# Vitexnegheteroin (Vitex negundo — Five-Leaved Chaste Tree)

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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, Chinese chaste tree, Nishinda, Vitexnegheteroin

## Overview

Vitex negundo produces iridoid glucosides (principally agnuside at ~3.04% dry weight in leaves), flavonoids (isoorientin, isovitexin, casticin), and phenolic acids (chlorogenic acid) that exert antioxidant activity via hydrogen bond donation, [free radical scaveng](/ingredients/condition/antioxidant)ing, and molecular binding to redox-sensitive enzymes. Preclinical models demonstrate [anti-inflammatory](/ingredients/condition/inflammation) potency comparable to methylprednisolone 10 mg/kg at leaf extract doses of 9.6–28.8 g/kg body weight in murine chronic peritoneal inflammation assays, though no human randomized controlled trials have yet confirmed these effects.

## Health Benefits

- **Antioxidant Activity**: Iridoid glucoside agnuside and flavonoids isoorientin and isovitexin scavenge [reactive oxygen species](/ingredients/condition/antioxidant) and donate hydrogen atoms to stabilize free radicals; phenolic content of 2.70 mg/g in leaf extracts contributes measurable DPPH and FRAP antioxidant capacity in vitro.
- **[Anti-Inflammatory](/ingredients/condition/inflammation) Effects**: Methanolic leaf extracts at 9.6 and 28.8 g/kg body weight produced anti-inflammatory effects comparable to methylprednisolone 10 mg/kg in murine chronic peritoneal models; terpenoids and flavonoids are believed to suppress pro-inflammatory mediator synthesis.
- **Analgesic Properties**: Traditional Ayurvedic application for pain management is supported by preclinical evidence showing extract-mediated inhibition of nociceptive pathways; viridiflorol (sesquiterpenoid) and phenolic constituents are implicated in central and peripheral analgesic mechanisms.
- **Antipyretic Action**: Aqueous and methanolic leaf preparations have demonstrated fever-reducing activity in animal models, consistent with historical use for febrile conditions; flavonoid-mediated cyclooxygenase modulation is the proposed molecular basis.
- **Prolactin Regulation**: Extracts reduce serum prolactin levels in hyperprolactinemia models, paralleling the pharmacological profile of Vitex agnus-castus; this property supports traditional use for mastodynia and menstrual cycle normalization.
- **[Antimicrobial](/ingredients/condition/immune-support) and Anthelmintic Activity**: Viridiflorol and phenolic acids exhibit activity against bacterial and mycobacterial strains in vitro, while terpenoid-rich fractions demonstrate anthelmintic effects against gastrointestinal parasites in preclinical assays.
- **Antitumor Potential**: Casticin and oleanolic acid, identified in V. negundo extracts, have shown cytotoxic and apoptosis-inducing properties in cancer cell lines in vitro, though no clinical evidence currently validates antitumor efficacy in humans.

## Mechanism of Action

Agnuside, the primary iridoid glucoside quantified at 3.04 ± 0.02% in dried leaves, binds target enzymes including topoisomerase via 11 hydrogen bonds alongside amide-pi stacked and pi-alkyl interactions, achieving docking scores exceeding 100 in silico, suggesting potent enzyme inhibition relevant to antioxidant and anti-inflammatory cascades. Flavonoids isoorientin, isovitexin, and scutellarin donate phenolic hydroxyl hydrogen atoms to quench [reactive oxygen species](/ingredients/condition/antioxidant) and chelate transition metals, interrupting Fenton-type oxidative chain reactions. Viridiflorol, a bicyclic sesquiterpenoid, modulates [pro-inflammatory cytokine](/ingredients/condition/inflammation) production and demonstrates anti-mycobacterial membrane-disrupting activity, while casticin suppresses NF-κB signaling pathways to reduce transcription of inflammatory mediator genes. Collectively, the synergistic interaction between iridoids, flavonoids, and phenolic acids across multiple molecular targets accounts for the broad-spectrum pharmacological profile observed in preclinical models.

