# Vitexnegheteroin (Vitex negundo L.)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/vitexnegheteroin-vitex-negundo-l
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-05
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** Vitex negundo L., Nirgundi, Five-leaved Chaste Tree, Huang Jing Zi, Sambhalu, Lagundi

## Overview

Vitex negundo leaf extracts contain iridoid glycosides (notably agnuside at 3.04 ± 0.02% dry weight), flavonoids (isoorientin, isovitexin, scutellarin), and terpenoids (viridiflorol) that exert antioxidant activity via [free radical scaveng](/ingredients/condition/antioxidant)ing and hydrogen bond-mediated enzyme inhibition. Preclinical murine models demonstrate significant [anti-inflammatory](/ingredients/condition/inflammation) efficacy at 9.6–28.8 g/kg leaf weight equivalents, with outcomes comparable to methylprednisolone (10 mg/kg), though no controlled human clinical trials have yet confirmed these effects.

## Health Benefits

- **Antioxidant Activity**: Flavonoids including isoorientin, isovitexin, and scutellarin scavenge [reactive oxygen species](/ingredients/condition/antioxidant) (ROS) through electron donation; quantified antioxidant fractions show dose-dependent radical quenching in LC-ECD assays calibrated at 0.25–50 µg/mL (R²=0.9993).
- **[Anti-inflammatory](/ingredients/condition/inflammation) Effects**: Methanolic leaf extracts at 9.6 g/kg and 28.8 g/kg (mouse body weight) significantly reduced chronic peritoneal inflammation to levels comparable to the corticosteroid methylprednisolone (10 mg/kg), suggesting potent prostaglandin or cytokine pathway modulation.
- **Analgesic Properties**: Traditional Ayurvedic use and preclinical data support pain-relieving effects attributed to agnuside and terpenoid constituents, likely through inhibition of COX-mediated nociceptive pathways, though specific IC50 values for pain endpoints in mammalian models are not yet fully characterized.
- **Prolactin-Lowering (Hyperprolactinemia Relief)**: Octadecadienoic acid and terpenoids within V. negundo extracts have been associated with serum prolactin reduction, offering a mechanistic basis for their traditional use in mastodynia (breast pain) and menstrual irregularities linked to elevated prolactin.
- **[Antimicrobial](/ingredients/condition/immune-support) Activity**: GC-MS-identified constituents including hexadecanoic acid methyl ester and viridiflorol demonstrate inhibitory activity against Mycobacterium tuberculosis and other pathogens, positioning the plant as a candidate adjunct in infectious disease research.
- **Anti-tumor Potential**: Phenolic acids (2.70 mg/g dried extract) and phytosterols (1.1 mg/g) contribute to cytostatic and pro-apoptotic effects observed in cell-line studies, attributed to disruption of redox homeostasis in rapidly proliferating cells.
- **Antipyretic and Anthelmintic Effects**: Bitter and pungent leaf constituents including oleanolic acid, sitosterol, negundoside, and vetugnoside have been documented in Ayurvedic texts and corroborated by preclinical data as contributing to fever reduction and intestinal parasite clearance.

## Mechanism of Action

Agnuside, the principal iridoid glucoside quantified at 3.04 ± 0.02% in dried V. negundo leaves, exhibits strong antioxidant and anti-inflammatory activity via formation of up to 11 hydrogen bonds with topoisomerase enzyme residues alongside Amide-Pi Stacked and Pi-Alkyl interactions (in silico docking scores >100), effectively competing with endogenous substrates at catalytic sites. Flavonoids such as isoorientin and scutellarin donate hydrogen atoms to neutralize peroxyl and hydroxyl radicals, reducing [lipid peroxidation](/ingredients/condition/antioxidant) cascades and attenuating NF-κB-dependent [pro-inflammatory cytokine](/ingredients/condition/inflammation) transcription. Octadecadienoic acid (a polyunsaturated fatty acid comprising 21.93% of wild-leaf GC-MS fractions) and the sesquiterpenoid viridiflorol modulate arachidonic acid [metabolism](/ingredients/condition/weight-management), reducing downstream prostaglandin E2 synthesis and suppressing serum prolactin through [dopamine](/ingredients/condition/mood)rgic receptor pathway interactions. Phenolic acids and phytosterols (sitosterol, oleanolic acid) contribute additional membrane-stabilizing and enzyme-inhibitory effects that collectively account for the broad-spectrum pharmacological activity observed in preclinical models.

