Agnuside

CAS Number	11027-63-7 (live-verified; independent registry confirmation)
Molecular Formula / MW	C22H26O11 / ~466.4 g/mol
Chemical Class	Iridoid glycoside — an aucubin-type iridoid esterified with p-hydroxybenzoic acid
Botanical Source	Vitex agnus-castus (chaste tree; chasteberry; monk’s pepper)
Plant Part(s)	Fruit (berry); also leaf
Typical Standardisation	Agnuside by HPLC; 0.5% commercial grade. Casticin is a co-marker
Claim Strength (Overview)	Moderate for chasteberry extract in PMS (multiple RCTs, meta-analysis); agnuside is a marker, not necessarily the sole active
Buy from Herbuno	Agnuside 0.5% Powder (Chasteberry Extract) | Standardized Vitex agnus-castus → Vitex Agnus Extract Powder →

Name origin: Agnuside is named for Vitex agnus-castus, and the plant’s epithet is itself a piece of pharmacological history: agnus castus means "chaste lamb," reflecting a long-held belief — recorded from Dioscorides through to medieval monasteries, where it earned the name "monk’s pepper" — that the berries suppressed libido. Structurally agnuside is an iridoid glycoside, an aucubin-type skeleton esterified with p-hydroxybenzoic acid. Traditional use: Chasteberry has an unusually consistent and specific traditional indication across two millennia of European practice: disorders of the female reproductive cycle. It appears in Greek, Roman, and medieval sources for menstrual complaints, and monastic use for the suppression of sexual desire persisted for centuries. The alignment of that traditional record with the modern clinical evidence base — premenstrual syndrome and hyperprolactinaemia — is notably tight. Research trajectory: German phytopharmaceutical research drove the modern evidence base, producing well-characterised commercial extracts (BNO 1095, Ze 440, and others) tested in properly designed randomized trials. The mechanistic account converged on dopaminergic activity: chasteberry constituents act as dopamine D2 receptor agonists, which suppresses prolactin secretion — a coherent endocrine explanation for a traditional gynaecological indication. Commercial source: Vitex agnus-castus fruit extract standardized to agnuside; note that the dopaminergic activity is attributed principally to diterpenes and flavonoids rather than to agnuside itself.

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Evidence for Agnuside Applications

The clinical evidence for chasteberry in premenstrual syndrome is among the better-supported in the botanical index, though it must be reported with its limitations. A systematic review of randomized controlled trials of Vitex extracts in women’s health identified thirteen RCTs and included twelve, of which eight investigated PMS, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia; for PMS, seven of eight trials found Vitex extracts superior to placebo, to pyridoxine, and to magnesium oxide, with adverse events mild and generally infrequent and methodological quality of the included studies generally moderate-to-high (van Die 2013). Seven of eight positive trials against multiple comparators is a substantive result. Claim strength: Moderate.

The counterweight is important and should not be omitted. A systematic review and meta-analysis of Vitex agnus castus preparations for PMS found that although meta-analysis shows a large pooled effect in placebo-controlled trials, the high risk of bias, high heterogeneity, and risk of publication bias among the included studies preclude a definitive conclusion, and the pooled treatment effects should be viewed as merely exploratory (Verkaik 2017). That is a considerably more cautious reading of the same literature, and a formulator should hold both: the effect is probably real, and the evidence base is not as clean as the headline pooled effect implies. Claim strength: Moderate.

The mechanistic account is coherent and endocrine rather than vaguely "hormone balancing." Chasteberry constituents act as dopamine D2 receptor agonists in the pituitary, and dopamine is the principal physiological inhibitor of prolactin release — so D2 agonism suppresses prolactin secretion. This explains the trial findings in latent hyperprolactinaemia, where one trial reported Vitex superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, and increasing mid-luteal progesterone and 17β-oestradiol, while another found it comparable to bromocriptine for reducing serum prolactin and easing cyclic mastalgia. Comparability to bromocriptine, a licensed dopamine agonist, is a strong mechanistic corroboration. Claim strength: Moderate.

Here is the uncomfortable point for a compound page: agnuside is a marker, and probably not the principal active. The dopaminergic activity driving the clinical effect is generally attributed to the diterpenes (notably clerodadienols) and to flavonoids such as casticin, not to agnuside, which is an iridoid glycoside without established D2 activity. Agnuside is standardised because it is abundant, chromatographically tractable, and reproducible — not because it was demonstrated to be the active. This is a common and rarely stated situation in botanical standardisation, and buyers should understand that an agnuside figure is a consistency marker rather than a potency measure. Claim strength: High (compositional fact).