## Clinical Summary

No human clinical trials with defined sample sizes, randomization, or controlled endpoints have been identified for Vitex negundo or its constituent compound vitexnegheteroin in the peer-reviewed literature accessible at this time. Preclinical evidence from murine models demonstrates [anti-inflammatory](/ingredients/condition/inflammation) effects at high-dose leaf extract administration (9.6–28.8 g/kg body weight) with effect sizes comparable to methylprednisolone 10 mg/kg on peritoneal inflammation scoring metrics, though these doses are not translatable to standard human supplementation without further pharmacokinetic bridging studies. In vitro antioxidant assays confirm [free radical scaveng](/ingredients/condition/antioxidant)ing capacity for agnuside, isoorientin, chlorogenic acid, and cynaroside, but IC50 values for iridoid glycosides exceeding 20 µM indicate moderate rather than potent antioxidant activity by contemporary benchmark standards. Confidence in clinical outcomes for humans remains low; well-designed phase I/II trials establishing safety, pharmacokinetics, and efficacious dose ranges are a prerequisite before therapeutic claims can be substantiated.

## Nutritional Profile

Vitex negundo leaves contain phenolic compounds at approximately 2.70 mg/g dry weight, proteins at 2.49 mg/g, phytosterols (principally sitosterol and β-sitosterol) at 1.1 mg/g, and lipids at approximately 0.5% w/w. The dominant fatty acid identified by GC-MS is octadecadienoic acid (linoleic acid) at 21.93% of volatile extractable compounds in wild leaves, rising to 40–48% in in vitro callus cultures, accompanied by hexadecanoic acid (palmitic acid) as a secondary lipid constituent. Key bioactive phytochemicals include iridoid glucosides (agnuside at 3.04 ± 0.02% dry leaf weight; negundoside; vetugnoside), flavonoids (isoorientin, isovitexin calibration range 0.25–50 µg/mL; casticin; scutellarin; cynaroside; 5-hydroxy-7,4'-dimethoxyflavone), phenolic acids (chlorogenic acid, benzoic acid), terpenoids (viridiflorol, oleanolic acid), vitamin C, the alkaloid anhalonine, and nishindine. Bioavailability of iridoid glycosides such as agnuside is influenced by intestinal glycosidase hydrolysis liberating the aglycone, while flavonoid absorption is modulated by gut microbiota-mediated deglycosylation; no human pharmacokinetic data are currently available for these specific constituents from V. negundo.

## Dosage & Preparation

- **Dried Leaf Powder (Traditional)**: Used in Ayurvedic formulations at approximately 3–6 g/day in divided doses; standardization to agnuside content (target ≥3% by HPLC) is recommended for consistency.
- **Methanolic/Hydroalcoholic Extract**: Research extracts prepared at ratios yielding agnuside concentrations comparable to the 3.04% found in dried leaves; no commercially standardized human dose has been established from clinical trials.
- **Aqueous Decoction (Traditional)**: Leaves boiled in water (10–20 g dried leaf per 500 mL) and consumed as a tea for [anti-inflammatory](/ingredients/condition/inflammation) and antipyretic purposes in Ayurvedic practice; duration traditionally 2–4 weeks for acute conditions.
- **Standardized Extract Capsules (Emerging)**: Experimental in vitro callus culture systems using BAP (2.0 mg/L) and 2,4-D (0.2 mg/L) have demonstrated enhanced bioactive yield (octadecadienoic acid up to 47.79%), suggesting potential for standardized commercial production, though no validated human supplement dose ranges are yet established.
- **Timing Note**: Traditional use typically involves morning and evening administration with food to minimize potential gastrointestinal irritation from bitter terpenoid constituents; no clinical pharmacokinetic data on optimal timing is available.
- **Important Caveat**: All dosing information above derives from traditional practice or animal model extrapolation; no evidence-based human dosing guidelines currently exist for this ingredient.

## Safety & Drug Interactions

Vitex negundo has a long history of traditional use without widely reported serious adverse events, but formal toxicological profiling in humans is absent from the published literature, precluding definitive safety characterization at supplemental doses. Animal model studies employing doses as high as 9.6–28.8 g/kg body weight (leaf weight equivalent) did not report acute toxicity, but these figures represent extreme multiples of any plausible human dose and should not be interpreted as confirming safety margins for chronic human use. Given the plant's documented prolactin-lowering activity, clinically meaningful interactions with [dopamine](/ingredients/condition/mood)rgic medications (e.g., dopamine agonists such as cabergoline or bromocriptine used in hyperprolactinemia management) and hormonal contraceptives are theoretically possible and warrant caution. The alkaloid constituent anhalonine carries psychotropic activity classification, and the [anti-inflammatory](/ingredients/condition/inflammation) potency approaching corticosteroid equivalence at high doses raises theoretical concern for [immune modulation](/ingredients/condition/immune-support) with prolonged use; use during pregnancy and lactation is not recommended due to prolactin-modulating and uterine-stimulating properties documented in traditional medicine contexts and the absence of human safety data.

