# Vitex negundo Heteroins (Vitex negundo)

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**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-03
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** Vitex negundo L., Nirgundi, Five-leaved chaste tree, Huang Jing, Sambhalu, Lagundi

## Overview

Vitex negundo contains iridoid glycosides—chiefly agnuside—alongside flavonoids such as casticin, isoorientin, and scutellarin, which collectively exert antioxidant activity by scavenging [reactive oxygen species](/ingredients/condition/antioxidant), inhibiting lipid peroxidation, and modulating pro-inflammatory enzyme pathways. In preclinical models, standardized leaf extracts at 9.6–28.8 g/kg demonstrated [anti-inflammatory](/ingredients/condition/inflammation) efficacy comparable to methylprednisolone at 10 mg/kg in murine peritoneal inflammation assays, with agnuside showing docking scores exceeding 100 in binding studies against topoisomerase via 11 hydrogen bond interactions.

## Health Benefits

- **Antioxidant Protection**: Isoorientin, chlorogenic acid, and scutellarin in Vitex negundo leaf extracts neutralize free radicals and reduce oxidative stress markers by donating hydrogen atoms to [reactive oxygen species](/ingredients/condition/antioxidant), with phenolic content quantified at approximately 2.70 mg/g dried leaf weight providing measurable radical-scavenging capacity in DPPH assays.
- **[Anti-Inflammatory](/ingredients/condition/inflammation) Activity**: Agnuside and casticin suppress cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene synthesis; methanolic leaf extracts demonstrated significant chronic anti-inflammation in mouse peritoneal tissue models comparable to methylprednisolone at 10 mg/kg.
- **Antipyretic Effects**: Traditional Ayurvedic and Chinese medicine applications for fever management are supported by evidence that Vitex negundo leaf preparations reduce pyrogen-induced temperature elevations in animal models, likely through inhibition of prostaglandin E2 synthesis in the hypothalamus.
- **[Antimicrobial](/ingredients/condition/immune-support) Properties**: Viridiflorol, a sesquiterpenoid constituent, and phenolic compounds exhibit broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria, as well as anti-mycobacterium tuberculosis activity observed in in vitro callus extract studies.
- **Analgesic Activity**: The bitter and pungent leaf constituents, including iridoid glycosides and flavonoids, modulate pain signaling by inhibiting peripheral nociceptive pathways, with traditional use as a topical analgesic for rheumatic joints supported by preclinical writhing-test models.
- **Anthelmintic Action**: Leaf extracts demonstrate activity against intestinal helminths, attributed to the astringent tannins and alkaloids such as anhalonine that disrupt parasite neuromuscular function, consistent with centuries of documented use in Ayurveda for intestinal parasites.
- **Prolactin Modulation**: Phytochemicals in Vitex negundo, structurally related to those in Vitex agnus-castus, have been reported to reduce serum prolactin levels in hyperprolactinemia and mastodynia, plausibly through [dopamine](/ingredients/condition/mood)rgic receptor agonism in the anterior pituitary.

## Mechanism of Action

Agnuside, the principal iridoid glycoside, exerts antioxidant and anti-inflammatory effects partly through inhibition of topoisomerase enzymes, forming 11 hydrogen bonds with key amino acid residues at the active site, achieving docking scores exceeding 100 in computational binding studies, which may contribute to its anti-proliferative and cytoprotective actions. Flavonoids including isoorientin, casticin, and scutellarin donate phenolic hydroxyl groups to quench superoxide, hydroxyl, and peroxyl radicals, while simultaneously downregulating nuclear factor kappa-B (NF-κB) signaling to reduce transcription of [pro-inflammatory cytokine](/ingredients/condition/inflammation)s such as IL-1β, IL-6, and TNF-α. Chlorogenic acid inhibits glucose-6-phosphatase and modulates [lipid peroxidation](/ingredients/condition/antioxidant) via Nrf2/HO-1 pathway activation, adding a metabolic and cytoprotective dimension to the antioxidant profile. Viridiflorol contributes to anti-inflammatory effects by inhibiting 5-lipoxygenase activity, reducing leukotriene B4 synthesis, while the phytosterol fraction (quantified at approximately 1.1 mg/g leaf) may competitively inhibit arachidonic acid release from membrane phospholipids via phospholipase A2 modulation.

