| Source: TCGA |
| Type: Antiapoptotic |
| Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response. -One way to estimate Nrf2 induction is through the expression of NQO1. NQO1, the most potent inducer: SFN 0.2 μM, quercetin (2.5 μM), curcumin (2.7 μM), Silymarin (3.6 μM), tamoxifen (5.9 μM), genistein (6.2 μM ), beta-carotene (7.2μM), lutein (17 μM), resveratrol (21 μM), indol-3-carbinol (50 μM), chlorophyll (250 μM), alpha-cryptoxanthin (1.8 mM), and zeaxanthin (2.2 mM) 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. 3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress -In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. -Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic. -Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer - "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1. Nrf2 Inhibitors and Activators Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api - potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue. – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. – While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS). -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent . -Oridonin: -Wogonin: although its effects might be cell‑ and dose‑specific. - Withaferin A |
| 3310- | SIL, | Silymarin attenuates paraquat-induced lung injury via Nrf2-mediated pathway in vivo and in vitro |
| - | in-vitro, | Lung, | A549 |
| 3311- | SIL, | Silymarin protects against acrylamide-induced neurotoxicity via Nrf2 signalling in PC12 cells |
| - | in-vitro, | Nor, | PC12 |
| 2201- | SK, | Shikonin promotes ferroptosis in HaCaT cells through Nrf2 and alleviates imiquimod-induced psoriasis in mice |
| - | in-vitro, | PSA, | HaCaT | - | in-vivo, | NA, | NA |
| 2198- | SK, | Shikonin suppresses proliferation of osteosarcoma cells by inducing ferroptosis through promoting Nrf2 ubiquitination and inhibiting the xCT/GPX4 regulatory axis |
| - | in-vitro, | OS, | MG63 | - | in-vitro, | OS, | 143B |
| 2197- | SK, | Shikonin derivatives for cancer prevention and therapy |
| - | Review, | Var, | NA |
| 2225- | SK, | Shikonin protects skin cells against oxidative stress and cellular dysfunction induced by fine particulate matter |
| - | in-vitro, | Nor, | HaCaT |
| 2220- | SK, | Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt Cascades |
| - | in-vivo, | Nor, | NA |
| 2217- | SK, | Shikonin Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis to Attenuate Renal Ischemia/Reperfusion Injury by Activating the Sirt1/Nrf2/HO-1 Pathway |
| - | in-vivo, | Nor, | NA | - | in-vitro, | Nor, | HK-2 |
| 2216- | SK, | Shikonin upregulates the expression of drug-metabolizing enzymes and drug transporters in primary rat hepatocytes |
| - | in-vivo, | Nor, | NA |
| 2215- | SK, | doxoR, | Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in mice |
| - | in-vivo, | Nor, | NA |
| 2214- | SK, | Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway |
| - | in-vitro, | Nor, | NA |
| 2218- | SK, | Shikonin Alleviates Endothelial Cell Injury Induced by ox-LDL via AMPK/Nrf2/HO-1 Signaling Pathway |
| - | in-vitro, | Nor, | HUVECs |
| 3042- | SK, | The protective effects of Shikonin on lipopolysaccharide/D -galactosamine-induced acute liver injury via inhibiting MAPK and NF-kB and activating Nrf2/HO-1 signaling pathways |
| - | in-vivo, | Nor, | NA |
| 1346- | SK, | An Oxidative Stress Mechanism of Shikonin in Human Glioma Cells |
| - | in-vitro, | GBM, | U87MG | - | in-vitro, | GBM, | Hs683 |
| 2009- | SK, | Necroptosis inhibits autophagy by regulating the formation of RIP3/p62/Keap1 complex in shikonin-induced ROS dependent cell death of human bladder cancer |
| - | in-vitro, | Bladder, | NA |
| 2011- | SK, | Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β Signaling |
| - | in-vitro, | Nor, | HL7702 | - | in-vivo, | Nor, | NA |
| 1280- | SK, | Shikonin Induces Apoptotic Cell Death via Regulation of p53 and Nrf2 in AGS Human Stomach Carcinoma Cells |
| - | in-vitro, | GC, | AGS |
| 1193- | SM, | Cryptotanshinone from the Salvia miltiorrhiza Bunge Attenuates Ethanol-Induced Liver Injury by Activation of AMPK/SIRT1 and Nrf2 Signaling Pathways |
| - | in-vivo, | Alcohol, | NA | - | in-vitro, | Liver, | HepG2 |
| 4892- | Sper, | erastin, | Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer |
| - | in-vitro, | Pca, | PC3 | - | in-vivo, | Pca, | NA |
| 1688- | SSE, | Potential Role of Selenium in the Treatment of Cancer and Viral Infections |