## Clinical Summary

No registered human clinical trials with defined endpoints, sample sizes, or statistically reported effect sizes have been published for Vitex negundo extracts or its isolated compounds (agnuside, isoorientin, octadecadienoic acid) as of available literature. Animal model data in mice provide a preliminary signal for [anti-inflammatory](/ingredients/condition/inflammation) efficacy comparable to corticosteroid reference drugs at high oral doses (9.6–28.8 g/kg), but allometric scaling to human equivalents yields dose estimates that require formal safety and pharmacokinetic characterization before clinical use. Traditional use across centuries in Ayurveda and TCM for fever, pain, mastodynia, and inflammation represents ethnopharmacological evidence of efficacy, though this does not substitute for controlled clinical outcome data. Confidence in translational benefit remains low-to-moderate pending well-designed phase I dose-escalation and phase II efficacy trials in human populations.

## Nutritional Profile

Vitex negundo leaves contain a complex phytochemical matrix rather than a conventional macronutrient profile. Key constituents include phenolic acids at approximately 2.70 mg/g dried leaf, phytosterols (primarily sitosterol and oleanolic acid) at 1.1 mg/g, and total lipids at approximately 0.5% w/w dominated by octadecadienoic acid (linoleic acid, 21.93% of GC-MS fraction in wild leaf). Iridoid glycosides including agnuside are present at 3.04 ± 0.02% by HPLC dry weight, representing the principal standardizable marker compound. Flavonoids—isoorientin, isovitexin, scutellarin, cynaroside, and chlorogenic acid—contribute to total polyphenol content, though aggregate polyphenol quantification across standardized extraction methods has not been uniformly reported. Bioavailability of agnuside and flavonoid glycosides is expected to be influenced by intestinal glucosidase activity and first-pass hepatic [metabolism](/ingredients/condition/weight-management), with aglycone forms likely exhibiting greater membrane permeability, though formal human pharmacokinetic data are absent.

## Dosage & Preparation

- **Traditional Aqueous/Methanolic Leaf Extract**: Prepared by cold maceration or Soxhlet extraction of dried leaves in 70–100% methanol; used experimentally at 9.6–28.8 g/kg in mice (human equivalent dose not established).
- **Dried Leaf Powder**: Traditionally consumed at 3–6 g/day in Ayurvedic formulations, though no pharmacopoeial standardization exists for V. negundo leaf powder in Western regulatory frameworks.
- **Standardized Agnuside Extract**: Research-grade HPLC-standardized extracts contain 3.04 ± 0.02% agnuside by dry weight; no commercial supplement standardization has been formally established.
- **Decoction (Traditional TCM/Ayurveda)**: Leaves boiled in water (10–20 g dried leaf per 500 mL) for 15–20 minutes; filtered and consumed as a tea for analgesic and antipyretic effects.
- **Callus-Derived Concentrate (Experimental)**: In vitro callus cultures on Murashige-Skoog (MS) medium with 2.0 mg/L BAP and 0.2 mg/L 2,4-D yield extracts with up to 47.79% octadecadienoic acid; not available commercially.
- **Topical Leaf Paste**: Fresh leaves ground and applied directly to joints or inflamed areas in traditional practice; no standardized formulation or validated clinical dose exists.
- **Timing Note**: [Anti-inflammatory](/ingredients/condition/inflammation) and [antioxidant](/ingredients/condition/antioxidant) effects in preclinical models are assessed after repeated dosing over days to weeks; single-dose kinetics in humans are unknown.

