| 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 |
| 8242- | LCA, | Nrf2 signaling and autophagy are complementary in protecting lipopolysaccharide/d-galactosamine-induced acute liver injury by licochalcone A |
| - | in-vivo, | LiverDam, | NA |
| 8245- | LCA, | Licochalcone A Upregulates Nrf2 Antioxidant Pathway and Thereby Alleviates Acetaminophen-Induced Hepatotoxicity |
| - | in-vivo, | LiverDam, | NA |
| 8230- | LCA, | The Ameliorative Role of Lico A on Aflatoxin B1-Triggered Hepatotoxicity Partially by Activating Nrf2 Signal Pathway |
| - | vitro+vivo, | Nor, | NA |
| 8207- | LCA, | Licochalcone a Induces ROS-Mediated Apoptosis through TrxR1 Inactivation in Colorectal Cancer Cells |
| - | in-vitro, | CRC, | HCT116 |
| 8219- | LCA, | Licochalcone A Ameliorates Cognitive Dysfunction in an Alzheimer's Disease Model by Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis |
| - | in-vivo, | AD, | NA |
| 8222- | LCA, | Licochalcone A Induces Cholangiocarcinoma Cell Death Via Suppression of Nrf2 and NF-κB Signaling Pathways |
| - | in-vitro, | CCA, | KKU-100 | - | in-vitro, | CCA, | KKU-213 | - | in-vitro, | CCA, | KKU-214 | - | in-vitro, | CCA, | KKU-156 | - | in-vitro, | 0-Reserved, | KKU-452 |
| 8223- | LCA, | Lico A Enhances Nrf2-Mediated Defense Mechanisms against t-BHP-Induced Oxidative Stress and Cell Death via Akt and ERK Activation in RAW 264.7 Cells |
| - | in-vitro, | Nor, | RAW264.7 |
| 8224- | LCA, | 3,3',4,4'-Tetrahydroxy-2-methoxychalcone from Glycyrrhiza uralensis roots inhibits HIF-1α and Nrf2, suppressing hypoxia-induced angiogenesis |
| - | in-vitro, | CRC, | HCT116 |
| 8225- | LCA, | Cisplatin, | Licochalcone A protects against cisplatin-induced acute kidney injury via the modulation of Nrf2/Keap1-mediated ferroptosis and apoptosis |
| - | in-vivo, | Nor, | NA |
| 8229- | LCA, | Licochalcone A: a review of its pharmacology activities and molecular mechanisms |
| - | Review, | Nor, | NA |
| 8236- | LE, | Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects |
| - | Review, | Var, | NA |
| 4292- | LT, | Luteolin for neurodegenerative diseases: a review |
| - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | MS, | NA | - | Review, | Stroke, | NA |
| 4883- | LT, | CHr, | BRU, | VitC, | An update of Nrf2 activators and inhibitors in cancer prevention/promotion |
| - | Review, | Var, | NA |
| 2587- | LT, | Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs |
| - | in-vitro, | Lung, | A549 |
| 2588- | LT, | Chemo, | Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway |
| - | in-vitro, | CRC, | HCT116 |
| 2589- | LT, | Chemo, | Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway |
| - | in-vitro, | BC, | MDA-MB-231 |
| 2930- | LT, | Luteolin confers renoprotection against ischemia–reperfusion injury via involving Nrf2 pathway and regulating miR320 |
| - | in-vitro, | Nor, | NA |
| 2921- | LT, | Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies |
| - | Review, | Nor, | NA |
| 2914- | LT, | Therapeutic Potential of Luteolin on Cancer |
| - | Review, | Var, | NA |
| 2915- | LT, | Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells |
| - | in-vitro, | Colon, | HT29 | - | in-vitro, | CRC, | SNU-407 | - | in-vitro, | Nor, | FHC |
| 2919- | LT, | Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence |
| - | Review, | Var, | NA |
| 2916- | LT, | Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 2595- | LT, | Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management? |
| - | Review, | Var, | NA |
| 3828- | Lyco, | Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease |
| - | in-vitro, | AD, | M146L |
| 3531- | Lyco, | Lycopene attenuates the inflammation and apoptosis in aristolochic acid nephropathy by targeting the Nrf2 antioxidant system |