## Clinical Summary

No peer-reviewed randomized controlled trials specifically isolating Vitex negundo iridoid glycosides as a standardized supplement intervention in human subjects have been published with quantified effect sizes in the available literature. The most robust preclinical outcome is the [anti-inflammatory](/ingredients/condition/inflammation) equivalence to methylprednisolone at 10 mg/kg in murine models, though the administered leaf doses (9.6–28.8 g/kg) do not translate directly to practical human supplemental doses. Agnuside content in dried leaves has been quantified at 3.04 ± 0.02%, providing a basis for standardization, but human bioavailability, distribution, [metabolism](/ingredients/condition/weight-management), and excretion (ADME) data are lacking. Confidence in clinical benefit for humans remains low-to-moderate due to the exclusive reliance on animal and in vitro data; well-designed phase II clinical trials are needed before definitive efficacy claims can be substantiated.

## Nutritional Profile

Vitex negundo leaves are not consumed as a dietary staple but contain nutritionally relevant phytochemicals at quantified concentrations: phenolic compounds at approximately 2.70 mg/g dried weight, proteins at 2.49 mg/g, and phytosterols at 1.1 mg/g. The dominant fatty acid constituent identified by GC-MS in methanolic leaf extracts is octadecadienoic acid (linoleic acid derivative) at 21.93% of total extract composition in wild-sourced leaves, alongside hexadecanoic acid (palmitic acid). Iridoid glycoside agnuside is present at 3.04 ± 0.02% in dried leaves, representing the primary standardizable bioactive marker. Flavonoids including isoorientin, cynaroside (luteolin-7-glucoside), scutellarin, and casticin contribute to total polyphenol content, with chlorogenic acid adding hydroxycinnamic acid-class [antioxidant](/ingredients/condition/antioxidant)s; bioavailability of these compounds is expected to be influenced by the food matrix, intestinal glycosidase activity required to cleave glycoside bonds, and first-pass hepatic [metabolism](/ingredients/condition/weight-management) of aglycone forms.

## Dosage & Preparation

- **Traditional Leaf Decoction**: 5–10 g of dried Vitex negundo leaves boiled in 200 mL water for 15–20 minutes, strained and consumed twice daily in Ayurvedic practice for [anti-inflammatory](/ingredients/condition/inflammation) and antipyretic purposes.
- **Methanolic/Ethanolic Leaf Extract (Standardized to Agnuside)**: Extracts standardized to 3% agnuside are used in experimental contexts; no consensus human supplemental dose has been established from clinical trials.
- **Leaf Powder (Crude)**: Traditional Indian and Chinese preparations use 2–6 g of dried leaf powder mixed with honey or warm water; animal studies used 9.6–28.8 g/kg in mice, which does not directly translate to human dosing without allometric scaling.
- **Topical Paste**: Fresh leaves are crushed and applied externally to inflamed joints and skin conditions in traditional practice across South and Southeast Asia; no standardized topical formulation exists commercially.
- **Essential Oil (Aromatherapy/Topical)**: Leaf essential oil containing viridiflorol and other sesquiterpenoids is used in diluted form (1–3% in carrier oil) for topical anti-inflammatory and [antimicrobial](/ingredients/condition/immune-support) applications.
- **Timing Note**: Traditional preparations are typically administered after meals to reduce potential gastric irritation from bitter and astringent constituents; no clinical pharmacokinetic timing data are available.

## Safety & Drug Interactions

Vitex negundo preparations are generally regarded as low-toxicity in traditional use contexts, but rigorous human toxicology studies establishing no-observed-adverse-effect levels (NOAELs) or maximum tolerated doses in humans are absent from the published literature. The plant's reported ability to reduce serum prolactin levels through possible [dopamine](/ingredients/condition/mood)rgic activity raises a theoretical concern for interactions with dopamine antagonist medications such as antipsychotics (haloperidol, risperidone) and metoclopramide, potentially diminishing their therapeutic effect. Structural similarities of Vitex negundo phytochemicals to those in Vitex agnus-castus suggest potential hormonal interactions, making use during pregnancy and lactation inadvisable without medical supervision; the plant has historically been attributed emmenagogue and abortifacient properties in ethnobotanical records. Individuals on immunosuppressant therapy should exercise caution given the plant's documented [immunomodulatory](/ingredients/condition/immune-support) properties, and the bitter astringent constituents may exacerbate gastric irritation in individuals with peptic ulcer disease or acid reflux when taken in high oral doses.

