Rhamnetin

Rhamnetin at a Glance

Rhamnetin is a naturally occurring methylated flavonol — quercetin carrying a single methyl group on the 7-position of its A-ring, hence its systematic name 7-O-methylquercetin. It occurs as a minor constituent, usually stored as glycosides, in clove buds and in the berries of Rhamnus (buckthorn), the genus that gives the molecule its name ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}.

It sits between two better-known relatives. Its parent is quercetin; its structural isomer is isorhamnetin, which carries the same lone methyl group but on the 3′-position of the B-ring rather than the 7-position of the A-ring. Where that methyl group sits changes the molecule’s antioxidant chemistry and metabolism, so rhamnetin is not interchangeable with either — a distinction worth holding onto, because flavonol data are routinely mixed up.

Like most minor flavonols, rhamnetin’s applied literature is entirely preclinical. A 2022 review catalogues antioxidant, anti-inflammatory, anticancer, antiviral and antibacterial activity, all from cell and animal models, and notes that its toxicology is only lightly characterised ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}. There is no trial of the isolated molecule in humans.

Rhamnetin vs. Quercetin & Isorhamnetin

The point is one methyl group. Rhamnetin, quercetin and isorhamnetin share the same flavonol skeleton and differ only in whether — and where — a hydroxyl has been methylated:

• Quercetin — the fully hydroxylated parent, with free hydroxyls at the 3, 5, 7, 3′ and 4′ positions. Its catechol B-ring (the 3′,4′-dihydroxy pair) is the main engine of its radical-scavenging chemistry.
• Rhamnetin — 7-O-methylquercetin. The methyl caps the A-ring 7-hydroxyl, leaving the catechol B-ring intact. The 3-hydroxyl on the C-ring is retained, which reviewers link to its anti-inflammatory and enzyme-inhibitory behaviour ^{1,3Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →Reference 3Park ES et al. · 2014In vitroCardioprotective effects of rhamnetin in H9c2 cardiomyoblast cells under H₂O₂-induced apoptosis — in vitroView study →}.
• Isorhamnetin — 3′-O-methylquercetin. Here the methyl caps one hydroxyl of the B-ring catechol, changing antioxidant potency and blocking a site otherwise used for metabolic conjugation.

Methylation generally trades some raw antioxidant potency for greater metabolic stability and membrane permeability. Because rhamnetin methylates the A-ring rather than the B-ring, it keeps the catechol that drives quercetin-type scavenging, distinguishing its profile from isorhamnetin’s. In practice, though, the three are frequently studied side by side, and much of rhamnetin’s reputation is inferred from the flavonol class rather than demonstrated for the molecule itself ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}.

What It's Used For

Rhamnetin’s evidence is preclinical and mechanism-led. The most developed signal is anticancer radiosensitization, which has the only in-vivo (xenograft) data; the rest are cell-culture studies, and antioxidant activity underpins most of them.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Scores are held low because there is no isolated-rhamnetin human trial; each row is preclinical. Each application links to its write-up.

01Anticancer / radiosensitizationShaky32%Isolated rhamnetin; NSCLC cells + miR-34a/Notch-1 mechanism + mouse xenograft ^{2Reference 2Kang J et al. · 2013In vitroRhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (EMT) by miR-34a-mediated suppression of Notch-1 expression in non-small cell lung cancer cell lines — in vitro + xenograftView study →}

02Antioxidant / cardioprotectiveShaky28%Isolated rhamnetin; H9c2 cardiomyoblast oxidative-stress model ^{3Reference 3Park ES et al. · 2014In vitroCardioprotective effects of rhamnetin in H9c2 cardiomyoblast cells under H₂O₂-induced apoptosis — in vitroView study →}

03Anti-inflammatoryShaky24%Isolated rhamnetin; sPLA2 enzyme inhibition + review ^{1,5Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →Reference 5Novo Belchor M et al. · 2017In vitroEvaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2 — in vitroView study →}

04Hepatic / metabolicShaky20%Isolated rhamnetin; HepG2 NASH/HCC cell model ^{4Reference 4Shatta MA et al. · 2023In vitroRhamnetin ameliorates non-alcoholic steatosis and hepatocellular carcinoma in vitro — in vitroView study →}

05Antiviral / antibacterialShaky14%Review-level only; no primary isolate study verified here ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}

Mechanisms

The A-ring (7-position) methylation is the structural signature: it caps one hydroxyl while leaving the B-ring catechol intact, so rhamnetin keeps quercetin-type scavenging chemistry that its B-ring-methylated isomer isorhamnetin partly loses ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}.

