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| Hyperoside is a chemical compound and a quercetin galactoside. It is found in various plants and has antibacterial, antifungal and UV blocking properties. Hyperoside is an active ingredient in plants, such as Hypericum monogynum in Hypericaceae, Crataegus pinnatifida in Rosaceae and Polygonum aviculare in Polygonaceae. Hyperoside is a natural flavonol glycoside in various plants, such as Crataegus pinnatifida Bge, Forsythia suspensa, and Cuscuta chinensis Lam. **-Note NRF2 up in normal cells and down in cancer cells** -not currently available as supplement, but it is in Hawthorn Extract. (Natural factors lists it as hyperoside equilvalents 6.6mg/300mg) Hyperoside — also known as hyperin and quercetin-3-O-β-D-galactoside, is a naturally occurring flavonol glycoside consisting of quercetin conjugated at the 3-position to β-D-galactose. It is found in numerous medicinal and dietary plants including species of Hypericum, Crataegus, Polygonum, and Rhododendron. It is classified as a plant-derived flavonoid/polyphenolic small molecule. Hyperoside has antioxidant and cytoprotective activity in many normal-cell models but can produce cancer-selective stress responses, apoptosis, autophagy, and ferroptosis depending on tumor type and concentration. Its aglycone is quercetin. Primary mechanisms (ranked):
Bioavailability / PK relevance: Oral bioavailability of intact hyperoside appears poor. Rat studies found very low systemic exposure after intragastric administration, with substantially greater exposure after parenteral administration. Hyperoside is relatively resistant to gastrointestinal hydrolysis compared with isoquercitrin, which may limit absorption of its quercetin aglycone. Distribution studies indicate preferential accumulation in kidney relative to several other organs. Nanoparticle and liposomal formulations have therefore been investigated to improve delivery and tumor or mitochondrial accumulation. Long-term high-dose exposure warrants caution because renal toxicity has been reported preclinically. In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 µM hyperoside, while some autophagy studies have used 0.5–2 mM. These concentrations, particularly the millimolar experiments, are unlikely to represent achievable concentrations of unchanged hyperoside following conventional oral administration. Consequently, direct translation of many in-vitro anticancer effects to oral supplementation is weak without an exposure-enhancing formulation. Clinical evidence status: Preclinical. Anticancer activity has been demonstrated in multiple cancer-cell systems and several mouse xenograft or chemically induced tumor models, including lung, breast, pancreatic, skin, liver, colorectal, esophageal, and hematologic malignancy models. There is currently no established human anticancer efficacy, approved oncology indication, or convincing interventional clinical evidence for purified hyperoside. FDA substance registration identifies hyperoside chemically but does not constitute drug approval. Hyperoside Cancer-Relevant Mechanisms
Hyperoside and Alzheimer's disease: Hyperoside has significant preclinical neuroprotective evidence in Alzheimer's disease models. Long-term administration in APP/PS1 transgenic mice improved spatial learning and memory and reduced amyloid plaque deposition, tau phosphorylation, activated microglia and astrocytes, neuroinflammation, and oxidative stress. Mechanistic evidence implicates suppression of BACE1 and GSK-3β, protection of the blood-brain barrier, inhibition of mitochondrial and caspase-dependent apoptosis, and broader antioxidant/anti-inflammatory effects. Evidence remains preclinical; clinical efficacy in human Alzheimer's disease has not been established. Hyperoside Alzheimer's-Relevant Mechanisms
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| 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 |
| 7565- | HYP, | Potential Implications of Hyperoside on Oxidative Stress-Induced Human Diseases: A Comprehensive Review |
| - | Review, | AD, | NA |
| 7563- | HYP, | Hyperoside alleviates macrophages and microglia-mediated neuroinflammation and oxidative stress through activating PI3K/AKT and Nrf2/HO-1 signaling pathway post spinal cord injury |
| - | vitro+vivo, | Nor, | NA |
| 7562- | HYP, | doxoR, | Hyperoside Inhibits Doxorubicin-Induced Ferroptosis in Cardiomyocytes via the Nrf2/GPX4 Pathway |
| - | in-vivo, | Nor, | NA |
| 7561- | HYP, | Hyperoside Exerts Therapeutic Effects on Parkinson's Disease by Mitigating Oxidative Stress through Activation of Nrf2/HO-1 Pathway |
| - | in-vivo, | Park, | NA |
| 7558- | HYP, | The Cytoprotective Effect of Hyperoside against Oxidative Stress Is Mediated by the Nrf2-ARE Signaling Pathway through GSK-3β Inactivation |
| - | in-vivo, | AD, | NA |
| 7546- | HYP, | Hyperoside attenuates hydrogen peroxide-induced L02 cell damage via MAPK-dependent Keap₁-Nrf₂-ARE signaling pathway |
| - | in-vitro, | Nor, | L02 |
| 7545- | HYP, | Hyperoside induces ferroptosis in chronic myeloid leukemia cells by targeting NRF2 |
| - | in-vitro, | CML, | K562 |
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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