condition found 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↓">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↓, 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


ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK: regulates energy metabolism and can increase ROS levels when activated.
• mTOR: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Melavonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day
-Dipyridamole typically 200mg 2x/day
-Lycopene typically 100mg/day range

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

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

3407- TQ,    Thymoquinone and its pharmacological perspective: A review
- Review, NA, 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)

3401- TQ,    Molecular mechanisms and signaling pathways of black cumin (Nigella sativa) and its active constituent, thymoquinone: a review
- Review, Var, NA
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↑,

3403- TQ,    A multiple endpoint approach reveals potential in vitro anticancer properties of thymoquinone in human renal carcinoma cells
- in-vitro, RCC, 786-O
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, NA - Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*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, NA
*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↓,

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, NA
*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

3409- TQ,    Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives
- in-vivo, Nor, NA
*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, NA
*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, NA
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, NA
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,    ROS%20was%20induced,TQ%20in%20SCLC%20cell%20lines">The anti-neoplastic impact of thymoquinone from Nigella sativa on small cell lung cancer: In vitro and in vivo investigations
- in-vitro, Lung, H446
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, NA
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.

2136- TQ,    Nigella sativa and thymoquinone suppress cyclooxygenase-2 and oxidative stress in pancreatic tissue of streptozotocin-induced diabetic rats
- in-vivo, Nor, NA
*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
*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, NA
*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.

2131- TQ,    Therapeutic impact of thymoquninone to alleviate ischemic brain injury via Nrf2/HO-1 pathway
- in-vitro, Stroke, NA - in-vivo, Nor, NA
*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, NA
*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
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, NA - Review, Park, NA
*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).

3571- TQ,    The Role of Thymoquinone in Inflammatory Response in Chronic Diseases
- Review, Var, NA - Review, Stroke, NA
*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)

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, NA
*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

3559- TQ,    Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer’s disease
- Review, AD, NA - Review, Var, NA
*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

3554- TQ,    Neuroprotective efficacy of thymoquinone against amyloid beta-induced neurotoxicity in human induced pluripotent stem cell-derived cholinergic neurons
- in-vitro, AD, NA
*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.

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

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, NA
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, NA
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↓,

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, NA
*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↓,

3418- TQ,    Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome
- in-vitro, Melanoma, A375 - in-vivo, NA, NA
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.

1936- TQ,    Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line
- in-vitro, Ovarian, CaOV3 - 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

2095- TQ,    Review on the Potential Therapeutic Roles of Nigella sativa in the Treatment of Patients with Cancer: Involvement of Apoptosis
- Review, Var, NA
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, NA
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

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, NA
*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.

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, NA
*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↓,

2084- TQ,    Thymoquinone, as an anticancer molecule: from basic research to clinical investigation
- Review, Var, NA
*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.

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
*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↑,

1935- TQ,    Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis
- Review, OS, NA
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 - in-vitro, Pca, C4-2B
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, NA
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, NA
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, NA
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, NA
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 - in-vitro, Bladder, T24
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↑,

2112- TQ,    Crude flavonoid extract of the medicinal herb Nigella sativa inhibits proliferation and induces apoptosis in breastcancer cells
- in-vitro, BC, MCF-7
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, NA
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]

2124- TQ,    Thymoquinone: an emerging natural drug with a wide range of medical applications
- Review, Var, NA
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
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, NA
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,    ROS">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,    ROS-mediated_suppression_of_STAT3">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, NA
*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, NA
*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, NA
*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, NA
*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↓,

2113- TQ,    Potential role of Nigella sativa (NS) in abating oxidative stress-induced toxicity in rats: a possible protection mechanism
- in-vivo, Nor, NA
*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↓,

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 - in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, Nor, HEK293
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
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, NA
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

2106- TQ,    Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy
- Review, Var, NA
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

2100- TQ,    Dual properties of Nigella Sative: Anti-oxidant and Pro-oxidant
- Review, NA, 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].


