Hermetica Superfood Encyclopedia
The Short Answer
Vitex negundo leaves contain the iridoid glucoside agnuside (quantified at 3.04 ± 0.02% in dried leaves), alongside flavonoids isoorientin and isovitexin, sesquiterpenoid viridiflorol, and phenolic acids that collectively drive free-radical scavenging and prostaglandin-pathway suppression. In mouse peritoneal inflammation models, leaf extract at 9.6 g/kg produced chronic anti-inflammatory effects comparable to methylprednisolone 10 mg/kg, representing the strongest quantified preclinical evidence for its traditional use in pain and inflammation.
CategoryHerb
GroupSoutheast Asian
Evidence LevelPreliminary
Primary KeywordVitex negundo benefits
Nirgundi — botanical close-up
Health Benefits
**Anti-inflammatory Activity**
Flavonoids and terpenoids in leaf extracts suppress inflammatory mediator production; mouse peritoneal models confirm chronic anti-inflammation at 9.6–28.8 g/kg leaf extract comparable to corticosteroid methylprednisolone at 10 mg/kg.
**Analgesic Effects**
Glycosides, phenolics, and phytosteroids contribute to analgesic properties recognized across Ayurvedic and Filipino hilot traditions; preclinical models support pain threshold elevation through peripheral mechanisms.
**Antioxidant Protection**
Isoorientin, chlorogenic acid, cynaroside, scutellarin, and agnuside provide robust free-radical scavenging capacity measured by LC-ECD fractionation, with high agnuside and isovitexin content correlating to peak antioxidant activity.
**Antipyretic Action**
Traditional decoctions of leaves are employed for fever reduction; bioactive phenolics and iridoids are postulated to modulate thermoregulatory pathways, consistent with the plant's broad anti-inflammatory profile.
**Antimicrobial and Antitubercular Potential**
The sesquiterpenoid viridiflorol demonstrates activity against Mycobacterium tuberculosis in preclinical assays, and essential oil constituents including terpinen-4-ol and epiglobulol contribute to broad antimicrobial effects.
**Prolactin Modulation**
Leaf extracts reduce serum prolactin in hyperprolactinemia and mastodynia models, paralleling the dopaminergic mechanism attributed to related species Vitex agnus-castus, though species-specific clinical data remain limited.
**Anthelmintic Activity**
Leaf preparations carry documented anthelmintic properties in traditional Ayurvedic use, attributed to bitter iridoids and phenolic astringents that disrupt parasitic worm physiology at gastrointestinal mucosal surfaces.
Origin & History
Natural habitat
Vitex negundo is native to tropical and subtropical Asia, ranging from Afghanistan and India through Southeast Asia to the Philippines, where it thrives in disturbed habitats, forest margins, riverbanks, and scrublands at low to mid elevations. It is a fast-growing aromatic shrub or small tree cultivated across South and Southeast Asia for medicinal, agricultural, and ornamental purposes, with wild populations also harvested extensively. In the Philippines it is integrated into traditional hilot healing practice, while in India it holds an established place in both Ayurvedic and Siddha medicine systems.
“Vitex negundo has been documented in Indian Ayurvedic texts for over two millennia under the Sanskrit name Nirgundi, where it is classified as a Vata-pacifying herb prescribed for arthritis, nerve pain, uterine disorders, and helminthic infections, with leaf poultices applied externally for joint swellings. In traditional Chinese medicine it appears as Huang Jing Zi, used for headaches, common cold, and musculoskeletal complaints, while across Southeast Asia—particularly in the Philippines—it is a cornerstone of hilot (traditional healing massage and herbalism), where fresh bruised leaves are applied topically and decoctions administered for cough, fever, and pain relief. The plant's Filipino vernacular name lagundi became widely recognized during the 1990s when the Philippine Department of Health endorsed it as one of ten approved herbal medicines, validating decoctions for cough and asthma management. Historical Western botanical records note the plant's aromatic, bitter, and pungent leaf chemistry as characteristic of its therapeutic identity across all traditional systems in which it appears.”Traditional Medicine
Scientific Research
The body of evidence for Vitex negundo consists almost entirely of in vitro assays and rodent preclinical studies; no published human randomized controlled trials with reported sample sizes or effect sizes were identified in the available literature as of the research date. The most rigorous quantitative preclinical data come from mouse peritoneal inflammation models demonstrating chronic anti-inflammatory efficacy of leaf extract at 9.6 g/kg and 28.8 g/kg body weight, benchmarked against methylprednisolone 10 mg/kg, and from HPLC-validated quantification of agnuside at 3.04 ± 0.02% (R² = 0.9999, RSD ≤ 2.50%) providing analytical-grade phytochemical standardization. GC-MS profiling of essential oils identified 48 compounds, with the top 19 accounting for 88.65% of composition, and in vitro callus propagation studies demonstrated up to 47.79% octadecadienoic acid yield, roughly double wild-plant levels, informing future sourcing strategies. Overall, the evidence base is promising but firmly preclinical, with urgent need for phase I/II human trials before efficacy claims can be substantiated.
