Database Query Results : Thymoquinone, , NF-kB

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↓">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↓, 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

Rank	Pathway / Target Axis	Direction	Label	Primary Effect	Notes / Cancer Relevance	Ref
1	Reactive oxygen species (ROS)	↑ ROS	Driver	Upstream cytotoxic trigger	Primary studies show TQ rapidly increases ROS; antioxidant/ROS modulation attenuates downstream effects, supporting ROS as an initiating mechanism in multiple cancer contexts	(ref)
2	Glutathione (GSH) redox buffering	↓ GSH	Driver	Redox-collapse amplification	Same prostate cancer study reports early GSH depletion alongside ROS rise; together these form a redox “one-two punch” that helps explain selective stress in tumor cells	(ref)
3	Mitochondrial integrity (ΔΨm)	↓ ΔΨm	Driver	Mitochondrial dysfunction (MOMP axis)	Primary leukemia/cancer study reports disruption of mitochondrial membrane potential after TQ exposure (mitochondrial events central to TQ-mediated death)	(ref)
4	Intrinsic apoptosis (caspase-9 → caspase-3; PARP)	↑ caspases / ↑ apoptosis	Driver	Execution-phase cell death	Same primary paper reports activation of caspases (8/9/3) with mitochondrial involvement—core evidence for apoptosis as the major outcome pathway	(ref)
5	NF-κB signaling	↓ NF-κB activity	Secondary	Reduced pro-survival / inflammatory transcription	Colon cancer work: TQ induces cell death and chemosensitizes cells by inhibiting NF-κB signaling (explicit pathway-direction support)	(ref)
6	STAT3 signaling	↓ p-STAT3 / ↓ STAT3 activation	Secondary	Reduced survival/proliferation signaling	Gastric cancer study explicitly reports TQ suppresses constitutive STAT3 activation and related signaling readouts	(ref)
7	NRF2 antioxidant-response axis (NRF2/HO-1 program)	↑ NRF2 pathway (often as stress-response)	Adaptive	Cellular antioxidant counter-response	In TNBC context, a primary study reports TQ upregulates NRF2 (and evaluates downstream immune/checkpoint consequences), consistent with NRF2 acting as an adaptive response to redox stress	(ref)
8	HIF-1α hypoxia signaling	↓ HIF-1α protein / ↓ HIF-1α program	Adaptive	Loss of hypoxia survival signaling	Renal cancer hypoxia paper identifies TQ as suppressing HIF-1α and links this to selective killing under hypoxia	(ref)
9	Glycolysis / Warburg output (hypoxia-linked)	↓ glycolysis (↓ HIF-1α–mediated glycolytic genes; ↓ glycolytic metabolism)	Phenotypic	Metabolic suppression	In hypoxic renal cancer, TQ suppresses HIF-1α–mediated glycolysis; in CRC, TQ inhibits glycolytic metabolism alongside tumor growth limitation	(ref) \| (ref)

NF-kB, Nuclear factor kappa B: Click to Expand ⟱

Source: HalifaxProj(inhibit)

Type:

NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.

Scientific Papers found: Click to Expand⟱

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↑,

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)

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

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↓,

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.

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↓,

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/CCND1↓,
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↓,

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↑,

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

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/CCND1↓,
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.

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

3573-

TQ,

Chronic diseases, inflammation, and spices: how are they linked?

Review,

Var,

NF-kB↓, Bladder cancer ↓NF-κB, ↓XIAP
XIAP↓,
PI3K↓, Cholangiocarcinoma ↓PI3K/Akt, ↓NF-κB
Akt↓,
STAT3↓, Gastric cancer ↓STAT3, ↓JAK2, ↓c-Src
JAK2↓,
cSrc↓,
PCNA↓, Lung cancer ↓PCNA, ↓CD1, ↓MMP-2, ↓ERK1/2
MMP2↓,
ERK↓,
Ki-67↓, Multiple myeloma ↓Ki-67, ↓VEGF, ↓Bcl-2, ↓p65
Bcl-2↓,
VEGF↓,
p65↓,
COX2↓, Myeloid leukemia ↓NF-κB, ↓CD1, ↓COX-2, ↓MMP-9
MMP9↓,

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

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

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)

4565-

TQ,

Thymoquinone in the clinical treatment of cancer: Fact or fiction?