| - | in-vivo, | Nor, | NA |
| 3532- | Lyco, | Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer’s disease |
| - | in-vitro, | AD, | NA |
| 3528- | Lyco, | The Importance of Antioxidant Activity for the Health-Promoting Effect of Lycopene |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3268- | Lyco, | Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders |
| - | Review, | AD, | NA |
| 3264- | Lyco, | Pharmacological potentials of lycopene against aging and aging‐related disorders: A review |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 3275- | Lyco, | Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer |
| - | Review, | Var, | NA |
| 1709- | Lyco, | Lycopene prevents carcinogen-induced cutaneous tumor by enhancing activation of the Nrf2 pathway through p62-triggered autophagic Keap1 degradation |
| - | in-vitro, | Nor, | JB6 |
| 1708- | Lyco, | The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies |
| - | Review, | Var, | NA |
| 4230- | Lyco, | Supplementation of lycopene attenuates oxidative stress induced neuroinflammation and cognitive impairment via Nrf2/NF-κB transcriptional pathway |
| - | in-vivo, | AD, | NA |
| 4228- | Lyco, | A review for the pharmacological effect of lycopene in central nervous system disorders |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 4800- | Lyco, | Recent insights on pharmacological potential of lycopene and its nanoformulations: an emerging paradigm towards improvement of human health |
| - | Review, | Var, | NA |
| 4780- | Lyco, | Potential inhibitory effect of lycopene on prostate cancer |
| - | Review, | Pca, | NA |
| 4797- | Lyco, | A mechanistic updated overview on lycopene as potential anticancer agent |
| - | Review, | Var, | NA |
| 4795- | Lyco, | Updates on the Anticancer Profile of Lycopene and its Probable Mechanism against Breast and Gynecological Cancer |
| - | Review, | BC, | NA |
| 5252- | MAG, | Insights on the Multifunctional Activities of Magnolol |
| - | Review, | Var, | NA |
| 1780- | MEL, | Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing |
| - | Review, | Var, | NA |
| 6538- | MeSal, | ASA, | Salicylate induces AMPK and inhibits c-MYC to activate a NRF2/ARE/miR-34a/b/c cascade resulting in suppression of colorectal cancer metastasis |
| - | in-vitro, | CRC, | NA |
| 1204- | MET, | Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer |
| - | in-vitro, | Lung, | A549 | - | in-vitro, | Lung, | H1299 |
| 5785- | MET, | Metformin improves healthspan and lifespan in mice |
| - | in-vivo, | Nor, | NA |
| 4105- | MF, | Extremely low frequency electromagnetic fields stimulation modulates autoimmunity and immune responses: a possible immuno-modulatory therapeutic effect in neurodegenerative diseases |
| - | Review, | AD, | NA |
| 3457- | MF, | Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis |
| - | Review, | Var, | NA |
| 3462- | MF, | The Effect of a Static Magnetic Field on microRNA in Relation to the Regulation of the Nrf2 Signaling Pathway in a Fibroblast Cell Line That Had Been Treated with Fluoride Ions |
| - | in-vitro, | Nor, | NA |
| 3847- | MSM, | Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement |
| - | Review, | Arthritis, | NA |
| 3848- | MSM, | Modulatory effect of methylsulfonylmethane against BPA/γ-radiation induced neurodegenerative alterations in rats: Influence of TREM-2/DAP-12/Syk pathway |
| - | in-vitro, | AD, | NA |
| - | in-vitro, | AD, | NA |
| 1273- | Myr, | Myricetin Induces Ferroptosis and Inhibits Gastric Cancer Progression by Targeting NOX4 |
| - | vitro+vivo, | GC, | 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
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:% Cells:% prod#:% Target#:226 State#:% Dir#:%
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