## Scientific Research

The evidence base for Vitex negundo consists predominantly of in vitro assays and small animal model studies, with no published human randomized controlled trials identified in the available literature. GC-MS characterization studies have identified and quantified 24 volatile compounds in wild leaf extracts, and HPLC-validated methods (R²=0.9999, recovery 96.58–101.86%) have confirmed agnuside concentrations reproducibly across extraction batches, providing reliable phytochemical benchmarking. Murine [anti-inflammatory](/ingredients/condition/inflammation) experiments using doses of 9.6–28.8 g/kg body weight (leaf weight equivalents) demonstrated statistically significant reductions in chronic peritoneal inflammation markers comparable to the corticosteroid methylprednisolone at 10 mg/kg, but these extreme animal doses cannot be directly extrapolated to safe or practical human equivalents. Molecular docking and in vitro [antioxidant](/ingredients/condition/antioxidant) studies support mechanistic plausibility, but the overall clinical evidence base remains at an early preclinical stage, warranting caution before drawing conclusions about human therapeutic efficacy.

## Historical & Cultural Context

Vitex negundo has occupied a central position in Ayurvedic medicine for over two millennia, referenced in classical texts including the Charaka Samhita and Sushruta Samhita under the Sanskrit name 'Nirgundi,' where it was prescribed for pain, [inflammation](/ingredients/condition/inflammation), joint disorders, fever, and worm infestations. In Traditional Chinese Medicine, the plant (known as huang jing zi or man jing zi in related species contexts) was similarly employed for wind-heat conditions, headache, and eye disorders, reflecting convergent ethnopharmacological recognition across independent healing traditions. Traditional preparation methods ranged from leaf poultices applied topically for joint pain to decoctions and leaf juice consumed internally for fever reduction and anthelmintic purposes, with the aromatic volatile oil components providing characteristic bitter, pungent, and astringent organoleptic properties valued in both systems. Historical European botanical records from Portuguese and Dutch colonial natural historians in Asia during the 16th–18th centuries documented local populations using the plant's smoke for insect repellency and the root bark for snakebite management, underscoring its broad utilitarian significance across cultures.

## Synergistic Combinations

Vitex negundo extracts may exhibit additive or synergistic antioxidant effects when combined with vitamin C (ascorbic acid), which regenerates oxidized phenolic antioxidants back to their active reduced forms through electron transfer, potentially extending the effective antioxidant lifespan of agnuside and chlorogenic acid in biological systems. Pairing with black pepper extract standardized to piperine (5–20 mg) may enhance oral bioavailability of flavonoid glycosides such as isovitexin and casticin by inhibiting intestinal P-glycoprotein efflux and CYP3A4-mediated first-pass [metabolism](/ingredients/condition/weight-management), a mechanism well-documented for structurally similar plant flavonoids. In traditional Ayurvedic formulations, V. negundo is frequently combined with Withania somnifera (ashwagandha) and Boswellia serrata for compounded anti-inflammatory effect, with withanolides and boswellic acids potentially addressing complementary [inflammatory pathway](/ingredients/condition/inflammation)s (NF-κB and 5-LOX, respectively) alongside V. negundo's COX-modulatory and [free radical scaveng](/ingredients/condition/antioxidant)ing actions.

## Frequently Asked Questions

### What is agnuside and why is it important in Vitex negundo?

Agnuside is the primary iridoid glucoside in Vitex negundo leaves, quantified at 3.04 ± 0.02% dry weight by validated HPLC methods with near-perfect linearity (R²=0.9999). It is considered the principal bioactive marker compound responsible for antioxidant and anti-inflammatory activity, exerting its effects through hydrogen bond formation with enzyme active sites and molecular docking interactions with topoisomerase residues at scores exceeding 100 in silico. Agnuside concentration is used as the standardization benchmark when evaluating extract quality for research and potential supplementation purposes.