Review,

BC,

Dose↝, high performance liquid chromatography of the seeds oil of N. sativa revealed that TQ may attain up to 27.8% of the volatile oil (w/w) composition.
TumCCA↑, It was shown to induce G1/S cell cycle arrest by up-regulating p21WAF1/Cip1[19] or p27Kip1[20] and down-regulating cyclin D1[21] and was reported to control invasion and metastasis of cancer.
P21↑,
cycD1/CCND1↓,
TumCI↑,
TumMeta↓,
Bcl-2↓, down-regulate PPAR-γ related genes, including Bcl-2, Bcl-xL and survivin at both mRNA and protein expression levels in MCF-7 cells.
Bcl-xL↓,
survivin↓,
PTEN↑, TQ induces apoptosis in doxorubicin-resistant breast cancer cells through the up-regulation of phosphatase and tensin homolog (PTEN) at the transcription level.
Akt↓, The up-regulated PTEN, in turn, inhibits the phosphatidylinositol-3 kinase/Akt pathway and induces p53 and p21 protein expression
P53↑,
NF-kB↓, Inhibition of NF-κB by TQ increases apoptosis in hyperplastic stages of tumor development and decreases proliferation at least in part by reducing CyclinD1 expression, which inhibits mammary tumor progression.
cardioP↑, TQ has an antioxidant protective effect against the doxorubicin-induced cardiotoxicity
Dose↝, Patients with breast cancer were under treatment for 2 weeks with 400 mg/day. The authors reported neither toxicity nor therapeutic response.

5024-

TQ,

Thymoquinone: A Tie-Breaker in SARS-CoV2-Infected Cancer Patients?

Review,

Covid,

*NRF2↑, TQ on Nrf2; it activates Nrf2 by phosphorylation,
*NF-kB↓, results in the reduction of NF-kB, cytokine production, inflammation, oxidative damage and an increase in detoxifying cytoprotective genes and enzymes such as the HO-1 enzyme.
*Inflam↓,
*ROS↓,
*HO-1↑,
antiOx↑, TQ happens to demonstrate potent antioxidant properties, where it significantly attenuates glutathione (GSH) depletion and increases the activity of the glutathione-S-transferase (GST) enzyme.
GSH↑,
GSTs↑,
GSR↑, TQ induces the expression of several detoxifying enzymes, including glutathione reductase, superoxide dismutase 1 (SOD1), catalase, and glutathione peroxidase 2 (GPX)
SOD1↑,
Catalase↑,
GPx↑,
p62↓, TQ significantly decreased P62 and increased expression of beclin1 in CLP mice, thus decreasing sepsis-induced cardiac damage.
Beclin-1↑,
Sepsis↓,
cardioP↑,
hepatoP↑, TQ shows several promising hepatoprotective effects
neuroP↑, TQ shows several neuroprotective effects, as summarized in Table 4

5222-

TQ,

Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB

in-vitro,

CRC,

COLO205

40 µM TQ

in-vitro,

CRC,

HCT116

tumCV↓, TQ significantly decreased cell viability in COLO205 and HCT116 cells in a dose-dependent manner.
ChemoSen↑, TQ treatment additionally sensitized COLO205 and HCT116 cells to cisplatin therapy in a concentration-dependent manner.
p‑p65↓, TQ treatment significantly decreased the level of phosphorylated p65 in the nucleus, which indicated the inhibition of NF-κB activation by TQ treatment.
NF-kB↓,
VEGF↓, TQ also decreased the expression levels of VEGF, c-Myc and Bcl-2.
cMyc↓,
Bcl-2↓,
ROS↑, TQ-induced apoptosis has been indicated to be mediated by reactive oxygen species generation (29,33,37)

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/CCND1↓,
*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

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%

3429-

TQ,

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

in-vitro,

AML,

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/CCND1↓,
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/CCND1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
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

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↓,

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
*chemoPv↑, 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/CCND1↓, 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
chemoPv↑, 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.