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 67

Results for Effect on Cancer/Diseased Cells:
5LO↓,1,   AIF↑,1,   Akt↓,8,   Akt↑,1,   p‑Akt↓,5,   ALAT↓,2,   AMPK↑,2,   AMPKα↑,1,   angioG↓,7,   angioG↑,1,   AntiCan↑,4,   antiOx↑,3,   AP-1↓,1,   Apoptosis↓,2,   Apoptosis↑,18,   AR↓,1,   ARE/EpRE↑,1,   AST↓,1,   ATG7↑,1,   BAX↓,1,   BAX↑,10,   Bax:Bcl2↑,5,   Bcl-2↓,15,   Bcl-2↑,1,   Bcl-xL↓,8,   Beclin-1↑,1,   BID↓,1,   BioAv↓,5,   BioAv↑,3,   BioAv↝,1,   cardioP↑,1,   Casp↑,6,   Casp1↓,1,   Casp3↑,12,   cl‑Casp3↑,1,   Casp7↑,5,   Casp8↑,3,   Casp9↑,10,   cl‑Casp9↑,1,   Catalase↑,1,   CD34↓,1,   CDC2↓,1,   cDC2↓,1,   CDC25↓,1,   CDK2↓,1,   CDK4↓,2,   CDK6↓,1,   chemoP↑,6,   ChemoSen↓,1,   ChemoSen↑,10,   cMET↓,1,   cMyc↓,6,   COX2↓,9,   creat↓,1,   cSrc↓,1,   CXCL1↓,1,   CXCR4↓,3,   cycA1↓,2,   CycB↑,1,   cycD1↓,13,   CycD3↑,1,   cycE↓,1,   CYP1B1↑,1,   Cyt‑c↑,6,   DLC1↑,1,   DNAdam↓,1,   DNAdam↑,4,   DNMT1↓,4,   Dose↝,2,   DR4↑,1,   DR5↑,3,   E-cadherin↓,1,   E-cadherin↑,3,   E2Fs↓,1,   eff↓,9,   eff↑,15,   eff↝,1,   EGFR↓,1,   eIF2α↓,1,   EMT↓,6,   ERK↓,5,   ERK↑,1,   EZH2↓,1,   FADD↑,1,   FAK↓,1,   Fas↑,1,   FOXO↑,1,   G9a↓,1,   GADD45A↑,2,   GCLM↑,1,   GPx1⇅,1,   GPx4↓,1,   GSH↓,6,   GSH↑,1,   GSH/GSSG↓,1,   GSK‐3β↓,2,   GSK‐3β↑,2,   p‑GSK‐3β↓,1,   GSSG↑,2,   H2O2↓,1,   H4↑,1,   HDAC↓,6,   HDAC1↓,4,   HDAC2↓,1,   HDAC3↓,1,   HDAC4↓,1,   hepatoP↑,8,   HO-1↑,1,   HSP70/HSPA5↑,2,   hTERT↓,1,   IAP1↓,4,   IAP2↓,3,   IAP2↑,1,   IL1↓,1,   IL10↓,1,   IL12↓,1,   IL18↓,1,   IL1β↓,1,   IL2↑,1,   IL6↓,1,   IL8↓,1,   Inflam↓,4,   iNOS↓,1,   ITGA5↓,1,   IκB↓,1,   JAK2↓,4,   p‑JAK2↓,1,   JNK↓,1,   JNK↑,3,   Jun↓,1,   Ki-67↓,4,   LC3II↑,1,   lipid-P↑,1,   MAPK↓,1,   MAPK↑,3,   p‑MAPK↑,2,   Mcl-1↓,2,   MCP1↓,1,   MDA↑,1,   MDM2↓,1,   MDR1↓,1,   MEK↓,1,   MET↓,1,   miR-34a↑,1,   MMP↓,8,   MMP2↓,3,   MMP7↓,2,   MMP9↓,8,   MMPs↓,2,   mTOR↓,6,   p‑mTOR↓,1,   MUC4↓,3,   Myc↓,1,   N-cadherin↓,3,   neuroP↑,3,   NF-kB↓,15,   p‑NF-kB↑,1,   NK cell↑,1,   NLRP3↓,2,   NO↑,1,   NOTCH↓,3,   NQO1↑,1,   NRF2↓,1,   NRF2↑,3,   p16↑,2,   P21↑,11,   p27↑,4,   p38↑,4,   p‑p38↑,2,   P53↑,15,   p65↓,2,   p‑p65↓,1,   P70S6K↓,1,   PARP↓,1,   cl‑PARP↑,10,   PD-L1↓,2,   PI3K↓,8,   PI3K↑,1,   p‑PI3K↓,1,   PKM2↓,1,   PPARγ↓,1,   PPARγ↑,2,   PTEN↑,6,   Rac1↓,1,   RadioS↑,4,   Raf↓,1,   RAS↓,1,   RenoP↑,3,   ROS↓,3,   ROS↑,37,   ROS⇅,5,   selectivity↑,11,   SIRT1↓,1,   Slug↓,1,   Snail↓,1,   SOD↑,1,   STAT3↓,10,   p‑STAT3↓,4,   survivin↓,14,   Telomerase↓,1,   TET2↑,1,   TGF-β↓,1,   TGF-β↑,1,   TNF-α↓,3,   TRAIL↑,2,   TumCCA↓,1,   TumCCA↑,18,   TumCG↓,2,   TumCI↓,6,   TumCMig↓,5,   TumCP↓,11,   tumCV↓,7,   TumMeta↓,7,   TumVol↓,1,   Twist↓,7,   UHRF1↓,2,   VEGF↓,8,   VEGFR2↓,2,   Vim↓,2,   Warburg↓,1,   Wnt↓,1,   XIAP↓,9,   Zeb1↓,3,   α-tubulin↓,1,   β-catenin/ZEB1↓,3,   p‑γH2AX↑,1,  
Total Targets: 226

