Isoquercitrin

Pharmacology & Research

Isoquercitrin is quercetin carrying a single glucose at its 3-O position (quercetin-3-O-glucoside) — the glucoside sibling of rutin (the 3-O-rutinoside) and hyperoside (the 3-O-galactoside), and a stored, sugar-capped form of the flavonol quercetin ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →}. Across this database it appears as a co-occurring antioxidant flavonoid — it is the principal flavonoid and pharmacopoeial marker of horsetail (the European Pharmacopoeia expresses total flavonoids “as isoquercitrin”, minimum 0.3%) ^{13Reference 13Mimica-Dukić N et al. · 2008In vitroPhenolic compounds in field horsetail (Equisetum arvense L.) as natural antioxidants — in vitro (isoquercitrin as marker)View study →}, part of the aquaretic-diuretic flavonoid fraction of goldenrod ^{15Reference 15Chodera A et al. · 1991AnimalEffect of flavonoid fractions of Solidago virgaurea L. on diuresis and levels of electrolytes — rat in vivo animal modelView study →}, and one of the quercetin glycosides in bearberry leaf (~2.7–5.7 mg/g as quercetin glucoside) ^{14Reference 14Song XC et al. · 2021Discovery and characterization of phenolic compounds in bearberry (Arctostaphylos uva-ursi) leaves using liquid chromatography-ion mobility-high-resolution mass spectrometry — analytical (concentration)View study →}, stevia leaf and houttuynia. What makes isoquercitrin worth separating from its siblings is bioavailability: the 3-O-glucoside is the one quercetin glycoside cleaved at the small-intestinal brush border (by lactase-phlorizin hydrolase) rather than needing colonic bacteria, so quercetin from it appears in blood early and more completely than from rutin or hyperoside ^{4Reference 4Sesink AL et al. · 2003AnimalIntestinal uptake of quercetin-3-glucoside in rats involves hydrolysis by lactase phlorizin hydrolase — rat in situView study →5Reference 5Day AJ et al. · 2003AnimalAbsorption of quercetin-3-glucoside and quercetin-4′-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter — rat in situView study →}. That relative advantage is why the isolated molecule — as plain “isoquercetin” — has actually reached human trials, an unusual position for a plant flavonoid.

1. Antithrombotic & thromboinflammation (PDI)

The strongest and most distinctive line, and the reason isoquercitrin has a human file at all. Quercetin flavonoids inhibit extracellular protein disulfide isomerase (PDI) — an enzyme released by activated platelets and endothelium that is required for thrombus formation — and isoquercetin was chosen for the human program because it is better absorbed than rutin, the molecule that first flagged the mechanism ^{7Reference 7Zwicker JI et al. · 2019Clinical trialTargeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer — phase-II clinical trialView study →}. A human proof-of-mechanism study showed PDI inhibition blocks thrombin generation by interfering with platelet factor-V activation ^{6Reference 6Stopa JD et al. · 2017Protein disulfide isomerase inhibition blocks thrombin generation in humans by interfering with platelet factor V activation — human proof-of-mechanismView study →}. In the phase-II CATIQ trial in advanced-cancer patients, plain isoquercetin at 1,000 mg/day for 56 days cut plasma D-dimer by ~22%, platelet-dependent thrombin generation by ~57% and soluble P-selectin by ~58%, with no VTE events or major bleeds ^{7Reference 7Zwicker JI et al. · 2019Clinical trialTargeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer — phase-II clinical trialView study →}. An independent phase-II trial in sickle-cell disease (1,000 mg/day for 28 days) likewise reduced whole-blood coagulation, collagen-induced platelet aggregation, monocyte tissue-factor expression and plasma PDI reductase activity, again with no off-target bleeding ^{8Reference 8Lizarralde-Iragorri MA et al. · 2024RCTIsoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial — phase-II clinical trialView study →}.

Gap: both trials are small, biomarker-endpoint phase-II studies — they establish target engagement and safety, not a proven reduction in clinical thrombosis; and the agent is plain isoquercetin, so the read-through to dietary isoquercitrin exposure is limited.