## Scientific Research

The body of evidence for Vitex negundo bioactive compounds consists predominantly of in vitro cell-based assays and rodent animal studies, with no large-scale, placebo-controlled randomized human clinical trials (RCTs) identified as of the current literature review, placing this compound firmly in the preclinical evidence tier. Key animal studies include murine peritoneal inflammation models demonstrating [anti-inflammatory](/ingredients/condition/inflammation) efficacy of leaf extracts at 9.6 and 28.8 g/kg body weight equivalent to methylprednisolone 10 mg/kg, and in vitro DPPH and FRAP radical-scavenging assays confirming [antioxidant](/ingredients/condition/antioxidant) capacity correlated with phenolic content of 2.70 mg/g. Computational molecular docking analyses of agnuside against topoisomerase provide mechanistic hypotheses but do not substitute for pharmacokinetic or clinical outcome data. Phytochemical profiling studies of methanolic leaf extracts, identifying 24 bioactive compounds including octadecadienoic acid at 21.93% by GC-MS, are descriptive rather than interventional, and extrapolation to human supplemental doses requires significant caution.

## Historical & Cultural Context

Vitex negundo, known as 'Nirgundi' in Sanskrit Ayurvedic texts, has been documented in the Charaka Samhita and Sushruta Samhita—foundational texts of Ayurvedic medicine dating back over 2,000 years—as a primary remedy for rheumatic pain, nervous disorders, and inflammatory swellings, where leaf poultices and decoctions were applied both topically and internally. In traditional Chinese medicine, the plant is referred to as 'Huang Jing' or classified within the Mu Jing category, widely used in southern China for its [anti-inflammatory](/ingredients/condition/inflammation) and analgesic properties, and has been documented in the Chinese Pharmacopoeia as a medicinal resource for food, agriculture, and therapeutic applications. Across Southeast Asia, particularly in the Philippines and Indonesia, the aromatic leaves were burned as insect repellents and used as fumigants during fever management, while seeds and roots served as anthelmintics and abortifacients in ethnobotanical practice. The plant's bitter, pungent, and astringent organoleptic profile was interpreted through humoral medicine frameworks in both Ayurveda and Greek-influenced Unani medicine as indicative of 'cooling' and 'drying' properties suited to conditions of excess heat and inflammation.

## Synergistic Combinations

Vitex negundo iridoid glycosides and flavonoids may exhibit additive to synergistic [antioxidant](/ingredients/condition/antioxidant) effects when combined with other polyphenol-rich botanicals such as green tea extract (EGCG) or turmeric (curcumin), as these compounds act on complementary radical-scavenging pathways—Nrf2/HO-1 activation and NF-κB suppression—simultaneously. The [anti-inflammatory](/ingredients/condition/inflammation) profile of agnuside and casticin may be potentiated by boswellic acids from Boswellia serrata, which inhibit 5-lipoxygenase through a distinct binding site, creating dual-pathway inhibition of both COX and LOX arms of the arachidonic acid cascade. For prolactin-modulating applications, Vitex negundo is sometimes combined with Vitex agnus-castus in traditional compound formulations, though the pharmacodynamic interaction between their respective [dopamine](/ingredients/condition/mood)rgic constituents has not been formally studied in controlled settings.

## Frequently Asked Questions

### What are the main bioactive compounds in Vitex negundo?

Vitex negundo contains a diverse array of bioactive compounds including the iridoid glycoside agnuside (present at approximately 3.04% in dried leaves), flavonoids such as casticin, isoorientin, cynaroside, and scutellarin, phenolic acids including chlorogenic acid, sesquiterpenoids including viridiflorol, and fatty acids with octadecadienoic acid predominating at 21.93% of methanolic extract composition. The total phenolic content has been quantified at approximately 2.70 mg/g dried leaf weight, with phytosterols at 1.1 mg/g, collectively contributing to the plant's antioxidant and anti-inflammatory pharmacological profile.