Agnuside does have documented pharmacology in its own right, which is worth recording without overstating. It has been reported to show anti-arthritic activity, inhibiting vascular permeability and leukocyte migration in vivo, and to inhibit an array of pro-inflammatory mediators (PGE₂, LTB₄) and T-cell-mediated cytokines. It has also been reported to inhibit COX-2 with relative selectivity over COX-1, and to inhibit P-glycoprotein ATPase activity in a concentration-dependent manner — the latter being a theoretical interaction consideration rather than an established clinical one. Claim strength: Emerging.

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Dosage & Formulator Specification

Herbuno carries Vitex agnus-castus extract standardized to 0.5% agnuside by HPLC, alongside unstandardized Vitex agnus extract powder. Note that Herbuno also carries Vitex negundo (nirgundi) products — these are a different species with different chemistry and a different traditional indication, and must not be substituted into a chasteberry formulation.

Clinical trial dosing has used well-characterised proprietary extracts rather than raw agnuside, typically at extract doses in the range of 4–40 mg/day of dry extract (varying by extraction ratio) — one multi-centre placebo-controlled trial in China used BNO 1095 corresponding to 40 mg of herbal drug — taken once daily and continued through menses, with three months being a common trial duration and benefit typically emerging over cycles rather than days. Because agnuside is a consistency marker rather than the presumed active, formulators reproducing a trial result should match the extract specification and extraction ratio, not merely the agnuside percentage.

Analytical verification should specify agnuside by HPLC and, where the claim rests on the clinical literature, should additionally request casticin content, since the flavonoid and diterpene fractions carry the presumed dopaminergic activity. Extraction solvent and drug-to-extract ratio should be documented, as the well-studied commercial extracts are defined by their full manufacturing specification rather than by a single marker. Species authentication (V. agnus-castus, not V. negundo or V. trifolia) is essential and should be documented.

Chasteberry is well tolerated, with the systematic review finding adverse events mild and generally infrequent; gastrointestinal upset, headache, and acne are the most commonly reported. The cautions follow directly from the dopaminergic mechanism and are mechanistically specific rather than generic. Because it acts on dopamine D2 receptors, plausible interaction exists with dopamine agonists (e.g. bromocriptine, cabergoline) and with dopamine antagonists including antipsychotics, in either direction. Its effect on prolactin and the reproductive axis makes it inappropriate during pregnancy and breastfeeding (where prolactin suppression is actively undesirable), and caution is warranted alongside hormonal contraceptives and in hormone-sensitive conditions. Individuals with a prolactinoma or undiagnosed hyperprolactinaemia should be under medical care rather than self-treating.

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Frequently Asked Questions — Agnuside

Does chasteberry work for PMS?
Probably, though the evidence is less clean than headline claims suggest. A systematic review found seven of eight RCTs showed Vitex extracts superior to placebo, pyridoxine, and magnesium oxide. But a later meta-analysis, while finding a large pooled effect, noted that high risk of bias, high heterogeneity, and publication-bias risk preclude a definitive conclusion. Both readings are honest.

Is agnuside actually the active compound?
Probably not, and this is worth stating plainly. The dopaminergic activity driving the clinical effect is generally attributed to diterpenes and flavonoids such as casticin, not to agnuside. Agnuside is standardised because it is abundant and chromatographically tractable — it is a consistency marker rather than a potency measure.

How does chasteberry work?
Through dopamine. Its constituents act as dopamine D2 receptor agonists in the pituitary, and dopamine is the principal inhibitor of prolactin release — so D2 agonism suppresses prolactin. One trial found it comparable to bromocriptine, a licensed dopamine agonist, for reducing serum prolactin, which is strong mechanistic corroboration.

Are there interaction concerns?
Yes, and they follow directly from the mechanism. Because it acts at dopamine D2 receptors, plausible interaction exists with dopamine agonists (bromocriptine, cabergoline) and dopamine antagonists including antipsychotics. Its prolactin effect makes it inappropriate in pregnancy and breastfeeding, where prolactin suppression is actively undesirable.

Related compounds: Valerenic Acids, Kutkin, Vitexin, Apigenin

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Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.

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