| - | Review, | Var, | NA |
| 4727- | SSE, | Selenium inhibits ferroptosis in ulcerative colitis through the induction of Nrf2/Gpx4 |
| - | in-vivo, | Col, | NA |
| 4728- | SSE, | Selective Impact of Selenium Compounds on Two Cytokine Storm Players |
| - | NA, | Covid, | NA |
| 4723- | SSE, | Selenium Induces Ferroptosis in Colorectal Cancer Cells via Direct Interaction with Nrf2 and Gpx4 |
| - | in-vitro, | CRC, | HCT116 |
| 4733- | SSE, | Selenium supplementation of lung epithelial cells enhances nuclear factor E2-related factor 2 (Nrf2) activation following thioredoxin reductase inhibition |
| - | NA, | Nor, | NA |
| 4732- | SSE, | Selenium inhibits ferroptosis and ameliorates autistic-like behaviors of BTBR mice by regulating the Nrf2/GPx4 pathway |
| - | in-vivo, | Autism, | NA |
| 4731- | SSE, | Dietary selenium mitigates cadmium-induced apoptosis and inflammation in chicken testicles by inhibiting oxidative stress through the activation of the Nrf2/HO-1 signaling pathway |
| - | in-vivo, | Nor, | NA |
| 5096- | SSE, | Selenium Toxicity Accelerated by Out-of-Control Response of Nrf2-xCT Pathway |
| - | in-vitro, | BC, | MCF-7 |
| 3960- | Taur, | Versatile Triad Alliance: Bile Acid, Taurine and Microbiota |
| - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 3950- | Taur, | Taurine Supplementation as a Neuroprotective Strategy upon Brain Dysfunction in Metabolic Syndrome and Diabetes |
| - | Review, | Diabetic, | NA | - | Review, | Stroke, | NA | - | Review, | AD, | NA |
| 1052- | TQ, | Thymoquinone Anticancer Effects Through the Upregulation of NRF2 and the Downregulation of PD-L1 in MDA-MB-231 Triple-Negative Breast Cancer Cells |
| - | in-vitro, | BC, | MDA-MB-231 |
| - | in-vitro, | BC, | MDA-MB-231 | - | in-vitro, | BC, | MDA-MB-468 |
| 5024- | TQ, | Thymoquinone: A Tie-Breaker in SARS-CoV2-Infected Cancer Patients? |
| - | Review, | Covid, | NA |
| 2126- | TQ, | Biological and therapeutic activities of thymoquinone: Focus on the Nrf2 signaling pathway |
| - | Review, | Nor, | NA |
| 2130- | TQ, | Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model |
| - | in-vivo, | Nor, | NA |
| 2131- | TQ, | Therapeutic impact of thymoquninone to alleviate ischemic brain injury via Nrf2/HO-1 pathway |
| - | in-vitro, | Stroke, | NA | - | in-vivo, | Nor, | NA |
| 2132- | TQ, | Thymoquinone treatment modulates the Nrf2/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis |
| - | in-vivo, | Nor, | NA |
| 2133- | TQ, | CUR, | Cisplatin, | Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling |
| - | in-vitro, | Nor, | HEK293 | - | in-vivo, | NA, | NA |
| 2134- | TQ, | Modulation of Nrf2/HO1 Pathway by Thymoquinone to Exert Protection Against Diazinon-induced Myocardial Infarction in Rats |
| - | in-vivo, | Nor, | NA |
| 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 |
| 2106- | TQ, | Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy |
| - | Review, | Var, | NA |
| 3405- | TQ, | doxoR, | Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity and the underlying mechanism |
| - | vitro+vivo, | NA, | NA |
| 3410- | TQ, | Anti-inflammatory effects of thymoquinone and its protective effects against several diseases |
| - | Review, | Arthritis, | NA |
| 3409- | TQ, | Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives |
| - | in-vivo, | Nor, | NA |
| 3406- | TQ, | SeNPs, | A study to determine the effect of nano-selenium and thymoquinone on the Nrf2 gene expression in Alzheimer’s disease |
| - | in-vivo, | AD, | NA |
| 3404- | TQ, | The Neuroprotective Effects of Thymoquinone: A Review |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 3402- | TQ, | Enhanced Apoptosis in Pancreatic Cancer Cells through Thymoquinone-rich Nigella sativa L. Methanol Extract: Targeting NRF2/HO-1 and TNF-α Pathways |
| - | in-vitro, | PC, | PANC1 | - | in-vitro, | PC, | MIA PaCa-2 |
| 3401- | TQ, | Molecular mechanisms and signaling pathways of black cumin (Nigella sativa) and its active constituent, thymoquinone: a review |
| - | Review, | Var, | NA |
| 3400- | TQ, | Chemo, | Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats |
| - | in-vitro, | Nor, | NA |
| 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 |
| 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 |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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