## Safety & Drug Interactions

Formal human safety data for Vitex negundo extracts are not available, as no phase I clinical trials have been published; preclinical murine studies at doses up to 28.8 g/kg leaf weight equivalent did not report acute toxicity, suggesting a broad safety margin in animal models, but this cannot be directly extrapolated to humans. The prolactin-lowering activity attributed to [dopamine](/ingredients/condition/mood)rgic constituents raises a theoretical concern for interaction with dopamine antagonist medications (e.g., antipsychotics such as haloperidol, metoclopramide) and hormone-sensitive conditions. Pregnancy and lactation use is contraindicated based on traditional advisory caution and the plant's documented hormonal (prolactin-lowering) and uterine-stimulating properties noted in ethnomedicinal texts; no controlled reproductive toxicity studies have been conducted. Individuals with hypersensitivity to Lamiaceae (mint family) plants should exercise caution, and concurrent use with immunosuppressants or [anti-inflammatory](/ingredients/condition/inflammation) medications warrants medical supervision given the potential for pharmacodynamic additive effects.

## Scientific Research

The existing evidence base for Vitex negundo is almost entirely preclinical, comprising in vitro assays and rodent (murine) models, with no published randomized controlled human clinical trials identified in the peer-reviewed literature to date. Key preclinical findings include significant chronic [anti-inflammatory](/ingredients/condition/inflammation) activity in mouse peritoneal models at oral doses of 9.6 g/kg and 28.8 g/kg leaf equivalents, benchmarked against methylprednisolone (10 mg/kg), and quantitative phytochemical profiling via validated HPLC (R²=0.9999, RSD ≤2.50%) and GC-MS methods identifying 24 bioactive compounds. In vitro callus induction studies demonstrated that white and green callus cultures produce 40.38% and 47.79% octadecadienoic acid respectively—nearly double the 21.93% found in wild leaves—suggesting biotechnological strategies for producing concentrated bioactive material. The overall evidence quality is limited (evidence score 4/10), and extrapolation of preclinical dose–response data to human therapeutic windows requires significant caution and formal phase I/II clinical investigation.

## Historical & Cultural Context

Vitex negundo has been documented in Ayurvedic texts including the Charaka Samhita and Sushruta Samhita under the Sanskrit name 'Nirgundi,' where it is classified as a bitter, pungent, and astringent herb with hot potency (Ushna Veerya) prescribed for fever, rheumatic pain, elephantiasis, and worm infestations. In Traditional Chinese Medicine, it is referenced as 'Huang Jing Zi' and used for wind-damp painful obstruction, headache, and eye disorders. Across Southeast Asia, leaves are traditionally smoked or used as fumigants against insects, and fresh leaf poultices are applied to arthritic joints, bruises, and sprains in folk medicine from the Philippines, Sri Lanka, and Indonesia. Colonial-era botanical surveys by British naturalists in India (18th–19th centuries) documented its widespread medicinal use, and it remains an officially recognized plant in the Ayurvedic Pharmacopoeia of India.

## Synergistic Combinations

Vitex negundo extracts may exhibit additive or synergistic [antioxidant](/ingredients/condition/antioxidant) effects when combined with Withania somnifera (ashwagandha), as withanolides complement iridoid glycoside-mediated NF-κB suppression through independent MAPK pathway modulation, potentially broadening the [anti-inflammatory](/ingredients/condition/inflammation) coverage. Co-administration with curcumin (from Curcuma longa) is theoretically synergistic given complementary COX-2 inhibition by curcuminoids and prostaglandin pathway modulation by V. negundo terpenoids, a pairing commonly employed in Ayurvedic compound formulations (Rasayanas). The flavonoid fraction of V. negundo (isoorientin, scutellarin) may also potentiate the bioavailability of lipophilic phytosterols such as sitosterol through mixed micellar formation in the gastrointestinal tract, though this mechanism has not been formally validated for this specific plant.

## Frequently Asked Questions

### What is the main active compound in Vitex negundo and what does it do?

The principal standardizable bioactive compound in Vitex negundo is agnuside, an iridoid glucoside quantified at 3.04 ± 0.02% in dried leaves by validated HPLC. Agnuside exerts antioxidant activity by forming up to 11 hydrogen bonds with topoisomerase enzyme residues and engages in Amide-Pi Stacked and Pi-Alkyl interactions, effectively inhibiting oxidative enzyme activity. The leaf also contains isoorientin, scutellarin, and chlorogenic acid, which collectively scavenge free radicals and modulate inflammatory pathways.