Preparation & Dosage
Traditional preparation
**Traditional Decoction (Leaves)**
10–15 g of dried leaves simmered in 500 mL water for 15–20 minutes, consumed in divided doses; used in Filipino hilot for pain and cough, and in Ayurvedic practice for fever and inflammation
**Methanolic/Ethanolic Extract**
Research-grade preparations use 70–80% methanol or ethanol maceration; no standardized commercial capsule dose established, but extracts are characterized by agnuside content (target ≥ 3% by HPLC).
**Essential Oil (Topical)**
Diluted to 1–3% in carrier oil for topical application; 48 identified compounds with epiglobulol (30.31%) and terpinen-4-ol (9.42%) as principal constituents.
**Dried Leaf Powder**
Used in Ayurvedic formulations; agnuside quantified at 3.04 ± 0.02% per gram of dried leaf provides a standardization benchmark, though therapeutic dose range has not been established in human trials.
**In Vitro Callus Extract (Experimental)**
Micropropagated callus yields up to 47.79% octadecadienoic acid versus 21.93% in wild leaves; relevant only to pharmaceutical ingredient sourcing, not current consumer use.
**Timing Note**
Traditional preparations are typically administered twice daily with meals to minimize gastric irritation from bitter iridoids and astringent tannins.
Nutritional Profile
Vitex negundo leaves are not a significant dietary macronutrient source but contain nutritionally and pharmacologically relevant phytochemicals: phenolics at approximately 2.70 mg/g dry weight, proteins at 2.49 mg/g, and phytosterols (notably sitosterol) at 1.1 mg/g. Iridoid content centers on agnuside at approximately 30.4 mg/g of dried leaf (3.04%), while flavonoids isoorientin, isovitexin, cynaroside, and scutellarin contribute to total polyphenol load alongside chlorogenic acid. Essential oil constituents including epiglobulol (30.31% of oil fraction), terpinen-4-ol (9.42%), delta-iraleine (10.34%), and gamma-elemene (5.72%) are present in the aromatic resin of fresh leaves. The fatty-acid fraction is dominated by octadecadienoic acid (linoleic acid, 21.93% in wild leaf extracts) and hexadecanoic acid (palmitic acid), suggesting modest but present essential fatty acid content; bioavailability of polar iridoids and flavonoids from aqueous decoctions is expected to be moderate, with lipophilic terpenoids more bioavailable in ethanolic or oil-based preparations.
How It Works
Mechanism of Action
Agnuside, the principal iridoid glucoside of Vitex negundo, and co-occurring flavonoids isoorientin and isovitexin exert antioxidant effects primarily through direct hydrogen-atom donation to reactive oxygen species, with LC-ECD fractionation confirming that fractions of highest agnuside/isovitexin content display the greatest radical-scavenging capacity. The sesquiterpenoid viridiflorol modulates inflammatory pathways and shows anti-mycobacterial activity, likely through inhibition of mycobacterial cell-wall biosynthesis enzymes and suppression of pro-inflammatory cytokine signaling. Phytosterols such as sitosterol and oleanolic acid compete with cholesterol at membrane receptor sites and inhibit NF-κB-mediated transcription of inflammatory genes, while benzoic-acid-derived phenolics chelate transition metals to interrupt Fenton-type oxidative cascades. Prolactin-lowering activity is mechanistically hypothesized to involve partial dopamine D2-receptor agonism, consistent with the iridoid-rich chemistry shared with Vitex agnus-castus, though direct receptor-binding studies for V. negundo remain unpublished.
Clinical Evidence
No completed human clinical trials for Vitex negundo have been reported in the indexed literature; all pharmacological efficacy data derive from animal models and in vitro experiments. The most clinically translatable finding is the peritoneal mouse model demonstrating anti-inflammatory potency equivalent to a standard corticosteroid dose, though interspecies dose scaling renders direct human dose extrapolation unreliable without pharmacokinetic bridging studies. HPLC quantification work establishes the analytical foundation for future standardized clinical preparations, with agnuside at approximately 3% of dried leaf weight serving as a candidate marker compound for dosage standardization. Confidence in clinical outcomes for human populations must be rated low pending controlled human trials; current use rests on centuries of traditional empirical practice rather than randomized evidence.