Pharmacokinetics

Dedicated human pharmacokinetic data for rhamnetin are sparse. As a methylated flavonol it is expected to behave broadly like its class: in plants it occurs largely as glycosides that must be hydrolysed before absorption, and the free aglycone is subject to extensive phase-II conjugation (glucuronidation and sulfation) that keeps circulating levels of the parent low. Methylation of the 7-hydroxyl removes one conjugation site and raises lipophilicity, which — as for isorhamnetin relative to quercetin — is generally associated with somewhat improved membrane permeability and metabolic stability, but not with high oral bioavailability ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}. The practical consequence mirrors the other flavonols: the low-micromolar concentrations effective in cell studies are not trivially reached in plasma from dietary or supplemental intake, which tempers every downstream claim. Quantitative absorption, bioavailability and half-life figures for the isolated molecule are not well characterised.

Clinical Trials

There are no registered trials of isolated rhamnetin. Its only human relevance is indirect — as one of many minor flavonols in clove and buckthorn preparations, which are plant exposures that cannot be read as rhamnetin results. Everything here is preclinical.

Last checked: July 2026.

Isolate vs. Plant Studies

Unusually for this database, rhamnetin’s applied evidence is almost all isolated-molecule work — the radiosensitization, cardiomyoblast, sPLA2 and hepatic studies all tested the pure compound in defined systems ^{2,3,4,5Reference 2Kang J et al. · 2013In vitroRhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (EMT) by miR-34a-mediated suppression of Notch-1 expression in non-small cell lung cancer cell lines — in vitro + xenograftView study →Reference 3Park ES et al. · 2014In vitroCardioprotective effects of rhamnetin in H9c2 cardiomyoblast cells under H₂O₂-induced apoptosis — in vitroView study →Reference 4Shatta MA et al. · 2023In vitroRhamnetin ameliorates non-alcoholic steatosis and hepatocellular carcinoma in vitro — in vitroView study →Reference 5Novo Belchor M et al. · 2017In vitroEvaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2 — in vitroView study →}. That is a genuine strength for interpreting mechanism: the effects are attributable to rhamnetin, not to a complex extract. The weakness lies elsewhere — the studies are in-vitro or single-model rodent, at concentrations the molecule’s limited bioavailability makes hard to reach by mouth. When rhamnetin appears inside a whole herb such as clove, it is one minor flavonol among dozens of constituents (dominated by eugenol and the tannin/phenolic fraction), so a clove or buckthorn preparation’s effects should never be attributed to rhamnetin alone ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}.

Prevalence in Nature

Rhamnetin is a minor, sporadically distributed flavonol rather than a bulk dietary compound. Its classic sources are the berries of Rhamnus (buckthorn), from which its name derives, and the dried flower buds of clove (Syzygium aromaticum), where it is one of the flavonoids of the non-volatile fraction ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}. It is reported at low levels in a scatter of other fruits and vegetables, generally stored as glycosides (for example rhamnetin-3-glycosides) that release the aglycone on hydrolysis. Quantitative concentrations are not well documented, so a comparative content chart is not yet possible — the missing figures are tracked in this compound’s gaps note.

Discovery & Synthesis

Rhamnetin has long been recognised as the 7-O-methyl ether of quercetin, and it takes its name from the genus Rhamnus (buckthorn), a classic botanical source. First-isolation specifics and a first total synthesis are not well documented in sources verified here. The molecule is readily prepared semi-synthetically from quercetin by regioselective methylation: a 2010 method built quercetin tetraesters as intermediates to introduce the 7-position methyl selectively and obtained rhamnetin in high yield ^{6Reference 6Mattarei A et al. · 2010Regioselective O-derivatization of quercetin via ester intermediatesView study →}. Because quercetin is cheap and abundant, partial methylation is a practical route to research-grade rhamnetin, alongside extraction from plant material.

Patents: not yet researched.

Toxicity & Safety

Rhamnetin carries a low toxicity flag. It is a minor dietary flavonol consumed at trace levels in foods such as cloves, and the studies that have tested it describe it as well tolerated in their models — notably, the sPLA2 study reported enzyme inhibition without cellular toxicity ^{5Reference 5Novo Belchor M et al. · 2017In vitroEvaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2 — in vitroView study →}. The 2022 pharmacology review, however, explicitly notes that comprehensive toxicology data remain limited and calls for further investigation, so the low flag reflects the absence of alarming findings and food-level exposure rather than a completed safety dossier ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}.