Results for Effect on Normal Cells:
Ach↑,1,   AChE↓,3,   AChE↝,1,   e-Akt↑,1,   ALAT↓,2,   AMPKα↑,1,   angioG↑,1,   AntiCan↑,1,   antiOx↓,2,   antiOx↑,11,   Apoptosis↓,2,   ASC?,1,   AST↓,2,   Aβ↓,4,   BACE↓,1,   BAX↓,1,   BioAv↓,3,   BioAv↑,3,   BioAv↝,2,   BUN↓,1,   cardioP↑,5,   Casp1↓,1,   Casp3↓,3,   Casp7↓,1,   Catalase↑,12,   chemoP↑,2,   cMyc↓,1,   cognitive↑,4,   COX2↓,9,   CRP↓,3,   CXCc↓,1,   cycD1↓,1,   eff↓,1,   eff↑,4,   eNOS↑,1,   e-ERK↑,1,   FTH1↑,1,   GABA↑,1,   GPx↑,7,   GPx4↑,1,   GR↑,1,   GSH↑,14,   GSH/GSSG↑,1,   GSR↑,2,   GSSG↓,2,   GSTA1↓,1,   GSTA1↑,1,   GSTs↑,3,   H2O2↓,3,   Half-Life↝,2,   hepatoP↑,5,   HO-1↑,9,   IFN-γ↓,2,   IL10↑,2,   IL12↓,3,   IL18↓,1,   IL1β↓,10,   IL6↓,5,   Inflam↓,10,   Inflam↑,1,   iNOS↓,3,   iNOS↑,1,   IP-10/CXCL-10↓,1,   IRF3↓,2,   JNK↑,1,   LDH↓,2,   lipid-P↓,9,   LOX1↓,1,   MAPK↓,1,   MAPK↑,1,   MCP1↓,2,   MDA↓,8,   memory↑,5,   MMP↑,5,   MMP13↓,2,   MMP9↓,1,   MMP9↑,1,   MMPs↓,1,   MPO↓,1,   MPO↑,1,   p‑mTOR↓,1,   MyD88↓,2,   NAD↑,1,   neuroP↑,10,   NF-kB↓,10,   NLRP3↓,1,   NO↓,1,   NO↑,1,   NOX4↓,1,   NQO1↑,2,   NRF2↑,10,   OS↑,2,   p38↓,1,   PGE2↓,4,   PPARγ↑,1,   Prx↑,1,   Pyro?,1,   radioP↑,2,   RenoP↑,5,   ROS↓,32,   ROS↑,1,   SIRT1↑,2,   SOD↓,1,   SOD↑,17,   SOD1↑,2,   TAC↑,2,   p‑tau↓,2,   TGF-β↓,3,   Thiols↑,2,   TLR1↓,1,   TLR2↓,2,   TLR4↓,2,   TNF-α↓,6,   TRIF↓,1,   TumCI↓,1,   TumCP↓,1,   tumCV∅,1,   TXNIP↓,1,   VEGF↓,1,   VEGF↑,1,   VitC↑,1,   VitE↑,1,  
Total Targets: 122

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
67 Thymoquinone
3 doxorubicin
1 Juglone
1 Plumbagin
1 5-fluorouracil
1 Radiotherapy/Radiation
1 Cisplatin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:275  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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