# Hyperoside

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/hyperoside
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-03-29
**Evidence Score:** 2 / 10
**Category:** Compound
**Also Known As:** Quercetin 3-O-β-D-galactopyranoside, Quercetin 3-galactoside, Quercetin-3-O-galactoside, 3-Galactosylquercetin, Hyperin, Quercetin 3-β-D-galactopyranoside

## Overview

Hyperoside is a flavonoid glycoside composed of quercetin linked to galactose, found naturally in plants such as St. John's Wort, hawthorn, and various Hypericum species. It exerts its primary effects through [antioxidant activity](/ingredients/condition/antioxidant), modulation of the PI3K/Akt signaling pathway, and regulation of apoptotic proteins including caspases and p53.

## Health Benefits

• Anti-cancer effects in HeLa cells have been observed, involving upregulation of caspases and p53, and downregulation of Nampt and Sirt1 [Preclinical evidence]. • Shows potential [neuroprotective](/ingredients/condition/cognitive) actions via the PI3K/Akt pathway [Preclinical evidence]. • Exhibits [antioxidant activity](/ingredients/condition/antioxidant) due to hydroxyl groups, which may help in reducing oxidative stress [Preclinical evidence]. • Potential renoprotective effects are suggested by its mechanism of action [Preclinical evidence]. • Binds to 3CL protease of HCoV-229E, indicating possible [antiviral](/ingredients/condition/immune-support) properties [Preclinical evidence].

## Mechanism of Action

Hyperoside scavenges [reactive oxygen species](/ingredients/condition/antioxidant) through its hydroxyl groups on the quercetin backbone, donating electrons to neutralize free radicals. In cancer cell models, it upregulates pro-apoptotic caspase-3 and caspase-9 and tumor suppressor p53 while downregulating the NAD-biosynthetic enzyme Nampt and the deacetylase Sirt1, shifting the cell toward programmed death. [Neuroprotective effect](/ingredients/condition/cognitive)s are mediated through activation of the PI3K/Akt survival pathway, which suppresses pro-apoptotic signaling in neuronal cells under oxidative or ischemic stress.

## Clinical Summary

The current evidence base for hyperoside is derived almost entirely from in vitro cell studies and rodent models, with no completed large-scale human clinical trials specifically isolating hyperoside as an intervention. Anticancer activity has been demonstrated in HeLa cervical cancer cell lines, where hyperoside induced measurable increases in caspase activation and p53 expression. [Neuroprotective effect](/ingredients/condition/cognitive)s have been observed in mouse models of cerebral ischemia, showing reduced infarct volume and improved behavioral outcomes, though effect sizes cannot yet be extrapolated to humans. Overall, the evidence is promising but classified as preclinical, and robust randomized controlled trials in humans are absent.

## Nutritional Profile

Hyperoside (quercetin-3-O-β-D-galactoside; C21H20O12; MW 464.38 g/mol) is a flavonol glycoside, not a food or nutrient per se, and therefore does not possess a conventional macronutrient profile (no significant protein, fat, carbohydrate, or fiber contribution at pharmacologically relevant doses). Key characteristics: • Bioactive classification: Flavonoid glycoside (subclass: flavonol-O-glycoside), consisting of the aglycone quercetin linked via a β-glycosidic bond to D-galactose at the 3-position. • Natural occurrence and approximate concentrations: Found in Hypericum perforatum (St. John's Wort) leaves (~2–5 mg/g dry weight), Crataegus spp. (hawthorn) leaves and berries (~1–4 mg/g dry weight), Artemisia capillaris, Cuscuta chinensis seeds, and various Rhododendron species. Also present in lower amounts in apples, pears, and cranberries (<0.1–0.5 mg/g fresh weight). • Key functional groups: Five phenolic hydroxyl groups (positions 3', 4' on B-ring; 5, 7 on A-ring; and indirectly via the sugar moiety), which are primarily responsible for its radical-scavenging and metal-chelating [antioxidant](/ingredients/condition/antioxidant) capacity. DPPH radical scavenging IC50 is approximately 5–15 µM depending on assay conditions. • Bioavailability notes: Oral bioavailability is relatively low (estimated <5% in rodent models) due to extensive first-pass [metabolism](/ingredients/condition/weight-management). In the gut, hyperoside is hydrolyzed by intestinal β-galactosidase to release free quercetin and galactose; quercetin is then further conjugated (glucuronidation, sulfation, methylation) in enterocytes and hepatocytes. Primary circulating metabolites include quercetin-3'-O-glucuronide, isorhamnetin-3-O-glucuronide, and quercetin-3'-O-sulfate. Colonic microbiota can further degrade unabsorbed hyperoside into smaller phenolic acids (e.g., 3,4-dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid). Peak plasma concentrations of total quercetin metabolites following oral hyperoside dosing in rodents (~50–100 mg/kg) reach approximately 1–10 µM. Galactose conjugation at C-3 may confer slightly different intestinal absorption kinetics compared to quercetin-3-O-glucoside (isoquercitrin) due to substrate specificity of SGLT1 and lactase-phlorizin hydrolase. • Solubility: Moderately soluble in ethanol and methanol; poorly soluble in water (~0.6 mg/mL at 25 °C), which limits oral absorption of the intact glycoside. Solubility improves in slightly alkaline or DMSO-based formulations. • No vitamins or minerals are intrinsic to the compound itself; any associated micronutrient content would derive from the plant matrix in which hyperoside naturally occurs.