Safety & Interactions
Vitex negundo lacks formal human clinical safety data; traditional use over centuries across Asia suggests reasonable tolerability at conventional decoction doses, but no maximum tolerated dose, no-observed-adverse-effect level (NOAEL), or formal toxicological profile has been established for human subjects. The mouse studies employing 28.8 g/kg leaf weight-to-body-weight ratios represent extremely high doses that require caution when interpreting safety margins, and direct dose extrapolation to humans is not valid without allometric scaling and pharmacokinetic studies. Given the plant's documented prolactin-lowering and possible dopaminergic activity, it should be used with caution alongside dopamine agonists or antagonists (e.g., antipsychotics, metoclopramide) and is contraindicated in pregnancy due to potential uterotonic and hormonal effects consistent with the Vitex genus. Individuals on hormone-sensitive therapies, immunosuppressants, or corticosteroids should consult a healthcare provider before use, and lactating women should avoid internal preparations pending safety data.
Synergy Stack
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Also Known As
Vitex negundo L.NirgundiLagundiFive-leaved chaste treeHuang Jing ZiSambhaluNegundi
Frequently Asked Questions
What is the active compound in Vitex negundo responsible for its anti-inflammatory effects?
The primary marker compound is agnuside, an iridoid glucoside quantified at 3.04 ± 0.02% in dried leaves by HPLC. Alongside agnuside, flavonoids isoorientin and isovitexin, and the sesquiterpenoid viridiflorol collectively suppress inflammatory mediators, with mouse models showing efficacy comparable to methylprednisolone 10 mg/kg at leaf extract doses of 9.6 g/kg body weight.
Is Vitex negundo the same as Vitex agnus-castus (chasteberry)?
No—Vitex negundo and Vitex agnus-castus are related but distinct species within the Vitex genus. Both share iridoid chemistry and some hormonal (prolactin-modulating) properties, but V. negundo is predominantly used across South and Southeast Asia for pain, inflammation, cough, and fever, while V. agnus-castus is the species with established clinical trial data for premenstrual syndrome and hyperprolactinemia in Western herbal medicine.
What is Vitex negundo (lagundi) used for in Filipino traditional medicine?
In Philippine traditional medicine and hilot healing practice, lagundi (Vitex negundo) leaf decoctions are administered orally for cough, asthma, fever, and pain relief. The Philippine Department of Health officially endorsed lagundi as one of ten approved herbal medicines in the 1990s, validating its use specifically for cough and mild bronchial conditions based on accumulated traditional and preliminary pharmacological evidence.
What is the recommended dosage of Vitex negundo for pain or inflammation?
No standardized human clinical dosage has been established because no human clinical trials have been completed. Traditional Ayurvedic and Filipino practice uses decoctions of 10–15 g of dried leaves in approximately 500 mL water, taken twice daily. Research-grade extracts are characterized by agnuside content of approximately 3% dry weight, but therapeutic dose ranges for human use await formal clinical investigation.
Is Vitex negundo safe during pregnancy?
Vitex negundo is not recommended during pregnancy. The plant belongs to a genus with documented uterotonic and prolactin/hormonal modulating properties, and its iridoid and phytosterol constituents may influence reproductive hormone balance. No formal human safety studies exist, and the precautionary principle warrants avoidance during pregnancy and lactation until controlled safety data are available.
Does Vitex negundo interact with corticosteroid medications?
While Vitex negundo demonstrates anti-inflammatory effects comparable to the corticosteroid methylprednisolone in animal studies, concurrent use with prescription corticosteroids should be discussed with a healthcare provider to avoid potential additive effects or interactions. The herb's mechanism of suppressing inflammatory mediators through flavonoids and terpenoids may theoretically enhance or interfere with corticosteroid function depending on individual factors and dosing.
What is the difference between Vitex negundo leaf extract and other plant parts (seeds, roots)?
Clinical research on Vitex negundo has primarily focused on leaf extracts, which contain the highest concentrations of active flavonoids and terpenoids responsible for anti-inflammatory and analgesic effects. While traditional preparations may use seeds or roots, the leaf extract form has the strongest scientific evidence for efficacy in pain and inflammation models, making it the most studied and recommended form for supplementation.
How quickly does Vitex negundo work for pain relief compared to other herbal analgesics?
Vitex negundo's analgesic effects are attributed to glycosides, phenolics, and phytosteroids that work through inflammation reduction rather than rapid pain masking, suggesting onset may be gradual with consistent use rather than immediate relief. Clinical onset timeframes specific to Vitex negundo have not been extensively documented in human studies, though its use in traditional medicine indicates effects develop over days to weeks of regular administration.
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