Safety at a Glance

✅ Low / no toxicity

• Trace dietary flavonol. Consumed at low levels in cloves and other plant foods with no signal of harm at those amounts.
• No toxicity in tested models. The isolated molecule inhibited sPLA2 without cellular toxicity in vitro ^{5Reference 5Novo Belchor M et al. · 2017In vitroEvaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2 — in vitroView study →}.
• Toxicology is under-characterised. No formal repeat-dose, genotoxicity or human-safety database exists for isolated rhamnetin ^{1Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →}.
• Flavonol-class interaction caveat. Like other flavonols it may inhibit drug-metabolising cytochrome-P450 enzymes and transporters in lab systems; interactions with narrow-margin medications are plausible but not clinically quantified.

No isolated-molecule reproductive or developmental-toxicity finding was identified in this pass. Any pregnancy or lactation decision belongs to the herb or product a person actually takes, not to this molecule-level page.

Dosage

There is no established human dose for isolated rhamnetin. Preclinical work spans low-micromolar cell-culture concentrations (the radiosensitization, cardiomyoblast, sPLA2 and hepatic studies) and rodent doses in the range of roughly 100–200 µg/kg up to a few mg/kg in the tumour-bearing-mouse antioxidant work ^{1,2,3Reference 1Medeiros DL et al. · 2022ReviewRhamnetin: a review of its pharmacology and toxicity — reviewView study →Reference 2Kang J et al. · 2013In vitroRhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (EMT) by miR-34a-mediated suppression of Notch-1 expression in non-small cell lung cancer cell lines — in vitro + xenograftView study →Reference 3Park ES et al. · 2014In vitroCardioprotective effects of rhamnetin in H9c2 cardiomyoblast cells under H₂O₂-induced apoptosis — in vitroView study →}. Because the compound occurs mostly as poorly-absorbed glycosides and is heavily conjugated after absorption, extrapolating any of these to a human dose is speculative. These are doses studied in research and are not a personal recommendation.

References

1. Medeiros DL, Lima ETG, Silva JC, Medeiros MA, Pinheiro EBF. (2022). Rhamnetin: a review of its pharmacology and toxicity — review. Journal of Pharmacy and Pharmacology, 74(6), 793–799. https://pubmed.ncbi.nlm.nih.gov/34931654/
2. Kang J, Kim E, Kim W, Seong KM, Youn H, Kim JW, Kim J, Youn B. (2013). Rhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (EMT) by miR-34a-mediated suppression of Notch-1 expression in non-small cell lung cancer cell lines — in vitro + xenograft. Journal of Biological Chemistry, 288(38), 27343–27357. https://pubmed.ncbi.nlm.nih.gov/23902763/
3. Park ES, Kang JC, Jang YC, Park JS, Jang SY, Kim DE, Kim B, Shin HS. (2014). Cardioprotective effects of rhamnetin in H9c2 cardiomyoblast cells under H₂O₂-induced apoptosis — in vitro. Journal of Ethnopharmacology, 153(3), 552–560. https://pubmed.ncbi.nlm.nih.gov/24607510/
4. Shatta MA, El-Derany MO, Gibriel AA, El-Mesallamy HO. (2023). Rhamnetin ameliorates non-alcoholic steatosis and hepatocellular carcinoma in vitro — in vitro. Molecular and Cellular Biochemistry, 478(11), 2439–2452. https://pubmed.ncbi.nlm.nih.gov/36495373/
5. Novo Belchor M, Hessel Gaeta H, Fabri Bittencourt Rodrigues C, Ramos da Cruz Costa C, de Oliveira Toyama D, Domingues Passero LF, Dalastra Laurenti M, et al. (2017). Evaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2 — in vitro. Molecules, 22(9), 1441. https://pubmed.ncbi.nlm.nih.gov/28858248/
6. Mattarei A, Biasutto L, Rastrelli F, Garbisa S, Marotta E, Zoratti M, Paradisi C. (2010). Regioselective O-derivatization of quercetin via ester intermediates. An improved synthesis of rhamnetin and development of a new mitochondriotropic derivative — synthesis. Molecules, 15(7), 4722–4736. https://pubmed.ncbi.nlm.nih.gov/20657388/

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