### Is Vitex negundo safe to take during pregnancy?

Vitex negundo is not considered safe for use during pregnancy based on its ethnobotanical history of use as an emmenagogue and abortifacient in traditional medicine systems across South and Southeast Asia, suggesting uterotonic or hormonal activity. Additionally, its potential prolactin-lowering and dopaminergic activity raises further reproductive safety concerns, and no controlled human safety studies in pregnant populations have been conducted to establish safe exposure thresholds.

### How does Vitex negundo compare to Vitex agnus-castus (chasteberry)?

Vitex negundo and Vitex agnus-castus are closely related species within the Lamiaceae family sharing overlapping phytochemical profiles, including iridoid glycosides and flavonoids, and both have been associated with prolactin-reducing and anti-inflammatory effects, likely mediated through dopaminergic mechanisms in the anterior pituitary. However, Vitex agnus-castus has significantly more clinical trial data—including small RCTs in premenstrual syndrome and cyclical mastalgia—while Vitex negundo's evidence base remains largely preclinical, making direct efficacy comparisons premature.

### What is agnuside and what does it do?

Agnuside is an iridoid glycoside that serves as the primary standardizable bioactive marker in Vitex negundo, present at approximately 3.04 ± 0.02% in dried leaf material. In computational molecular docking studies, agnuside demonstrated exceptionally strong binding to topoisomerase enzymes via 11 hydrogen bonds with active site amino acid residues and docking scores exceeding 100, suggesting potential anti-proliferative and anti-inflammatory activity, though these findings require validation in human clinical pharmacokinetic and efficacy studies.

### What is the standard dosage of Vitex negundo extract?

No consensus standardized human supplemental dose for Vitex negundo extract has been established from controlled clinical trials; animal studies employed leaf equivalent doses of 9.6–28.8 g/kg body weight in mice, which do not translate directly to human doses without validated allometric scaling and bioavailability data. Traditional Ayurvedic practice uses 5–10 g of dried leaves as a decoction or 2–6 g of leaf powder per day, while commercial extracts are sometimes standardized to 3% agnuside content, though optimal human dosing requires formal pharmacokinetic investigation before evidence-based recommendations can be made.

### What is the antioxidant strength of Vitex negundo compared to other herbal extracts?

Vitex negundo leaf extracts demonstrate measurable antioxidant capacity with phenolic content quantified at approximately 2.70 mg/g dried leaf weight, which shows free radical-scavenging activity in DPPH assays. The bioactive compounds isoorientin, chlorogenic acid, and scutellarin work synergistically to neutralize reactive oxygen species by donating hydrogen atoms. While direct head-to-head comparisons with other herbal extracts are limited, this phenolic concentration places Vitex negundo in a moderate range among medicinal plants used for oxidative stress support.

### How does Vitex negundo absorption change when taken with food versus on an empty stomach?

Vitex negundo's phenolic compounds and flavonoids may have improved absorption when consumed with meals containing dietary fats, as many plant polyphenols are fat-soluble. However, specific bioavailability studies comparing fed versus fasted states for Vitex negundo extract have not been extensively published in clinical literature. Taking the extract consistently at the same time daily—with or without food—is more important than the timing relative to meals for maintaining steady-state levels.

### Does Vitex negundo have anti-inflammatory effects beyond hormonal balance?

Vitex negundo contains multiple anti-inflammatory compounds that may reduce systemic inflammation markers independently of hormonal pathways, though research specifically isolating these non-hormonal mechanisms remains limited. The phenolic and flavonoid content suggests potential benefits for general inflammatory conditions, but most clinical evidence focuses on its traditional use for reproductive and menstrual health. Additional research is needed to establish whether Vitex negundo should be considered a standalone anti-inflammatory agent or if benefits are primarily linked to hormone regulation.

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