| 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 |
| Normal Healthy |
| - | vitro+vivo, | Nor, | NA |
| 4561- | AgNPs, | VitC, | Cellular Effects Nanosilver on Cancer and Non-cancer Cells: Potential Environmental and Human Health Impacts |
| - | in-vitro, | CRC, | HCT116 | - | in-vitro, | Nor, | HEK293 |
| 1235- | ALA, | Cisplatin, | α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway |
| - | in-vitro, | Nor, | HEI-OC1 | - | ex-vivo, | NA, | NA |
| 1561- | Api, | Apigenin Reactivates Nrf2 Anti-oxidative Stress Signaling in Mouse Skin Epidermal JB6 P + Cells Through Epigenetics Modifications |
| - | in-vivo, | Nor, | JB6 |
| 2318- | Api, | Apigenin as a multifaceted antifibrotic agent: Therapeutic potential across organ systems |
| - | Review, | Nor, | NA |
| 3388- | ART/DHA, | Keap1 Cystenine 151 as a Potential Target for Artemisitene-Induced Nrf2 Activation |
| - | in-vitro, | Lung, | A549 | - | in-vitro, | Nor, | GP-293 | - | in-vitro, | BC, | MDA-MB-231 |
| 4991- | ART/DHA, | doxoR, | Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy |
| - | in-vivo, | Nor, | H9c2 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 1425- | Bos, | Protective Effect of Boswellic Acids against Doxorubicin-Induced Hepatotoxicity: Impact on Nrf2/HO-1 Defense Pathway |
| - | in-vivo, | Nor, | NA |
| 5872- | CA, | Nrf2/ARE-Mediated Antioxidant Actions of Pro-Electrophilic Drugs |
| - | Review, | Nor, | NA |
| 5873- | CA, | Carnosic acid serves as a dual Nrf2 activator and PTEN/AKT suppressor to inhibit traumatic heterotopic ossification |
| - | vitro+vivo, | Nor, | NA |
| 2394- | CAP, | Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction |
| - | in-vitro, | Nor, | GES-1 |
| 5766- | CAPE, | A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model |
| - | in-vivo, | Nor, | NA |
| 5900- | CAR, | TV, | Lights and Shadows of Essential Oil-Derived Compounds: Antimicrobial and Anti-Inflammatory Properties of Eugenol, Thymol, Cinnamaldehyde, and Carvacrol |
| - | Review, | Nor, | NA |
| 5926- | CAR, | An Updated Review of Research into Carvacrol and Its Biological Activities |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | asthmatic, | NA |
| 5928- | Catechins, | Bioavailability of Tea Catechins and Its Improvement |
| - | Review, | Nor, | NA |
| 6010- | CGA, | The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review |
| - | Review, | Nor, | NA |
| 6011- | CGA, | Chlorogenic Acid’s Role in Metabolic Health: Mechanisms and Therapeutic Potential |
| - | Review, | Nor, | NA |
| 2807- | CHr, | Evidence-based mechanistic role of chrysin towards protection of cardiac hypertrophy and fibrosis in rats |
| - | in-vivo, | Nor, | NA |
| 5798- | CRMs, | Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders |
| - | Review, | Nor, | NA | - | Review, | AD, | NA |
| 2272- | dietMet, | Methionine restriction - Association with redox homeostasis and implications on aging and diseases |
| - | Review, | Nor, | NA |
| 3221- | EGCG, | EGCG upregulates phase-2 detoxifying and antioxidant enzymes via the Nrf2 signaling pathway in human breast epithelial cells |
| - | in-vitro, | Nor, | MCF10 |
| 3210- | EGCG, | Protective effect of epigallocatechin-3-gallate (EGCG) via Nrf2 pathway against oxalate-induced epithelial mesenchymal transition (EMT) of renal tubular cells |
| - | in-vitro, | Nor, | NA |
| 3214- | EGCG, | EGCG-induced selective death of cancer cells through autophagy-dependent regulation of the p62-mediated antioxidant survival pathway |
| - | in-vitro, | Nor, | MRC-5 | - | in-vitro, | Cerv, | HeLa | - | in-vitro, | Nor, | HEK293 | - | in-vitro, | BC, | MDA-MB-231 | - | in-vitro, | CRC, | HCT116 |
| 1974- | EGCG, | Protective Effect of Epigallocatechin-3-Gallate in Hydrogen Peroxide-Induced Oxidative Damage in Chicken Lymphocytes |
| - | in-vitro, | Nor, | NA |
| 2861- | FIS, | The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress |
| - | Review, | Nor, | NA | - | Review, | Stroke, | NA | - | Review, | Park, | NA |
| 1635- | HCA, | Hydroxycitric acid prevents hyperoxaluric-induced nephrolithiasis and oxidative stress via activation of the Nrf2/Keap1 signaling pathway |
| - | vitro+vivo, | Nor, | NA |
| 1638- | HCAs, | Anticancer potential of hydroxycinnamic acids: mechanisms, bioavailability, and therapeutic applications |
| - | Review, | Nor, | NA |
| 2873- | HNK, | Honokiol Alleviates Oxidative Stress-Induced Neurotoxicity via Activation of Nrf2 |
| - | in-vitro, | Nor, | PC12 |
| 2871- | HNK, | Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling |
| - | in-vivo, | Nor, | NA |
| 2921- | LT, | Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies |
| - | Review, | Nor, | 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 |
| 3531- | Lyco, | Lycopene attenuates the inflammation and apoptosis in aristolochic acid nephropathy by targeting the Nrf2 antioxidant system |
| - | in-vivo, | Nor, | NA |
| 3528- | Lyco, | The Importance of Antioxidant Activity for the Health-Promoting Effect of Lycopene |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | Park, | 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 |
| 5785- | MET, | Metformin improves healthspan and lifespan in mice |
| - | in-vivo, | Nor, | 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 |
| 1680- | PBG, | Protection against Ultraviolet A-Induced Skin Apoptosis and Carcinogenesis through the Oxidative Stress Reduction Effects of N-(4-bromophenethyl) Caffeamide, a Propolis Derivative |
| - | in-vitro, | Nor, | HS68 |
| 3254- | PBG, | Brazilian green propolis water extract up-regulates the early expression level of HO-1 and accelerates Nrf2 after UVA irradiation |
| - | in-vitro, | Nor, | NA |
| 3251- | PBG, | The Antioxidant and Anti-Inflammatory Effects of Flavonoids from Propolis via Nrf2 and NF-κB Pathways |
| - | Review, | AD, | NA | - | Review, | Diabetic, | NA | - | Review, | Var, | NA | - | in-vitro, | Nor, | H9c2 |
| 3253- | PBG, | Brazilian red propolis extract enhances expression of antioxidant enzyme genes in vitro and in vivo |
| - | in-vitro, | Nor, | HEK293 | - | in-vivo, | Nor, | NA |
| 5016- | PEITC, | Phenethyl Isothiocyanate (PEITC) interaction with Keap1 activates the Nrf2 pathway and inhibits lipid accumulation in adipocytes |
| - | in-vitro, | 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
Filter Conditions: Pro/AntiFlg:% IllCat:% CanType:49 Cells:% prod#:% Target#:226 State#:% Dir#:2
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