2. Allergic rhinitis & anti-allergic

The one other human signal — but read the form carefully. In a randomised, double-blind, placebo-controlled trial in Japanese-cedar pollinosis, enzymatically-modified isoquercitrin (EMIQ) — a semi-synthetic, glucose-chain-extended derivative engineered for better solubility and absorption — at 100 mg/day for 8 weeks significantly reduced total ocular and ocular-itching scores versus placebo ^{9Reference 9Kawai M et al. · 2009RCTEffect of enzymatically modified isoquercitrin, a flavonoid, on symptoms of Japanese cedar pollinosis: a randomized double-blind placebo-controlled trial — clinical trial (EMIQ)View study →}. The anti-allergic rationale is quercetin-class mast-cell / histamine-release inhibition, delivered by a better-absorbed glycoside ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →3Reference 3Owczarek-Januszkiewicz A et al. · 2022ReviewEnzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms — reviewView study →}.

Gap: the tested molecule is EMIQ, not plain isoquercitrin — its improved pharmacokinetics are exactly the point, so the result cannot be transferred to native isoquercitrin at face value; and the benefit was on ocular, not the full symptom, endpoints ^{3Reference 3Owczarek-Januszkiewicz A et al. · 2022ReviewEnzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms — reviewView study →9Reference 9Kawai M et al. · 2009RCTEffect of enzymatically modified isoquercitrin, a flavonoid, on symptoms of Japanese cedar pollinosis: a randomized double-blind placebo-controlled trial — clinical trial (EMIQ)View study →}.

3. Antioxidant & organ protection

Isolated isoquercitrin is cytoprotective against oxidative injury, with two reasonably resolved mechanisms. In a mouse intestinal ischaemia-reperfusion model, isoquercitrin limited injury by remodelling gut flora and inhibiting NLRP3-inflammasome activation (lower caspase-1, IL-1β, IL-6) ^{10Reference 10Xu H et al. · 2025AnimalIsoquercitrin mitigates intestinal ischemia-reperfusion injury by regulating intestinal flora and inhibiting NLRP3 inflammasome activation — mouse in vivo animal modelView study →}. In human endothelial (EA.hy926) cells, it protected against hydrogen-peroxide-induced apoptosis via the PI3K/Akt/GSK3β survival axis ^{11Reference 11Zhu M et al. · 2016In vitroIsoquercitrin inhibits hydrogen peroxide-induced apoptosis of EA.hy926 cells via the PI3K/Akt/GSK3β signaling pathway — in vitroView study →}. Reviews add antioxidant activity through direct radical scavenging and Nrf2/HO-1 induction across many models ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →} — the same antioxidant capacity that makes it horsetail’s flavonoid marker ^{13Reference 13Mimica-Dukić N et al. · 2008In vitroPhenolic compounds in field horsetail (Equisetum arvense L.) as natural antioxidants — in vitro (isoquercitrin as marker)View study →}.

Gap: all cell and rodent work; the in-vivo relevance of the concentrations used is limited by the fact that isoquercitrin is hydrolysed to quercetin before absorption, so systemic exposure is to quercetin metabolites, not the intact glucoside ^{4Reference 4Sesink AL et al. · 2003AnimalIntestinal uptake of quercetin-3-glucoside in rats involves hydrolysis by lactase phlorizin hydrolase — rat in situView study →5Reference 5Day AJ et al. · 2003AnimalAbsorption of quercetin-3-glucoside and quercetin-4′-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter — rat in situView study →}.

4. Metabolic & antidiabetic

Isolated isoquercitrin shows antidiabetic activity across preclinical models — inhibition of carbohydrate-handling and polyol-pathway enzymes (α-glucosidase, aldose reductase), improved glucose handling and antioxidant protection of pancreatic and vascular tissue — collated in the pharmacology reviews ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →2Reference 2Orfali GC et al. · 2016ReviewReview of anticancer mechanisms of isoquercitin — reviewView study →}. Within the database this fits its presence in the antioxidant leaf-flavonoid fraction of stevia and the flavonoid fraction of goldenrod ^{15Reference 15Chodera A et al. · 1991AnimalEffect of flavonoid fractions of Solidago virgaurea L. on diuresis and levels of electrolytes — rat in vivo animal modelView study →}.

Gap: entirely cell and animal data at concentrations the poor oral bioavailability makes hard to reach systemically; there is no isolated-isoquercitrin human metabolic trial, and any effect is confounded with quercetin’s ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →4Reference 4Sesink AL et al. · 2003AnimalIntestinal uptake of quercetin-3-glucoside in rats involves hydrolysis by lactase phlorizin hydrolase — rat in situView study →}.