## Dosage & Preparation

There are no clinically studied dosage ranges for hyperoside in humans. Preclinical in vitro studies used concentrations of 100 μmol/L or 400 μg/mL. Consult a healthcare provider before starting any new supplement.

## Safety & Drug Interactions

Hyperoside has not been evaluated for safety in rigorous human clinical trials, so a formal adverse effect profile has not been established. Because it is structurally derived from quercetin, potential interactions with cytochrome P450 enzymes, particularly CYP3A4 and CYP2C9, are theoretically possible, which could affect [metabolism](/ingredients/condition/weight-management) of anticoagulants, statins, or immunosuppressants. Hyperoside is frequently consumed as part of St. John's Wort extracts, and any formulation containing St. John's Wort carries well-documented interactions with serotonergic drugs, oral contraceptives, and cyclosporine due to CYP and P-glycoprotein induction. Pregnant and breastfeeding individuals should avoid isolated hyperoside supplementation due to a complete lack of safety data in these populations.

## Scientific Research

No human clinical trials, RCTs, or meta-analyses on hyperoside were identified in the available sources. Evidence is limited to preclinical in vitro studies such as those conducted on HeLa cells.

## Historical & Cultural Context

No historical or traditional medicinal uses for hyperoside are documented in the available research sources.

## Synergistic Combinations

Quercetin, Rutin, Resveratrol, Curcumin, EGCG

## Frequently Asked Questions

### What is hyperoside and what plants contain it?

Hyperoside is a flavonoid glycoside formed by attaching the flavonol quercetin to the sugar galactose via a 3-O-glycosidic bond. It occurs naturally in Hypericum perforatum (St. John's Wort), hawthorn (Crataegus species), Viola tricolor, and several other medicinal plants. It is one of the marker compounds used to standardize St. John's Wort extracts alongside hypericin and hyperforin.

### Does hyperoside have anticancer properties?

Preclinical in vitro studies using HeLa cervical cancer cells have shown that hyperoside promotes apoptosis by upregulating caspase-3, caspase-9, and p53 while simultaneously downregulating the NAD-synthesizing enzyme Nampt and the sirtuin deacetylase Sirt1. This combination disrupts cellular energy metabolism and removes a brake on apoptotic signaling. However, these findings are limited to cell culture experiments and have not been validated in human clinical trials.

### How does hyperoside protect the brain?

Hyperoside activates the PI3K/Akt intracellular signaling pathway in neuronal cells, which promotes cell survival by phosphorylating and inactivating pro-apoptotic factors such as Bad and caspase-9. In rodent models of focal cerebral ischemia, hyperoside administration was associated with reduced neuronal death and smaller infarct areas. These neuroprotective effects are considered preclinical and require human trial confirmation before clinical recommendations can be made.

### What is the difference between hyperoside and quercetin?

Quercetin is a free flavonol aglycone, while hyperoside is quercetin-3-O-galactoside, meaning quercetin is bound to a galactose sugar molecule at the 3-position hydroxyl group. This glycosylation affects bioavailability, solubility, and cellular uptake, with glycosides generally showing different absorption kinetics compared to the free aglycone. Once metabolized in the gut and liver, hyperoside can release free quercetin and galactose, meaning some of its biological effects may overlap with those of quercetin itself.

### Are there any known drug interactions with hyperoside supplements?

Isolated hyperoside has no formally established drug interaction profile due to limited human pharmacokinetic data, but its quercetin backbone raises theoretical concerns about inhibition of CYP3A4 and CYP2C9 enzymes, potentially elevating plasma levels of drugs like warfarin, cyclosporine, or certain statins. When hyperoside is consumed via St. John's Wort extracts, clinically significant induction of CYP3A4 and P-glycoprotein by co-present hyperforin can reduce efficacy of oral contraceptives, antiretrovirals, and immunosuppressants. Individuals taking any prescription medication should consult a healthcare provider before using hyperoside-containing supplements.

### What is the bioavailability of hyperoside supplements and how can absorption be improved?

Hyperoside bioavailability is relatively low due to its glycoside structure, which requires gut microbiota-mediated metabolism to be converted into absorbable aglycone forms. Taking hyperoside with foods containing healthy fats or probiotics may support better absorption by enhancing gut microbial activity and intestinal permeability. The compound's poor water solubility also means absorption can vary significantly between individuals based on digestive health.

### Is hyperoside safe during pregnancy and breastfeeding?

There is insufficient clinical evidence on hyperoside safety during pregnancy and breastfeeding, so it is typically not recommended during these periods as a precautionary measure. Most flavonoid supplements are avoided during pregnancy due to potential effects on fetal development, though no specific toxicity data exists for hyperoside. Pregnant or nursing women should consult with their healthcare provider before using hyperoside supplements.

### How strong is the clinical evidence for hyperoside's health benefits in humans?

Most evidence for hyperoside comes from preclinical laboratory and animal studies, with very limited human clinical trials to date. The observed benefits in cell cultures and animal models—such as anticancer activity and neuroprotection—have not yet been conclusively demonstrated in human populations at therapeutic doses. Additional well-designed human studies are needed to establish efficacy and optimal dosing before making clinical recommendations.

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