| 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 |
| 3172- | Ash, | Implications of Withaferin A for the metastatic potential and drug resistance in hepatocellular carcinoma cells via Nrf2-mediated EMT and ferroptosis |
| - | in-vitro, | HCC, | HepG2 | - | in-vitro, | Nor, | HL7702 |
| 3156- | Ash, | Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug |
| - | Review, | Var, | NA |
| 3160- | Ash, | Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal |
| - | Review, | Var, | NA |
| 3161- | Ash, | Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage |
| - | in-vivo, | Stroke, | NA |
| 3163- | Ash, | Rad, | Withaferin A, a steroidal lactone, selectively protects normal lymphocytes against ionizing radiation induced apoptosis and genotoxicity via activation of ERK/Nrf-2/HO-1 axis |
| 3164- | Ash, | Withaferin A alleviates fulminant hepatitis by targeting macrophage and NLRP3 |
| 3166- | Ash, | Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives |
| - | Review, | Var, | NA |
| 1358- | Ash, | Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms |
| - | Review, | Var, | NA |
| 4678- | Ash, | Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer |
| - | vitro+vivo, | NSCLC, | H1975 |
| 4815- | ASTX, | The Promising Effects of Astaxanthin on Lung Diseases |
| - | Review, | Var, | NA |
| 4804- | ASTX, | Astaxanthin in cancer therapy and prevention (Review) |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 5425- | ASTX, | Multiple roles of fucoxanthin and astaxanthin against Alzheimer's disease: Their pharmacological potential and therapeutic insights |
| - | in-vivo, | AD, | NA |
| 5508- | Ba, | Neuroprotective effects of baicalin and baicalein on the central nervous system and the underlying mechanisms |
| - | Review, | Stroke, | NA | - | Review, | Park, | NA | - | Review, | AD, | NA |
| 5501- | Ba, | Therapeutic effects and mechanisms of action of Baicalein on stomach cancer: a comprehensive systematic literature review |
| - | Review, | GC, | NA |
| 4305- | Ba, | Study on the Molecular Mechanism of Baicalin Phosphorylation of Tau Protein Content in a Cell Model of Intervention Cognitive Impairment |
| - | in-vitro, | NA, | SH-SY5Y |
| 1530- | Ba, | Baicalein Decreases Hydrogen Peroxide‐Induced Damage to NG108‐15 Cells via Upregulation of Nrf2 |
| - | in-vitro, | Nor, | NG108-15 |
| 1527- | Ba, | Baicalein Alleviates Arsenic-induced Oxidative Stress through Activation of the Keap1/Nrf2 Signalling Pathway in Normal Human Liver Cells |
| - | in-vitro, | Nor, | MIHA |
| 2623- | Ba, | Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of baicalein against oxidative stress-induced DNA damage and apoptosis in HEI193 Schwann cells |
| - | in-vitro, | Nor, | HEI193 |
| 2625- | Ba, | LT, | Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocyte |
| - | in-vivo, | Stroke, | NA |
| 2627- | Ba, | Cisplatin, | Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways |
| 2617- | Ba, | Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review |
| - | Review, | Var, | NA |
| 2626- | Ba, | Molecular targets and therapeutic potential of baicalein: a review |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 2292- | Ba, | BA, | Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: A comprehensive review with future perspectives |
| - | Review, | Var, | NA |
| 2296- | Ba, | The most recent progress of baicalein in its anti-neoplastic effects and mechanisms |
| - | Review, | Var, | NA |
| 5536- | BBM, | Regulation of Cell-Signaling Pathways by Berbamine in Different Cancers |
| - | Review, | Var, | NA |
| 5551- | BBM, | Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-κB Axis |
| - | vitro+vivo, | Bladder, | NA |
| - | in-vivo, | Stroke, | NA |
| 2021- | BBR, | Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways |
| - | Review, | NA, | NA |
| 1385- | BBR, | 5-FU, | Low-Dose Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents via Induction of Autophagy and Antioxidation |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | MDA-MB-231 |
| 1392- | BBR, | Based on network pharmacology and experimental validation, berberine can inhibit the progression of gastric cancer by modulating oxidative stress |
| - | in-vitro, | GC, | AGS | - | in-vitro, | GC, | MKN45 |
| 1389- | BBR, | Lap, | Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS |
| - | in-vitro, | BC, | BT474 | - | in-vitro, | BC, | AU-565 |
| 1380- | BBR, | doxoR, | treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358. |
| - | in-vivo, | Nor, | NA |
| 3678- | BBR, | Network pharmacology study on the mechanism of berberine in Alzheimer’s disease model |
| - | Review, | AD, | NA |
| 5633- | BCA, | Mechanisms Behind the Pharmacological Application of Biochanin-A: A review |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 2725- | BetA, | Betulinic acid protects against renal damage by attenuation of oxidative stress and inflammation via Nrf2 signaling pathway in T-2 toxin-induced mice |
| - | in-vivo, | Nor, | NA |
| 2757- | BetA, | Betulinic Acid Inhibits Glioma Progression by Inducing Ferroptosis Through the PI3K/Akt and NRF2/HO-1 Pathways |
| - | in-vitro, | GBM, | U251 |
| 2758- | BetA, | Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway |
| - | in-vivo, | Nor, | NA |
| 2759- | BetA, | Chemopreventive and Chemotherapeutic Potential of Betulin and Betulinic Acid: Mechanistic Insights From In Vitro, In Vivo and Clinical Studies |
| - | Review, | Var, | NA |
| 2756- | BetA, | Betulinic acid inhibits growth of hepatoma cells through activating the NCOA4-mediated ferritinophagy pathway |
| - | in-vitro, | HCC, | HUH7 | - | in-vitro, | HCC, | H1299 |
| 5686- | BJ, | BRU, | A review of Brucea javanica: metabolites, pharmacology and clinical application |
| - | Review, | Var, | NA |
| 5690- | BJ, | BRU, | Brusatol: A potential sensitizing agent for cancer therapy from Brucea javanica |
| - | Review, | Var, | NA |
| 3517- | Bor, | Se, | The protective effects of selenium and boron on cyclophosphamide-induced hepatic oxidative stress, inflammation, and apoptosis in rats |
| - | in-vivo, | Nor, | NA |
| 3510- | Bor, | Boron Affects the Development of the Kidney Through Modulation of Apoptosis, Antioxidant Capacity, and Nrf2 Pathway in the African Ostrich Chicks |
| - | in-vivo, | Nor, | NA |
| 3511- | Bor, | Boron |
| - | Review, | NA, | NA |
| 3513- | Bor, | Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status |
| - | in-vitro, | Pca, | DU145 | - | in-vitro, | Nor, | MEF |
| 3524- | Bor, | Boric Acid Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice |
| 738- | Bor, | Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways |
| - | in-vitro, | GBM, | U251 | - | in-vitro, | GBM, | A172 | - | in-vitro, | Nor, | SVGp12 |
| 726- | Bor, | Redox Mechanisms Underlying the Cytostatic Effects of Boric Acid on Cancer Cells—An Issue Still Open |
| - | Review, | NA, | NA |
| 4272- | Bor, | Neuroprotective properties of borax against aluminum hydroxide-induced neurotoxicity: Possible role of Nrf-2/BDNF/AChE pathways in fish brain |
| 3866- | Bos, | Mechanistic role of boswellic acids in Alzheimer's disease: Emphasis on anti-inflammatory properties |
| - | Review, | AD, | 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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