| 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 |
| 3660- | SFN, | Sulforaphane - role in aging and neurodegeneration |
| - | Review, | AD, | NA |
| 3659- | SFN, | Epigenetic modification of Nrf2 by sulforaphane increases the antioxidative and anti-inflammatory capacity in a cellular model of Alzheimer's disease |
| - | in-vitro, | AD, | NA |
| 3658- | SFN, | Pre-Clinical Neuroprotective Evidences and Plausible Mechanisms of Sulforaphane in Alzheimer’s Disease |
| - | Review, | AD, | NA |
| 3657- | SFN, | Sulforaphane exerts its anti-inflammatory effect against amyloid-β peptide via STAT-1 dephosphorylation and activation of Nrf2/HO-1 cascade in human THP-1 macrophages |
| - | NA, | AD, | THP1 |
| 3656- | SFN, | Chronic diseases, inflammation, and spices: how are they linked? |
| - | Review, | AD, | NA |
| 2168- | SFN, | Amelioration of Alzheimer's disease by neuroprotective effect of sulforaphane in animal model |
| - | in-vivo, | AD, | NA |
| 2555- | SFN, | Chemopreventive functions of sulforaphane: A potent inducer of antioxidant enzymes and apoptosis |
| - | Review, | Var, | NA |
| 2552- | SFN, | Chemo, | Chemopreventive activity of sulforaphane |
| - | Review, | Var, | NA |
| 2553- | SFN, | Mechanistic review of sulforaphane as a chemoprotective agent in bladder cancer |
| - | Review, | Bladder, | NA |
| 2444- | SFN, | Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage |
| - | in-vitro, | Nor, | MRC-5 |
| 2448- | SFN, | Sulforaphane and bladder cancer: a potential novel antitumor compound |
| - | Review, | Bladder, | NA |
| 1730- | SFN, | Sulforaphane: An emergent anti-cancer stem cell agent |
| - | Review, | Var, | NA |
| 1725- | SFN, | Anticancer Activity of Sulforaphane: The Epigenetic Mechanisms and the Nrf2 Signaling Pathway |
| - | Review, | Var, | NA |
| 1724- | SFN, | Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials |
| - | Review, | Var, | NA |
| 1723- | SFN, | Sulforaphane as a potential remedy against cancer: Comprehensive mechanistic review |
| - | Review, | Var, | NA |
| 1428- | SFN, | Broccoli or Sulforaphane: Is It the Source or Dose That Matters? |
| - | Review, | NA, | NA |
| 1465- | SFN, | TRAIL attenuates sulforaphane-mediated Nrf2 and sustains ROS generation, leading to apoptosis of TRAIL-resistant human bladder cancer cells |
| - | NA, | Bladder, | NA |
| 1458- | SFN, | Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma |
| - | Review, | Bladder, | NA |
| 1437- | SFN, | Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition |
| - | Review, | NA, | NA |
| 1509- | SFN, | Combination therapy in combating cancer |
| - | Review, | NA, | NA |
| 1508- | SFN, | Nrf2 targeting by sulforaphane: A potential therapy for cancer treatment |
| - | Review, | Var, | NA |
| 1501- | SFN, | The Inhibitory Effect of Sulforaphane on Bladder Cancer Cell Depends on GSH Depletion-Induced by Nrf2 Translocation |
| - | in-vitro, | CRC, | T24/HTB-9 |
| 1495- | SFN, | doxoR, | Sulforaphane protection against the development of doxorubicin-induced chronic heart failure is associated with Nrf2 Upregulation |
| - | in-vivo, | Nor, | NA |
| 1494- | SFN, | doxoR, | Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model |
| - | in-vivo, | BC, | NA | - | in-vitro, | BC, | MCF-7 | - | in-vitro, | Nor, | MCF10 |
| 1484- | SFN, | Sulforaphane’s Multifaceted Potential: From Neuroprotection to Anticancer Action |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| - | in-vitro, | Bladder, | T24/HTB-9 |
| - | in-vitro, | BrCC, | H720 | - | in-vivo, | BrCC, | NA | - | in-vitro, | BrCC, | H727 |
| 3313- | SIL, | Silymarin attenuates post-weaning bisphenol A-induced renal injury by suppressing ferroptosis and amyloidosis through Kim-1/Nrf2/HO-1 signaling modulation in male Wistar rats |
| - | in-vivo, | NA, | NA |
| 3324- | SIL, | Silymarin prevents NLRP3 inflammasome activation and protects against intracerebral hemorrhage |
| 3319- | SIL, | Silymarin and neurodegenerative diseases: Therapeutic potential and basic molecular mechanisms |
| - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 3318- | SIL, | Pharmaceutical prospects of Silymarin for the treatment of neurological patients: an updated insight |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3316- | SIL, | Chemo, | Silymarin Nanoparticles Counteract Cognitive Impairment Induced by Doxorubicin and Cyclophosphamide in Rats; Insights into Mitochondrial Dysfunction and Nrf2/HO-1 Axis |
| 3315- | SIL, | Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats |
| - | in-vivo, | Nor, | NA |
| 3312- | SIL, | Silymarin Alleviates Oxidative Stress and Inflammation Induced by UV and Air Pollution in Human Epidermis and Activates β-Endorphin Release through Cannabinoid Receptor Type 2 |
| - | Human, | Nor, | NA |
| 3302- | SIL, | Protective effects of silymarin in glioblastoma cancer cells through redox system regulation |
| - | in-vitro, | GBM, | U87MG |
| 3307- | SIL, | Flavolignans from Silymarin as Nrf2 Bioactivators and Their Therapeutic Applications |
| - | Review, | Var, | NA |
| 3308- | SIL, | Structural basis of Nrf2 activation by flavonolignans from silymarin |
| - | Analysis, | NA, | NA |
| 3309- | SIL, | Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives |
| - | Review, | NA, | NA |
| 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 |
| 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 |
| 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 |
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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