# Rhoifolin

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/rhoifolin
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-03-31
**Evidence Score:** 4 / 10
**Category:** Compound
**Also Known As:** Apigenin-7-O-rhoinoside, Apigenin-7-O-rhamnoside, 7-O-rhamnosylapigenin, Apigenin 7-rhamnoside, Rhoifoloside

## Overview

Rhoifolin is a flavone glycoside found in citrus fruits, grapefruit leaves, and Rhus succedanea that exerts anti-inflammatory and antioxidant effects primarily by inhibiting [pro-inflammatory cytokine](/ingredients/condition/inflammation) pathways and scavenging [reactive oxygen species](/ingredients/condition/antioxidant). Its apigenin-7-O-neohesperidoside structure allows it to modulate NF-κB signaling and upregulate endogenous antioxidant enzymes including superoxide dismutase and [glutathione](/ingredients/condition/detox).

## Health Benefits

• [Anti-inflammatory](/ingredients/condition/inflammation) effects: Reduced paw edema by 14-45% in rat models (preliminary evidence)
• [Antioxidant activity](/ingredients/condition/antioxidant): Increased [glutathione](/ingredients/condition/detox) and superoxide dismutase while decreasing oxidative stress markers in arthritic rats (preliminary evidence)
• Anti-rheumatoid arthritis potential: 10-20 mg/kg daily showed effects comparable to indomethacin in rat models (preliminary evidence)
• Anticancer properties: Demonstrated cytotoxicity against cancer cell lines with IC50 values of 5.9-6.2 μg/mL for certain cancers (in vitro evidence only)
• Blood sugar regulation: Modulated glucokinase and glucose-6-phosphatase in diabetes models (preliminary animal evidence)

## Mechanism of Action

Rhoifolin inhibits the NF-κB signaling pathway, thereby suppressing downstream production of [pro-inflammatory cytokine](/ingredients/condition/inflammation)s such as TNF-α, IL-1β, and IL-6 that drive inflammatory cascades. It also scavenges [reactive oxygen species](/ingredients/condition/antioxidant) directly and upregulates endogenous antioxidant enzymes—specifically superoxide dismutase (SOD) and [glutathione](/ingredients/condition/detox) (GSH)—while reducing malondialdehyde (MDA) and nitric oxide levels as markers of oxidative stress. Additionally, its apigenin aglycone core may inhibit cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, contributing to its observed anti-edema effects.

## Clinical Summary

Current evidence for rhoifolin is limited exclusively to preclinical in vitro and rodent in vivo studies, with no published human clinical trials to date. In rat models of carrageenan-induced paw edema, oral or intraperitoneal administration of rhoifolin reduced edema by 14-45% depending on dose and time point. In adjuvant-induced arthritic rat models, doses of 10-20 mg/kg demonstrated significant reductions in [oxidative stress](/ingredients/condition/antioxidant) markers alongside restored SOD and [glutathione](/ingredients/condition/detox) levels. These findings are promising but cannot be extrapolated to humans without controlled clinical trial data.

## Nutritional Profile

Rhoifolin (apigenin-7-O-neohesperidoside; C₂₇H₃₀O₁₄, MW 578.52 g/mol) is a flavone glycoside, not a macronutrient source. It provides no significant calories, protein, fat, fiber, or essential vitamins/minerals at bioactive doses. Key biochemical characteristics: • Classification: Apigenin disaccharide conjugate (neohesperidoside — rhamnose-glucose linkage at the 7-position of apigenin). • Natural concentrations in food sources: Found in citrus fruits (grapefruit, bitter orange), tomatoes, artichokes, and banana sheaths, typically at low mg/kg levels (e.g., ~5–50 mg/kg fresh weight in citrus peel extracts; trace to ~10 mg/kg in tomato leaves). • Bioactive compound profile: Acts as a polyphenolic [antioxidant](/ingredients/condition/antioxidant) with reported IC₅₀ values for DPPH radical scavenging in the range of ~15–50 µM depending on assay conditions; inhibits [NF-κB](/ingredients/condition/inflammation) and COX-2 pathways at micromolar concentrations in vitro. • Bioavailability notes: Oral bioavailability is considered low to moderate, as the neohesperidoside sugar moiety must be cleaved by intestinal β-glucosidases and gut microbiota to release the aglycone apigenin for absorption. The glycoside form is more water-soluble (estimated aqueous solubility ~0.5–1.0 mg/mL) than free apigenin but is subject to extensive first-pass [metabolism](/ingredients/condition/weight-management). Colonic microbiota-mediated hydrolysis is a major route for generating bioavailable apigenin and smaller phenolic metabolites (e.g., p-coumaric acid, phloroglucinol derivatives). Plasma concentrations after oral dosing in animal models (10–20 mg/kg) are generally in the low nanomolar to low micromolar range. Co-administration with lipids or formulation in nanoparticles has been explored to enhance absorption. • No established Daily Value or Recommended Dietary Allowance exists; studied doses in rat models range from 10–20 mg/kg body weight/day. Equivalent human doses (estimated by allometric scaling) would approximate 1.6–3.2 mg/kg/day, though human pharmacokinetic data remain limited.

## Dosage & Preparation

Animal studies used oral doses of 10-20 mg/kg daily in rat models, with some studies testing up to 250 mg/kg. No human dosage data or standardized extract forms are available. Consult a healthcare provider before starting any new supplement.