5. Antiviral & anti-inflammatory

The broadest but thinnest tier. Isoquercitrin is one of four principal leaf flavonoids from houttuynia shown to attenuate H1N1-influenza-induced pneumonia in mice, with gut-bacterial biotransformation shaping the active species ^{12Reference 12Tang J et al. · 2023AnimalTherapeutic effects on H1N1-induced pneumonia in mice and intestinal bacteria biotransformation of four main flavonoids from Houttuynia cordata Thunb. — mouse in vivo animal modelView study →}, and reviews catalogue antiviral (including flaviviral) and general anti-inflammatory activity for the isolated molecule across cultured systems ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →2Reference 2Orfali GC et al. · 2016ReviewReview of anticancer mechanisms of isoquercitin — reviewView study →}.

Gap: most of this is in-vitro or mixed-flavonoid animal work at high concentrations; the influenza study tested four flavonoids together rather than isoquercitrin alone, and there are no human antiviral or anti-inflammatory data for the isolated molecule ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →12Reference 12Tang J et al. · 2023AnimalTherapeutic effects on H1N1-induced pneumonia in mice and intestinal bacteria biotransformation of four main flavonoids from Houttuynia cordata Thunb. — mouse in vivo animal modelView study →}.

Mechanisms

Target / pathway	Effect	Relevant to
Protein disulfide isomerase (PDI)	Inhibits → ↓platelet-dependent thrombin generation & thrombosis	Antithrombotic / thromboinflammation
Mast-cell histamine release	Inhibits → ↓allergic response	Allergic rhinitis (as EMIQ)
Nrf2 / HO-1	Induces → ↑antioxidant defence	Antioxidant / organ protection
NLRP3 inflammasome (caspase-1, IL-1β)	Suppresses → ↓inflammatory injury	Intestinal IR, general anti-inflammatory
PI3K/Akt/GSK3β	Activates → pro-survival, anti-apoptotic	Endothelial / cytoprotection
α-glucosidase, aldose reductase	Inhibits → ↓glucose load, polyol-pathway flux	Metabolic / antidiabetic
Hydrolysis → quercetin (brush-border LPH)	Glucose removed by lactase-phlorizin hydrolase → quercetin absorbed	Governs all systemic effects

Pharmacokinetics

Bioavailability is the load-bearing caveat, but here it also carries the good news that sets isoquercitrin apart from its siblings. Like rutin and hyperoside, isoquercitrin is a glycoside that is not absorbed intact — the sugar must come off first and quercetin is what enters the blood. But the 3-O-glucoside is uniquely well-placed to be cleaved early: it is a substrate for lactase-phlorizin hydrolase (LPH), the brush-border β-glucosidase on the luminal surface of the small intestine, so it is hydrolysed and its quercetin absorbed in the upper gut — hours before rutin, whose rutinose cap resists small-intestinal enzymes and forces colonic bacterial activation ^{4Reference 4Sesink AL et al. · 2003AnimalIntestinal uptake of quercetin-3-glucoside in rats involves hydrolysis by lactase phlorizin hydrolase — rat in situView study →5Reference 5Day AJ et al. · 2003AnimalAbsorption of quercetin-3-glucoside and quercetin-4′-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter — rat in situView study →}. Consequently quercetin from isoquercitrin appears in plasma faster and more completely than from rutin, and isoquercitrin is roughly four-fold more water-soluble than quercetin itself ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →}. Even so, absolute oral bioavailability is still modest, which is why the commercial enzymatically-modified isoquercitrin (EMIQ) — with extra glucose units added to further boost solubility and absorption — was developed as the better-delivered form ^{3Reference 3Owczarek-Januszkiewicz A et al. · 2022ReviewEnzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms — reviewView study →}. The practical upshot: isoquercitrin is the best-delivered of the common quercetin glycosides, but the circulating species is quercetin and its conjugates, so its systemic pharmacology cannot be cleanly separated from quercetin’s ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →4Reference 4Sesink AL et al. · 2003AnimalIntestinal uptake of quercetin-3-glucoside in rats involves hydrolysis by lactase phlorizin hydrolase — rat in situView study →5Reference 5Day AJ et al. · 2003AnimalAbsorption of quercetin-3-glucoside and quercetin-4′-glucoside in the rat small intestine: the role of lactase phlorizin hydrolase and the sodium-dependent glucose transporter — rat in situView study →}.

