Agnuside

Agnuside at a Glance

Agnuside is an iridoid glucoside of chaste-tree fruit (Vitex agnus-castus), and one of the two compounds — alongside casticin — used as an HPLC standardisation marker for chaste-tree extracts.

That marker role is its main practical significance: it tells you a preparation contains what it claims, without being the compound responsible for the herb’s effects. Chaste tree’s clinical activity is dopaminergic and prolactin-lowering; agnuside’s own pharmacology is a thin but coherent preclinical anti-inflammatory record.

What It's Used For

Agnuside is an iridoid glucoside — p-hydroxybenzoyl aucubin ^{12Reference 12Kurüzüm-Uz A et al. · 2003Glucosides from Vitex agnus-castusView study →} — and, alongside casticin, one of the two HPLC standardization markers of chaste-tree fruit. The load-bearing distinction mirrors casticin’s: agnuside is a QC marker, and Vitex agnus-castus’s human PMS/mastalgia/prolactin evidence belongs to the herb’s dopaminergic diterpene extract, not to agnuside. Two things separate it from casticin, though: its own isolate signal is anti-inflammatory/anti-arthritic (not anticancer — in the one Vitex chemoprevention screen the active was vitetrifolin D, not agnuside ^{9Reference 9Li S et al. · 2013Compounds from Vitex agnus-castus fruits in chemoprevention via NQO1 induction (active = vitetrifolin D, not agnuside)View study →}), and it has no antimitotic mechanism. Its literature is thin but coherent, and entirely preclinical.

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. No human isolate data, so scores stay low by design.

01Anti-inflammatory / anti-arthriticShaky34%Three in-vivo models + COX-2 enzyme assay ^{1,2,3,4Reference 1Pandey A et al. · 2012Anti-arthritic activity of agnuside mediated through downregulation of inflammatory mediators and cytokinesView study →Reference 2Zhang L et al. · 2021Agnuside alleviates synovitis and fibrosis in knee osteoarthritis through inhibition of HIF-1α and the NLRP3 inflammasomeView study →Reference 3Tirpude NV et al. · 2022Agnuside mitigates OVA-LPS-induced perturbed lung homeostasis in allergic asthmaView study →Reference 4Suksamrarn A et al. · 2002Iridoids with anti-inflammatory activity from Vitex peduncularis (agnuside preferential COX-2 inhibition)View study →}

02AnalgesicShaky16%Inferred from the anti-arthritic/COX-2 endpoints ^{1,2,4Reference 1Pandey A et al. · 2012Anti-arthritic activity of agnuside mediated through downregulation of inflammatory mediators and cytokinesView study →Reference 2Zhang L et al. · 2021Agnuside alleviates synovitis and fibrosis in knee osteoarthritis through inhibition of HIF-1α and the NLRP3 inflammasomeView study →Reference 4Suksamrarn A et al. · 2002Iridoids with anti-inflammatory activity from Vitex peduncularis (agnuside preferential COX-2 inhibition)View study →}

03NeuroprotectiveShaky14%One AlCl₃ Alzheimer’s rodent study ^{7Reference 7Gnanarajan R et al. · 2025Agnuside enhances neuronal survival and cognitive function via PI3K/AKT/mTOR in AlCl₃-induced Alzheimer’s diseaseView study →}

04Metabolic / thermogenicShaky12%One NDUFAF6/mitochondrial study ^{8Reference 8Zhao Q et al. · 2026Agnuside stabilises the complex-I assembly factor NDUFAF6 to reinforce mitochondrial efficiency and thermogenic responsivenessView study →}

Mechanisms

Pharmacokinetics

Agnuside is a typical poorly-absorbed iridoid glucoside. The only isolate pharmacokinetic study (mice) reports absolute oral bioavailability ~0.7%, with greatest accumulation in the intestine ^{5Reference 5Ramakrishna R et al. · 2016AnimalPlasma pharmacokinetics, bioavailability and tissue distribution of agnuside in mice by LC-MS/MSView study →}; as an aucubin-type glucoside it is subject to intestinal β-glucosidase hydrolysis — agnuside is p-hydroxybenzoyl aucubin, so hydrolysis liberates aucubin plus p-hydroxybenzoic acid (the latter co-quantified in QC assays ^{13Reference 13Shah S et al. · 2013Validated HPLC method for p-hydroxybenzoic acid and agnuside in Vitex negundo and V. trifolia (QC marker)View study →}) — consistent with very low intact systemic exposure. It inhibits P-glycoprotein ATPase in vitro ^{11Reference 11Najar IA et al. · 2010Modulation of P-glycoprotein ATPase activity by some phytoconstituents (agnuside inhibitory)View study →}. Human data are limited to a single-volunteer plasma-assay demonstration (an analytical method paper, not an efficacy study) ^{6Reference 6Egeli D et al. · 2025Quantification of agnuside in human plasma with a novel HPLC method and a single-volunteer pharmacokinetic studyView study →}, and at herb-relevant intake (~0.09 mg/day marker quantity) systemic agnuside is negligible.

Clinical trials

There are no efficacy trials of the isolate. Agnuside has never been given to humans as a single compound therapeutically; the only human exposure on record is a single-volunteer plasma-assay demonstration ^{6Reference 6Egeli D et al. · 2025Quantification of agnuside in human plasma with a novel HPLC method and a single-volunteer pharmacokinetic studyView study →}. All human Vitex agnus-castus trials (PMS, mastalgia, cyclical breast pain, hyperprolactinemia, PCOS) tested the whole standardized fruit extract, with effects attributed to the dopaminergic diterpene fraction — agnuside serves only as an HPLC standardization marker there ^{14Reference 14Wuttke W et al. · 2003Chaste tree (Vitex agnus-castus) — pharmacology and clinical indicationsView study →}.

