 cells as compared to seed extract.
eff↑, The amounts of TQ and THY were 2.22 mg/mL and 3.92 mg/mL respectively in seed extracts whereas it was 4.88 mg/mL and 3.22 mg/mL respectively in 5d sprout extract
AntiCan↑, This study also showed first time 5d sprout of N. sativa inhibited the expression of HDAC and showed anti- cancer activity.

2100-

TQ,

Dual properties of Nigella Sative: Anti-oxidant and Pro-oxidant

Review,

NA,

ROS⇅, Pubmed data indicated that NS has both anti-oxidant and pro-oxidant properties in different cell types
*antiOx↑, NS acts as an anti-oxidant by scavenging ROS [4]. It can ameliorate ischemic reperfusion injury conditions and attenuated ROS in heart [5] intestine [6] and kidney [7]
*SOD↑, improved the activities of various enzymes like superoxide dismutase [SOD] and myeloperoxidase (MPO)
*MPO↑,
*neuroP↑, NS oil has been found to be neuroprotective against oxidative stress in epileptogenesis, pilocarpine-induced seizures [25] and opioid tolerance
*chemoP↑, Anticancer drugs leave toxic effect due to over-production of ROS. NS oil or TQ can potentially up-regulate anti-oxidant mechanisms caused by anticancer drug
*radioP↑, NS seed extracts can protect normal tissue from oxidative damage during radiotherapy of cancer patients [35,36]
NF-kB↓, TQ has been shown to exhibit down regulation of NF-κB expression in lung cancer cells
IAP1↓, Anti-apoptotic (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc) and angiogenic genes (matrix metalloproteinase-9 orMMP-9) and vascular endothelial growth factor (VEGF) were down-regulated
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
COX2↓,
MMP9↓,
VEGF↓,
ROS↑, TQ causes release of ROS in ABC cells which in turn inhibits NF-κB activity
P21↑, TQ up regulated the expression of p21 and down regulated the histone deacetylase (HDAC) activity and induced histone hyperacetylation causing induction of apoptosis and inhibition of proliferation in pancreatic cancer cell
HDAC↓,
GSH↓, TQ was found to decrease glutathione (GSH) levels in prostate cancer cells resulting in up-regulated expression of GADD45 alpha (growth arrest and DNA damage inducible gene) and AIF
GADD45A↑,
AIF↑,
STAT3↓, TQ suppressed the STAT 3; the signal transducer and activator of transcription which is involved in the abnormal transformation of a number of human malignancies [53].

2099-

TQ,

Cisplatin,

Thymoquinone and cisplatin as a therapeutic combination in lung cancer: In vitro and in vivo

in-vitro,

Lung,

H460

in-vitro,

Lung,

H146

in-vivo,

NA,

mice

ChemoSen↑, TQ and CDDP appear to be an active therapeutic combination in lung cancer.
TumCP↓, TQ was able to inhibit cell proliferation, reduce cell viability and induce apoptosis.
tumCV↓,
Apoptosis↑,
NF-kB↓, suppression of NF-κB by TQ

2098-

TQ,

Anticancer activity of Nigella sativa (black seed) and its relationship with the thermal processing and quinone composition of the seed

in-vitro,

Colon,

MC38

in-vitro,

lymphoma,

L428

NF-kB↓, effect of the different methods of thermal processing on the ability of the obtained NS oil to inhibit the nuclear factor kappa B (NF-κB) pathway was then investigated in Hodgkin’s lymphoma (L428) cells.
eff↑, heating the NS seeds to 50°C, 100°C, or 150°C produced oil with a strong ability to inhibit tumor cell growth;
eff↓, no heating or heating to 25°C had a mild antiproliferative effect; and heating to 200°C or 250°C had no effect.