### How does Vitex negundo compare to anti-inflammatory drugs in research?

In murine chronic peritoneal inflammation models, methanolic leaf extracts of Vitex negundo at doses of 9.6 g/kg and 28.8 g/kg body weight produced anti-inflammatory effects statistically comparable to the corticosteroid methylprednisolone at 10 mg/kg, which is a meaningful pharmacological benchmark. However, these animal doses represent extremely high leaf-weight-to-body-weight ratios that cannot be directly translated to human dosing without bridging pharmacokinetic studies. No human clinical trials have compared Vitex negundo preparations to anti-inflammatory pharmaceuticals, so this preclinical comparison should not be interpreted as clinical equivalence.

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

Vitex negundo is not recommended during pregnancy based on its documented prolactin-lowering and potential uterine-stimulating properties noted in traditional medical contexts, as well as the complete absence of human safety data from controlled trials. The plant contains the alkaloid anhalonine, which has known psychotropic activity, and its anti-inflammatory potency at higher doses raises additional concerns for fetal development and immune function during pregnancy. Women who are pregnant, trying to conceive, or breastfeeding should avoid Vitex negundo supplements and consult a qualified healthcare provider before use.

### What is the difference between Vitex negundo and Vitex agnus-castus (chasteberry)?

Vitex negundo (five-leaved chaste tree) and Vitex agnus-castus (chasteberry or monk's pepper) are distinct species within the Vitex genus sharing overlapping pharmacological profiles, particularly prolactin-reducing and anti-inflammatory activity, but differing in botanical characteristics, geographic origin, and phytochemical composition. V. agnus-castus is predominantly Mediterranean in origin and has been more extensively studied in human clinical trials for premenstrual syndrome and hyperprolactinemia, while V. negundo is native to tropical Asia and has a broader traditional application scope including analgesic, anthelmintic, and antipyretic uses. The iridoid agnuside is found in both species, but V. negundo additionally contains unique compounds such as negundoside, vetugnoside, and the alkaloid anhalonine not prominently characterized in V. agnus-castus.

### What forms of Vitex negundo are available as supplements and what dose should I take?

Vitex negundo is available primarily as dried leaf powder and hydroalcoholic leaf extracts in traditional herbal markets across South and Southeast Asia, with emerging commercial interest in standardized extracts targeting ≥3% agnuside content by HPLC verification. Traditional Ayurvedic practice used approximately 3–6 g of dried leaf powder daily in divided doses, or aqueous decoctions prepared from 10–20 g dried leaves per 500 mL of water. No evidence-based human dosing guideline exists because no clinical trials have established a safe and effective dose range; any supplementation should be undertaken under guidance from a qualified healthcare practitioner familiar with botanical medicine.

### Does Vitex negundo contain the same active compounds as other Vitex species, and are they equally potent?

While Vitex negundo and Vitex agnus-castus both contain iridoid glucosides like agnuside, Vitex negundo's leaf extracts are specifically rich in flavonoids isoorientin and isovitexin, which differ in concentration from chasteberry. Research indicates Vitex negundo leaf extracts demonstrate measurable antioxidant capacity with phenolic content of 2.70 mg/g, though direct potency comparisons between species for specific health outcomes remain limited in clinical literature.

### How do the antioxidant compounds in Vitex negundo actually work to neutralize free radicals?

The iridoid glucoside agnuside and flavonoids in Vitex negundo scavenge reactive oxygen species by donating hydrogen atoms that stabilize free radicals, converting them into harmless molecules. This mechanism is demonstrated in laboratory antioxidant assays (DPPH and FRAP), though the clinical significance of these in vitro antioxidant activities in human supplementation requires further research.

### What populations might benefit most from Vitex negundo supplementation based on its mechanisms?

Individuals seeking antioxidant and anti-inflammatory support may benefit from Vitex negundo, particularly those interested in traditional herbal approaches to hormonal or inflammatory concerns. However, the strongest evidence exists for specific populations and health conditions in traditional use; prospective users should consult healthcare providers to determine appropriateness based on individual health status and concurrent medications.

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