Clinical trials

Isoquercitrin is unusual among plant flavonoids in having isolated-molecule human trials — but they split by form. Plain isoquercetin has two completed phase-II trials on thrombosis biomarkers (advanced cancer, sickle-cell disease) ^{7Reference 7Zwicker JI et al. · 2019Clinical trialTargeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer — phase-II clinical trialView study →8Reference 8Lizarralde-Iragorri MA et al. · 2024RCTIsoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial — phase-II clinical trialView study →}; the EMIQ derivative has a completed allergic-rhinitis RCT ^{9Reference 9Kawai M et al. · 2009RCTEffect of enzymatically modified isoquercitrin, a flavonoid, on symptoms of Japanese cedar pollinosis: a randomized double-blind placebo-controlled trial — clinical trial (EMIQ)View study →}. All are small, surrogate-endpoint studies. Everything else on this page is preclinical.

Completed (plain isoquercetin)	Completed (EMIQ)	Endpoints	Preclinical
2 phase-II (cancer, sickle cell)	1 RCT (pollinosis)	Biomarker / symptom (no hard-outcome trial)	Extensive

Last checked: July 2026.

Toxicity & Safety

Isoquercitrin carries a low toxicity flag: it is a common dietary quercetin glycoside with a long history of incidental exposure, and the dedicated pharmacology/toxicology review describes it as well tolerated with low toxicity across animal studies ^{1Reference 1Valentová K et al. · 2014ReviewIsoquercitrin: pharmacology, toxicology, and metabolism — reviewView study →}. Its human trial record, though small, is reassuring on safety — the cancer and sickle-cell isoquercetin trials at 1,000 mg/day reported no major haemorrhage or off-target bleeding despite the antithrombotic mechanism ^{7Reference 7Zwicker JI et al. · 2019Clinical trialTargeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer — phase-II clinical trialView study →8Reference 8Lizarralde-Iragorri MA et al. · 2024RCTIsoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial — phase-II clinical trialView study →}, and the EMIQ pollinosis trial reported no significant adverse effects ^{9Reference 9Kawai M et al. · 2009RCTEffect of enzymatically modified isoquercitrin, a flavonoid, on symptoms of Japanese cedar pollinosis: a randomized double-blind placebo-controlled trial — clinical trial (EMIQ)View study →}. The EMIQ derivative has additionally been through formal safety and genotoxicity evaluation supporting its food use ^{3Reference 3Owczarek-Januszkiewicz A et al. · 2022ReviewEnzymatically Modified Isoquercitrin: Production, Metabolism, Bioavailability, Toxicity, Pharmacology, and Related Molecular Mechanisms — reviewView study →}. The most relevant caution is mechanistic and inherited from quercetin: because isoquercitrin is hydrolysed to quercetin before absorption, quercetin’s interaction profile applies downstream — quercetin inhibits CYP3A4 and P-glycoprotein and can disturb narrow-margin substrates, and quercetin/isoquercetin’s PDI-inhibiting, antiplatelet activity is a reasonable (mechanism-based) caution alongside anticoagulant or antiplatelet drugs, though the isoquercetin trials found no excess bleeding. Dedicated human drug-interaction data for isolated isoquercitrin do not exist.

Dosage

There is no established general dose of isoquercitrin. The human antithrombotic trials used plain isoquercetin at 500–1,000 mg/day (effects clearest at 1,000 mg/day) for 4–8 weeks ^{7Reference 7Zwicker JI et al. · 2019Clinical trialTargeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer — phase-II clinical trialView study →8Reference 8Lizarralde-Iragorri MA et al. · 2024RCTIsoquercetin for thromboinflammation in sickle cell disease: a randomized double-blind placebo-controlled trial — phase-II clinical trialView study →}; the allergic-rhinitis RCT used EMIQ at 100 mg/day for 8 weeks — a different, better-absorbed molecule, so its dose does not transfer to native isoquercitrin ^{9Reference 9Kawai M et al. · 2009RCTEffect of enzymatically modified isoquercitrin, a flavonoid, on symptoms of Japanese cedar pollinosis: a randomized double-blind placebo-controlled trial — clinical trial (EMIQ)View study →}. Preclinical work uses higher milligram-per-kilogram oral doses in rodents and high-micromolar concentrations in cell culture, figures inflated to offset the pre-absorption hydrolysis to quercetin.

These are doses studied in research and are not a personal recommendation. Anyone on anticoagulant or antiplatelet drugs should seek professional guidance.

References