Last checked: July 2026.

Toxicity & Safety

Agnuside reads as a nontoxic iridoid glucoside, and at chaste-tree marker quantities the exposure is trivial anyway — the honest caveats are theoretical rather than observed harms.

Safety at a Glance

✅ Low / no toxicityDrug interactions

• Repeatedly characterized as nontoxic. No cytotoxicity against Vero cells, and no antimitotic mechanism of the kind casticin carries.
• Real-world exposure is tiny. As a chaste-tree standardization marker, incidental intake is roughly 0.09 mg/day.
• Avoid in pregnancy and breastfeeding. The caution comes from the source herb.
• Inhibits P-glycoprotein in vitro. A theoretical herb–drug interaction, untested in people.
• Pro-oxidant in one direct assay. Read its “antioxidant” label as a disease-model observation, not direct scavenging.

Full Safety & Interactions Detail

Agnuside is repeatedly characterized as a nontoxic iridoid glucoside — no cytotoxicity against Vero cells, oral efficacy at low doses (~6.25 mg/kg in rodents), and trivial human marker exposure (~0.09 mg/day) — supporting a low flag, and unlike casticin it has no antimitotic/tubulin mechanism and so no intrinsic cytotoxic-class concern. Two honest caveats keep the rating from being “none”: a pro-oxidant signal (enhanced Fe²⁺/ascorbate lipid peroxidation) in one direct assay ^{10Reference 10Najar IA et al. · 2016Effect of some phytoconstituents on Fe²⁺/ascorbate-induced lipid peroxidation (agnuside pro-oxidant)View study →}, so “antioxidant” should be read as an indirect disease-model observation rather than a direct scavenging property; and in-vitro P-glycoprotein inhibition ^{11Reference 11Najar IA et al. · 2010Modulation of P-glycoprotein ATPase activity by some phytoconstituents (agnuside inhibitory)View study →} implying a theoretical herb–drug-interaction potential.

Dosage

There is no established human dose — agnuside has never been given to humans as an isolate for therapy, and all dosing is preclinical (µM in vitro; ~6.25 mg/kg oral in rodents ^{2Reference 2Zhang L et al. · 2021Agnuside alleviates synovitis and fibrosis in knee osteoarthritis through inhibition of HIF-1α and the NLRP3 inflammasomeView study →}) that does not translate. As a chaste-tree constituent, incidental intake is ~0.09 mg/day from a standardized daily dose — a QC-marker quantity, not a therapeutic one.

References

1. Pandey A, et al. (2012). Anti-arthritic activity of agnuside mediated through downregulation of inflammatory mediators and cytokines. Inflammation Research. https://pubmed.ncbi.nlm.nih.gov/22228102/
2. Zhang L, et al. (2021). Agnuside alleviates synovitis and fibrosis in knee osteoarthritis through inhibition of HIF-1α and the NLRP3 inflammasome. Mediators of Inflammation. https://pubmed.ncbi.nlm.nih.gov/33814979/
3. Tirpude NV, et al. (2022). Agnuside mitigates OVA-LPS-induced perturbed lung homeostasis in allergic asthma. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/35144202/
4. Suksamrarn A, et al. (2002). Iridoids with anti-inflammatory activity from Vitex peduncularis (agnuside preferential COX-2 inhibition). Planta Medica. https://pubmed.ncbi.nlm.nih.gov/11842334/
5. Ramakrishna R, et al. (2016). Plasma pharmacokinetics, bioavailability and tissue distribution of agnuside in mice by LC-MS/MS. Journal of Pharmaceutical and Biomedical Analysis. https://pubmed.ncbi.nlm.nih.gov/27018507/
6. Egeli D, et al. (2025). Quantification of agnuside in human plasma with a novel HPLC method and a single-volunteer pharmacokinetic study. Journal of Chromatographic Science. https://pubmed.ncbi.nlm.nih.gov/39835650/
7. Gnanarajan R, et al. (2025). Agnuside enhances neuronal survival and cognitive function via PI3K/AKT/mTOR in AlCl₃-induced Alzheimer’s disease. Progress in Neuro-Psychopharmacology & Biological Psychiatry. https://pubmed.ncbi.nlm.nih.gov/41120087/
8. Zhao Q, et al. (2026). Agnuside stabilises the complex-I assembly factor NDUFAF6 to reinforce mitochondrial efficiency and thermogenic responsiveness. Advanced Science. https://pubmed.ncbi.nlm.nih.gov/42299748/
9. Li S, et al. (2013). Compounds from Vitex agnus-castus fruits in chemoprevention via NQO1 induction (active = vitetrifolin D, not agnuside). Evidence-Based Complementary and Alternative Medicine. https://pubmed.ncbi.nlm.nih.gov/23662135/
10. Najar IA, et al. (2016). Effect of some phytoconstituents on Fe²⁺/ascorbate-induced lipid peroxidation (agnuside pro-oxidant). Indian Journal of Experimental Biology. https://pubmed.ncbi.nlm.nih.gov/30183186/
11. Najar IA, et al. (2010). Modulation of P-glycoprotein ATPase activity by some phytoconstituents (agnuside inhibitory). Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/19653312/
12. Kurüzüm-Uz A, et al. (2003). Glucosides from Vitex agnus-castus. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/12895546/
13. Shah S, et al. (2013). Validated HPLC method for p-hydroxybenzoic acid and agnuside in Vitex negundo and V. trifolia (QC marker). Journal of Pharmaceutical Analysis. https://pubmed.ncbi.nlm.nih.gov/29403861/
14. Wuttke W, et al. (2003). Chaste tree (Vitex agnus-castus) — pharmacology and clinical indications. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/12809367/

View all 14 references▾