| 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 |
| 4877- | Uro, | Urolithin-A Derivative UAS03 Improves Cognitive Deficits and Memory by Activating Nrf2 Pathways to Alleviate Oxidative Stress and Neuroinflammation |
| - | in-vivo, | AD, | NA |
| 7834- | VA, | MBS, | Neuroprotective Potential of Mung Bean (Vigna radiata L.) Polyphenols in Alzheimer's Disease: A Review |
| - | Review, | AD, | NA |
| 4311- | VitB1/Thiamine, | Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of tauopathy |
| - | in-vivo, | AD, | NA |
| 114- | VitC, | QC, | Chemoprevention of prostate cancer cells by vitamin C plus quercetin: role of Nrf2 in inducing oxidative stress |
| - | in-vitro, | Pca, | PC3 | - | in-vitro, | Pca, | DU145 |
| 2592- | VitC, | Ascorbic acid restores sensitivity to imatinib via suppression of Nrf2-dependent gene expression in the imatinib-resistant cell line |
| - | in-vitro, | CLL, | NA |
| 3108- | VitC, | QC, | The role of quercetin and vitamin C in Nrf2-dependent oxidative stress production in breast cancer cells |
| - | in-vitro, | BC, | MDA-MB-231 | - | in-vitro, | Lung, | A549 |
| 3109- | VitC, | Vitamin C Inhibited Pulmonary Metastasis through Activating Nrf2/HO-1 Pathway |
| - | in-vitro, | Lung, | H1299 |
| 3110- | VitC, | Vitamin C Attenuates Oxidative Stress, Inflammation, and Apoptosis Induced by Acute Hypoxia through the Nrf2/Keap1 Signaling Pathway in Gibel Carp (Carassius gibelio) |
| - | in-vivo, | Nor, | NA |
| 3112- | VitC, | Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid |
| - | Review, | Nor, | NA |
| 1741- | VitD3, | Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging |
| - | Review, | Var, | NA |
| 2276- | VitK2, | Vitamin K2 (MK-7) Intercepts Keap-1/Nrf-2/HO-1 Pathway and Hinders Inflammatory/Apoptotic Signaling and Liver Aging in Naturally Aging Rat |
| - | in-vivo, | Nor, | NA |
| 7913- | VT, | Review of the effects of vitexin in oxidative stress-related diseases |
| 7902- | VT, | Vitexin Protects Against Scopolamine-Induced Cognitive Impairment by Preserving Synaptic Integrity and Modulating Nrf2/HO-1 and NF-κB Signaling Pathways |
| - | in-vivo, | AD, | NA |
| 7887- | VT, | IVT, | Dietary Flavonoids Vitexin and Isovitexin: New Insights into Their Functional Roles in Human Health and Disease Prevention |
| - | Review, | AD, | NA | - | Review, | Var, | NA |
| 5015- | Xan, | PEITC, | Comparison of the Impact of Xanthohumol and Phenethyl Isothiocyanate and Their Combination on Nrf2 and NF-κB Pathways in HepG2 Cells In Vitro and Tumor Burden In Vivo |
| - | in-vitro, | HCC, | HepG2 |
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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