### Is there clinical trial evidence supporting Vitex negundo for inflammation?

Currently, no published randomized controlled human clinical trials exist for Vitex negundo extracts; the available evidence is limited to preclinical animal studies. In murine peritoneal inflammation models, methanolic leaf extracts at 9.6 g/kg and 28.8 g/kg produced anti-inflammatory outcomes statistically comparable to methylprednisolone (10 mg/kg), a corticosteroid reference drug. These findings are promising but cannot yet be applied to human dosing or therapeutic recommendations without formal clinical investigation.

### What is Vitex negundo traditionally used for in Ayurveda?

In Ayurveda, Vitex negundo (Nirgundi) is classified as a bitter, pungent herb with hot potency and has been prescribed for fever reduction (antipyretic), pain relief (analgesic), intestinal parasite clearance (anthelmintic), and management of rheumatic joint pain for over two millennia. It is referenced in classical texts including the Charaka Samhita and is officially listed in the Ayurvedic Pharmacopoeia of India. Traditional preparations include leaf decoctions (10–20 g dried leaf per 500 mL water), fresh leaf poultices for topical joint application, and powdered leaf in compound formulations.

### What is a safe dose of Vitex negundo extract for humans?

No standardized or clinically validated human dose for Vitex negundo extract has been established, as human pharmacokinetic and dose-finding studies have not been published. Traditional Ayurvedic practice typically administers dried leaf powder at approximately 3–6 g/day in decoction or powder form, though this lacks pharmacopoeial standardization in Western regulatory frameworks. Individuals should consult a qualified healthcare provider before use, particularly given the absence of formal human safety data and the plant's documented prolactin-lowering and potential uterine-stimulating properties.

### Can Vitex negundo interact with medications or be used during pregnancy?

Vitex negundo's dopaminergic (prolactin-lowering) constituents create a theoretical risk of pharmacodynamic interaction with dopamine antagonist medications such as antipsychotics (haloperidol, risperidone) and prokinetics (metoclopramide), potentially reducing their efficacy. Use during pregnancy is not recommended based on ethnomedicinal caution and evidence of uterine-stimulating and hormonal activity; lactating women should also avoid use given prolactin-lowering effects that could reduce milk production. No controlled drug interaction studies in humans have been conducted, so concurrent use with anti-inflammatory drugs, immunosuppressants, or hormone therapies warrants medical supervision.

### What is the bioavailability of Vitex negundo flavonoids and does extraction method affect absorption?

Methanolic extraction of Vitex negundo leaves yields higher concentrations of bioavailable flavonoids (isoorientin, isovitexin, and scutellarin) compared to aqueous methods, as demonstrated by HPLC quantification studies. Extraction method directly impacts the dose-dependent antioxidant potency measured in assays (R²=0.9993 at 0.25–50 µg/mL), suggesting that standardized methanolic extracts provide superior bioavailability for systemic ROS quenching. Solvent choice during processing influences both the quantity and quality of active compounds reaching circulation.

### Which populations are most likely to benefit from Vitex negundo supplementation based on its mechanisms?

Individuals with elevated oxidative stress, chronic inflammatory conditions, or compromised antioxidant defenses are optimal candidates, as Vitex negundo's flavonoid profile directly targets ROS scavenging through electron donation mechanisms. Those with inflammatory-driven conditions may benefit most from the dose-dependent anti-inflammatory effects observed at 9.6–28.8 g/kg equivalent exposures in preclinical models. People seeking natural antioxidant support without the adverse event profile of synthetic alternatives represent a secondary target population.

### How does Vitex negundo's antioxidant mechanism compare to its anti-inflammatory effects at the molecular level?

Vitex negundo's flavonoids function through dual parallel pathways: direct ROS neutralization via electron donation (measured in LC-ECD assays with high correlation coefficients), and secondary anti-inflammatory signaling triggered by reduced oxidative burden in immune cells. The antioxidant effect is quantifiable and dose-dependent across a 0.25–50 µg/mL range, while anti-inflammatory effects emerge at higher systemic concentrations (9.6+ g/kg in animal models) as oxidative stress reduction modulates inflammatory cytokine production. These mechanisms are synergistic rather than independent, with antioxidant activity serving as the upstream driver of downstream anti-inflammatory benefits.

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