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 126

Results for Effect on Cancer/Diseased Cells:
5LO↓,2, AIF↑,1, Akt↓,9, Akt↑,2, p‑Akt↓,6, ALAT↓,2, AMPK↑,2, AMPKα↑,1, angioG↓,10, angioG↑,1, AntiCan↑,6, antiOx↑,3, AP-1↓,1, Apoptosis↓,3, Apoptosis↑,28, AR↓,1, ARE/EpRE↑,1, AST↓,1, ATF4↑,1, ATF6↑,1, ATG7↑,1, ATP↓,1, i-ATP↓,1, B2M↓,1, BAX↓,1, BAX↑,13, Bax:Bcl2↑,7, Bcl-2↓,21, Bcl-2↑,1, Bcl-xL↓,12, Beclin-1↑,1, BID↓,1, BioAv↓,5, BioAv↑,4, BioAv↝,3, CAIX↓,1, cardioP↑,1, Casp↑,7, Casp1↓,1, Casp3?,1, Casp3↑,16, cl‑Casp3↑,3, Casp7?,1, Casp7↑,5, cl‑Casp7↑,1, Casp8↑,5, cl‑Casp8↑,1, Casp9?,1, Casp9↓,1, Casp9↑,11, cl‑Casp9↑,1, Catalase↑,1, CD34↓,1, CDC2↓,1, cDC2↓,1, CDC25↓,1, CDK2↓,2, CDK4↓,3, CDK6↓,1, chemoP↑,8, ChemoSen↓,1, ChemoSen↑,13, CHOP↑,1, cJun↑,2, cMET↓,1, cMyc↓,7, COX2↓,13, creat↓,1, cSrc↓,1, CXCL1↓,1, CXCR4↓,3, cycA1↓,3, CycB↑,1, cycD1↓,17, CycD3↑,1, cycE↓,2, CYP1B1↑,2, Cyt‑c↑,9, DLC1↑,3, DNAdam↓,1, DNAdam↑,4, DNMT1↓,7, DNMT3A↓,1, DNMTs↓,1, Dose↝,3, DR4↑,1, DR5↑,3, E-cadherin↓,1, E-cadherin↑,5, E2Fs↓,1, eff↓,10, eff↑,21, eff↝,4, EGFR↓,1, eIF2α↓,1, p‑eIF2α↑,1, EMT↓,8, EP2↓,1, EP4↓,1, ER Stress↑,2, ERK↓,5, ERK↑,1, EZH2↓,1, FADD↑,1, FAK↓,1, Fas↑,1, FOXO↑,2, G9a↓,2, GADD45A↑,2, GCLM↑,1, Gli1↓,1, GlucoseCon↓,1, GLUT1↓,1, Glycolysis↓,2, GPx1⇅,1, GPx4↓,1, GRP78/BiP↑,2, GSH↓,6, GSH↑,1, GSH/GSSG↓,1, GSK‐3β↓,2, GSK‐3β↑,2, p‑GSK‐3β↓,2, GSSG↑,2, H2O2↓,1, H4↑,1, ac‑H4↑,1, HDAC↓,13, HDAC1↓,7, HDAC2↓,2, HDAC3↓,2, HDAC4↓,2, hepatoP↑,9, HH↓,1, Hif1a↓,3, HK2↓,1, HO-1↑,2, HSP70/HSPA5↓,1, HSP70/HSPA5↑,2, hTERT↓,2, IAP1↓,5, IAP2↓,4, IAP2↑,1, IL1↓,1, IL10↓,1, IL12↓,1, IL18↓,1, IL1β↓,2, IL2↑,1, IL6↓,1, IL8↓,1, Inflam↓,4, iNOS↓,2, IRE1↑,1, ITGA5↓,1, IκB↓,1, JAK2↓,5, p‑JAK2↓,1, JNK↓,1, JNK↑,3, Jun↓,1, Ki-67↓,4, lactateProd↓,1, e-lactateProd↓,1, LC3II↑,1, LDH↑,1, LDHA↓,1, lipid-P↑,1, MAPK↓,1, MAPK↑,3, p‑MAPK↑,2, Maspin↑,1, Mcl-1↓,2, MCP1↓,2, MDA↑,1, MDM2↓,1, MDR1↓,1, MEK↓,1, MET↓,1, miR-29b↑,1, miR-34a↑,1, MMP↓,9, MMP2↓,4, MMP7↓,2, MMP9↓,9, MMPs↓,2, mTOR↓,6, p‑mTOR↓,1, MUC4↓,5, Myc↓,1, MyD88↓,1, N-cadherin↓,4, NADPH↓,1, neuroP↑,3, NF-kB↓,23, NF-kB↑,1, p‑NF-kB↑,1, NK cell↑,1, NLRP3↓,2, NO↑,1, NOTCH↓,3, NQO1↑,1, NRF2↓,1, NRF2↑,5, p16↑,2, P21↑,16, p27↑,4, p38↑,6, p‑p38↑,2, P53↑,17, P53⇅,1, p65↓,2, p‑p65↓,1, P70S6K↓,1, PARP↓,1, cl‑PARP↑,13, PD-L1↓,3, PDK1↓,1, PERK↑,1, PGE1↓,1, PGE2↓,1, PI3K↓,9, PI3K↑,1, p‑PI3K↓,2, PI3k/Akt/mTOR↓,1, PKM2↓,3, PPARγ↓,2, PPARγ↑,3, PTEN↑,6, Rac1↓,2, radioP↑,3, RadioS↑,5, Raf↓,1, RAS↓,1, RenoP↑,3, ROS↓,3, ROS↑,37, ROS⇅,5, selectivity↑,15, Shh↓,1, SIRT1↓,1, Slug↓,2, SMAD2↓,1, SMAD3↓,1, Snail↓,1, SOD↑,1, Sp1/3/4↓,2, c-Src↓,1, STAT3↓,10, p‑STAT3↓,5, survivin↓,17, Telomerase↓,1, TET2↑,2, TGF-β↓,2, TGF-β↑,1, TLR4↓,1, TNF-α↓,6, TRAIL↑,2, TRIF↓,1, TumCCA↓,1, TumCCA↑,22, TumCD↑,1, TumCG↓,4, TumCI↓,7, TumCMig↓,7, TumCP↓,22, tumCV↓,11, tumCV↑,1, TumMeta↓,9, TumVol↓,4, Twist↓,7, UHRF1↓,4, uPAR↓,1, VEGF↓,10, VEGFR2↓,2, Vim↓,3, Warburg↓,2, Wnt↓,1, XIAP↓,11, Zeb1↓,3, α-tubulin↓,1, β-catenin/ZEB1↓,4, p‑γH2AX↑,1,
Total Targets: 283