## Safety & Drug Interactions

No human safety data, established tolerable upper intake levels, or clinical adverse event profiles currently exist for isolated rhoifolin supplementation. Based on its structural similarity to other flavone glycosides, mild gastrointestinal discomfort is plausible at high doses. Rhoifolin may theoretically potentiate the effects of anticoagulant or anti-platelet drugs such as warfarin due to flavonoid-class interactions with CYP450 enzymes, though this has not been directly studied. Pregnant or breastfeeding individuals and those on immunosuppressive or [anti-inflammatory](/ingredients/condition/inflammation) medications should avoid rhoifolin supplements until safety data are established.

## Scientific Research

Current evidence is limited to preclinical studies with no human clinical trials identified. Key research includes a rat rheumatoid arthritis model (PMID: 32401927) where 10-20 mg/kg oral rhoifolin daily for one month significantly reduced [inflammation](/ingredients/condition/inflammation) and [oxidative stress](/ingredients/condition/antioxidant) markers. In vitro studies demonstrated anticancer effects through apoptosis induction and migration inhibition.

## Historical & Cultural Context

While rhoifolin occurs in traditionally used plants like Plumula Nelumbinis and Teucrium polium, there is no documented historical use of isolated rhoifolin itself. Research notes its testing for anti-arthritic effects as novel, suggesting it lacks established traditional medicinal applications as an isolated compound.

## Synergistic Combinations

Other flavonoids, [antioxidant](/ingredients/condition/antioxidant)s like [glutathione](/ingredients/condition/detox), [anti-inflammatory](/ingredients/condition/inflammation) compounds, traditional arthritis herbs

## Frequently Asked Questions

### What is rhoifolin and what foods contain it?

Rhoifolin is a flavone glycoside chemically identified as apigenin-7-O-neohesperidoside, naturally occurring in grapefruit peel, citrus leaves, Rhus succedanea, and certain herbs including Cirsium japonicum. It belongs to the broader flavonoid family and is most concentrated in the leaves and rind of citrus species rather than the fruit pulp itself.

### Does rhoifolin reduce inflammation?

Preclinical rodent studies show rhoifolin reduced carrageenan-induced paw edema by 14-45% at various doses, suggesting meaningful anti-inflammatory activity. This effect is attributed to inhibition of NF-κB signaling and suppression of inflammatory cytokines including TNF-α and IL-1β, as well as possible COX and LOX enzyme inhibition. However, no human clinical trials have confirmed these effects in people.

### What is the studied dosage of rhoifolin in animal research?

In rat models of rheumatoid arthritis and oxidative stress, the most frequently studied dose range is 10-20 mg/kg of body weight administered orally or intraperitoneally. These doses produced measurable reductions in edema, inflammatory markers, and oxidative stress indicators including malondialdehyde. No equivalent human dosage has been established since no clinical trials have been conducted.

### Can rhoifolin help with arthritis?

Animal studies using adjuvant-induced arthritis models show that rhoifolin at 10-20 mg/kg reduced joint inflammation and restored antioxidant enzyme levels including superoxide dismutase and glutathione while decreasing oxidative stress markers. These results suggest potential anti-rheumatoid arthritis activity mechanistically linked to NF-κB and cytokine suppression. No human clinical data exist, so rhoifolin cannot currently be recommended as an arthritis treatment.

### Is rhoifolin safe to take as a supplement?

There are no published human clinical trials evaluating the safety, pharmacokinetics, or tolererable dosage of isolated rhoifolin, meaning no evidence-based safety profile exists for supplemental use. Its flavone glycoside structure suggests a low acute toxicity risk similar to related compounds like apigenin, but potential interactions with CYP450-metabolized drugs such as warfarin or statins cannot be ruled out. Individuals who are pregnant, breastfeeding, or taking prescription medications should consult a healthcare provider before using any rhoifolin-containing supplement.

### How does rhoifolin compare to other natural anti-inflammatory compounds like quercetin or curcumin?

Rhoifolin is a flavanone glycoside structurally related to other plant polyphenols, but direct comparative human studies are lacking. Preliminary animal data suggests rhoifolin may reduce joint inflammation comparably to indomethacin, though quercetin and curcumin have more extensive clinical evidence in humans. The choice between these compounds depends on individual tolerance, bioavailability differences, and specific health goals, as each may work through partially overlapping but distinct antioxidant and anti-inflammatory pathways.

### What is the current state of clinical research on rhoifolin in humans?

Clinical research on rhoifolin in humans is extremely limited; most evidence comes from in vitro and animal studies in rats and mice. While animal models show promising anti-inflammatory and antioxidant effects at 10-20 mg/kg doses, no large-scale human trials have established safe or effective dosages for supplement use. More rigorous human clinical trials are needed before rhoifolin can be recommended as a standalone therapeutic agent.

### Does rhoifolin require specific conditions for optimal absorption and effectiveness?

Rhoifolin is a glycoside form of the aglycone diosmetin, and its bioavailability may depend on gut microbiota that can cleave the sugar moiety for better absorption. Like other plant polyphenols, rhoifolin absorption may be enhanced when consumed with dietary fats and may be affected by individual differences in digestive enzyme activity and microbiome composition. However, human pharmacokinetic studies on rhoifolin are lacking, so optimal intake timing and food pairing recommendations cannot be definitively stated.

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*Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com*
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