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.

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↓,

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

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/TERT↓,
cycD1/CCND1↓,
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

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.

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

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].

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

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

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
chemoPv↑, 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

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]

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↑,

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. (ai:once TQ reduces oxidative damage, the demand for high Nrf2 activity drops)
*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).

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

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

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↑,

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/CCND1↓,
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

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 43

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

Sepsis↓, 1,
Total Targets: 209

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 9, Catalase↑, 6, GCLC↑, 1, GPx↑, 4, GSH↑, 7, GSR↑, 2, GSTA1↑, 3, GSTs↑, 3, H2O2↓, 1, HO-1↓, 1, HO-1↑, 5, lipid-P↓, 6, MDA↓, 5, MPO↓, 1, MPO↑, 1, NQO1↑, 1, NRF2↓, 1, NRF2↑, 6, ROS↓, 16, SOD↑, 7, SOD1↑, 1, TAC↑, 2, Thiols↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↑, 3,

Core Metabolism/Glycolysis ⓘ

BUN↓, 1, cMyc↓, 1, LDH↓, 2, NAD↑, 1, NADPH↑, 1, PPARγ↑, 1, SIRT1↑, 2,

Cell Death ⓘ

p‑Akt↓, 1, p‑Akt↑, 1, Apoptosis↓, 2, BAX↓, 2, Casp1↓, 1, Casp3↓, 4, iNOS↓, 2, iNOS↑, 1, JNK↑, 1, MAPK↓, 1, MAPK↑, 1, p38↓, 1, p‑p38↓, 1, Pyro?, 1,

Transcription & Epigenetics ⓘ

p‑cJun↓, 1,

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1,

Migration ⓘ

mt-ATPase↑, 1, MMP13↓, 2, MMP7↓, 1, MMP9↓, 1, MMP9↑, 1, TGF-β↓, 3, TumCI↓, 1, TumCP↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 1, eNOS↑, 1, Hif1a↑, 1, LOX1↓, 1, NO↓, 1, VEGF↓, 1, VEGF↑, 1,

Barriers & Transport ⓘ

BBB↑, 1, MRP↓, 1,

Immune & Inflammatory Signaling ⓘ

ASC?, 1, COX2↓, 7, CRP↓, 3, IFN-γ↓, 1, IL10↑, 2, IL12↓, 2, IL18↓, 1, IL1β↓, 11, IL6↓, 5, Inflam↓, 13, IP-10/CXCL-10↓, 1, IκB↑, 1, MCP1↓, 1, MyD88↓, 3, NF-kB↓, 17, PGE2↓, 3, TLR2↓, 4, TLR4↓, 4, TNF-α↓, 8, TRIF↓, 2,

Synaptic & Neurotransmission ⓘ

AChE↓, 2, GABA↑, 1, p‑tau↓, 2,

Protein Aggregation ⓘ

Aβ↓, 5, BACE↓, 1, NLRP3↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, BioAv↑, 1, BioAv↝, 2, eff↑, 2, Half-Life↝, 2,

Clinical Biomarkers ⓘ

creat↓, 1, CRP↓, 3, IL6↓, 5, LDH↓, 2,

Functional Outcomes ⓘ

AntiCan↑, 1, cardioP↑, 2, chemoP↑, 1, chemoPv↑, 1, cognitive↑, 4, GFR↑, 1, hepatoP↑, 3, memory↑, 4, motorD↑, 1, neuroP↑, 5, OS↑, 1, radioP↑, 4, RenoP↑, 5, toxicity↓, 1, Weight∅, 1,

Infection & Microbiome ⓘ

IRF3↓, 4,
Total Targets: 116

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B

43 Thymoquinone
2 Cisplatin
1 5-fluorouracil
1 Curcumin

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:214  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : Thymoquinone, , NF-kB

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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