Results for Effect on Normal Cells:
Ach↑,3, AChE↓,7, AChE↝,1, p‑Akt↓,2, p‑Akt↑,1, e-Akt↑,1, ALAT↓,4, ALP↓,1, AMPKα↑,1, angioG↑,2, AntiAge↑,1, AntiCan↑,2, antiOx↓,2, antiOx↑,19, Apoptosis↓,2, ASC?,1, AST↓,4, mt-ATPase↑,1, Aβ↓,7, Aβ↑,1, BACE↓,1, Bacteria↓,1, BAX↓,3, Bax:Bcl2↓,1, BBB↑,2, Bcl-2↑,1, BioAv↓,3, BioAv↑,4, BioAv↝,2, BUN↓,1, cardioP↑,8, Casp1?,1, Casp1↓,1, Casp3↓,6, cl‑Casp3↓,1, proCasp3↓,1, Casp7↓,1, Catalase↑,15, ChAT↑,1, chemoP↑,2, p‑cJun↓,1, cMyc↓,1, cognitive↑,10, COX2↓,10, creat↓,1, CRP↓,3, CXCc↓,1, cycD1↓,1, Diff↑,1, eff↓,1, eff↑,6, eNOS↑,1, e-ERK↑,1, FTH1↑,1, GABA↑,1, GCLC↑,1, GFR↑,1, GPx↑,8, GPx4↑,1, GR↑,1, GSH↑,23, GSH/GSSG↑,1, GSR↑,2, GSSG↓,2, GSTA1↓,1, GSTA1↑,4, GSTs↑,3, H2O2↓,3, Half-Life↝,2, hepatoP↑,10, Hif1a↑,2, HO-1↓,1, HO-1↑,11, IFN-γ↓,2, IFN-γ↑,1, IL10↑,3, IL12↓,3, IL18↓,1, IL1β↓,15, IL1β↑,1, IL6↓,7, Inflam↓,20, Inflam↑,1, iNOS↓,3, iNOS↑,1, IP-10/CXCL-10↓,1, IRF3↓,4, IκB↑,1, JNK↑,1, Keap1↓,1, LDH↓,2, LDL↓,1, lipid-P↓,13, LOX1↓,1, MAPK↓,1, MAPK↑,1, MCP1↓,2, MDA↓,13, memory↑,9, MMP↑,5, MMP13↓,2, MMP7↓,1, MMP9↓,1, MMP9↑,1, MMPs↓,1, motorD↑,2, MPO↓,1, MPO↑,1, MRP↓,1, p‑mTOR↓,1, MyD88↓,3, NAD↑,1, NADPH↑,1, neuroG↑,1, neuroP↑,16, NF-kB↓,16, NLRP3↓,2, NO↓,3, NO↑,1, NOX4↓,1, NQO1↑,3, NRF2↓,1, NRF2↑,14, OS↑,2, other↝,1, p38↓,1, p‑p38↓,1, PGE2↓,4, PI3K↑,1, PPARγ↑,1, Prx↑,1, Pyro?,1, radioP↑,3, RenoP↑,10, ROS↓,32, ROS↑,1, SIRT1↑,2, SOD↓,1, SOD↑,22, SOD1↑,3, TAC↑,3, p‑tau↓,3, TGF-β↓,4, Thiols↑,2, TLR1↓,1, TLR2↓,4, TLR4↓,4, TNF-α↓,14, toxicity↓,3, toxicity∅,1, TRIF↓,2, TrkB↑,1, TumCI↓,1, TumCI∅,1, TumCMig∅,1, TumCP↓,1, tumCV∅,1, TXNIP↓,1, VEGF↓,1, VEGF↑,2, VitC↑,1, VitE↑,1, Weight∅,1,
Total Targets: 163

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

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