# 4,5-Diethyl-3O-Ethoxy-Pyroflavone (Vitex negundo)

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/45-diethyl-3o-ethoxy-pyroflavone-vitex-negundo
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-04-04
**Evidence Score:** 1 / 10
**Category:** Compound
**Also Known As:** 4,5-diethyl-3'-ethoxy-pyroflavone, 3-ethoxy-4,5-diethylpyroflavone, Vitex negundo flavone isolate, pyroflavone VN-1

## Overview

4,5-Diethyl-3O-ethoxy-pyroflavone is a flavone isolated from Vitex negundo that exhibits dose-dependent antifilarial activity in preclinical assays, structurally belonging to the pyroflavone subclass with ethoxy and ethyl substituents that may confer selective bioactivity against filarial parasites. Preclinical in vitro studies report significant antifilarial activity in a dose-dependent manner, though no quantified IC50 values, mechanistic targets, or clinical human data have been published to date.

## Health Benefits

- **Antifilarial Activity**: Demonstrates dose-dependent activity against filarial parasites in preclinical assays, making it one of a small number of plant-derived flavones with documented antiparasitic screening data from Vitex negundo extracts.
- **Phytochemical Diversity Contribution**: Co-occurs in V. negundo alongside iridoid glycosides such as nishandaside and nishindacin A/I, contributing to the plant's broad-spectrum bioactive profile that collectively supports [anti-inflammatory](/ingredients/condition/inflammation) and [antimicrobial](/ingredients/condition/immune-support) endpoints in preclinical research.
- **Potential Anti-inflammatory Scaffold**: As a pyroflavone derivative, its structural class is associated with cyclooxygenase modulation in related flavone analogues, suggesting plausible anti-inflammatory potential pending direct mechanistic investigation.
- **Antioxidant Structural Potential**: The ethoxy substitution pattern on the flavone ring system is consistent with [free radical scaveng](/ingredients/condition/antioxidant)ing capacity observed in structurally analogous methoxy- and ethoxy-flavones, though direct DPPH or ORAC assays for this specific compound are unreported.
- **Antiparasitic Lead Compound Value**: Its isolation from V. negundo positions it as a chemotype lead for synthetic or semi-synthetic antifilarial drug development, given the global burden of lymphatic filariasis affecting over 120 million people with limited pharmacological options.

## Mechanism of Action

The precise molecular mechanism of 4,5-diethyl-3O-ethoxy-pyroflavone against filarial organisms has not been characterized in published literature. Structurally analogous flavones with ethoxy substitutions at the 3-position have been investigated in related contexts for their ability to inhibit filarial motility through disruption of neuromuscular signaling in adult worms, potentially via [acetylcholine](/ingredients/condition/cognitive)sterase inhibition or interference with GABA-gated chloride channels. The ethyl substituents at the 4 and 5 positions of the pyroflavone core may influence lipophilicity and membrane permeability, potentially enhancing penetration into filarial cuticle layers relative to less substituted parent flavones. These mechanistic inferences are extrapolated from structural analogue data and require direct experimental validation through target identification studies such as thermal shift assays or molecular docking against characterized filarial proteomes.

## Clinical Summary

No clinical trials have been conducted on 4,5-diethyl-3O-ethoxy-pyroflavone in human subjects, and it has not progressed beyond in vitro phytochemical screening to the authors' knowledge. The compound has been identified in antifilarial bioassay-guided fractionation studies of Vitex negundo, where whole-plant extracts demonstrated activity, and the flavone was identified as a contributing bioactive fraction; however, no isolated-compound clinical data exists. There are no published effect sizes, confidence intervals, CONSORT-compliant trial reports, or dose-escalation safety studies. Clinical confidence in any therapeutic application is therefore negligible, and any prospective use would require a full preclinical development pipeline including in vivo efficacy, pharmacokinetics, and toxicology before human investigation could be ethically justified.

## Nutritional Profile

4,5-Diethyl-3O-ethoxy-pyroflavone is a pure isolated phytochemical compound with no conventional nutritional profile in terms of macronutrients, micronutrients, or caloric contribution. As a flavone polyphenol, its chemical class broadly encompasses [antioxidant](/ingredients/condition/antioxidant) capacity mediated by the aromatic ring system capable of electron donation, though direct radical scavenging assays for this molecule are unpublished. The ethoxy group at the 3-position and ethyl substituents at positions 4 and 5 increase molecular weight and lipophilicity relative to parent flavone (MW ~222 Da), suggesting enhanced membrane permeability but potentially reduced aqueous solubility and oral bioavailability without formulation aids. No phytochemical concentration data in plant tissue (mg/g dry weight) or extract preparations has been reported, precluding any quantitative nutritional or phytochemical profiling.

## Dosage & Preparation

- **Laboratory Isolation Form**: Obtained via ethyl acetate or methanolic extraction of Vitex negundo leaves or seeds followed by silica gel column chromatography; no commercial standardized extract exists.
- **Research Extract Concentration**: No standardization percentage or minimum effective concentration has been established for this isolated compound in any published study.
- **Traditional Herbal Preparation (Parent Plant)**: V. negundo leaves are prepared as decoctions (10–20 g dried leaf boiled in 200 mL water) or as poultice sachets in Ayurvedic practice, though flavone content of these preparations is unquantified.
- **Effective Dose Range**: No human or animal effective dose range has been established; in vitro antifilarial assays do not specify molar or gravimetric concentrations in available published summaries.
- **Timing and Administration**: No pharmacokinetic data exists to guide timing, frequency, or route of administration; oral bioavailability of this specific compound is entirely uncharacterized.
- **Supplement Forms**: Not commercially available as a standalone supplement; not listed in any nutraceutical, pharmaceutical, or botanical product databases.

## Safety & Drug Interactions

No safety data, toxicological studies, maximum tolerated doses, or adverse event profiles have been published for 4,5-diethyl-3O-ethoxy-pyroflavone as an isolated compound, and its use in humans cannot be considered established or safe based on available evidence. No drug interaction studies exist; however, as a flavone, structural class members have been associated with inhibition of cytochrome P450 enzymes (particularly CYP1A2 and CYP3A4) and P-glycoprotein in related compounds, which theoretically could alter [metabolism](/ingredients/condition/weight-management) of co-administered pharmaceuticals including anticoagulants, antiretrovirals, and immunosuppressants. Contraindications are undefined, but caution is warranted in pregnancy and lactation given the antiparasitic bioactivity of the parent plant V. negundo and its traditional classification as a potentially uterotonic herb in some regional medicinal systems. The compound should not be used therapeutically outside of controlled research settings until formal preclinical safety pharmacology and genotoxicity studies are completed.

## Scientific Research

The scientific evidence base for 4,5-diethyl-3O-ethoxy-pyroflavone is extremely limited and exists exclusively at the preclinical level, with no peer-reviewed publications reporting controlled human trials, animal pharmacokinetic studies, or formal toxicological profiling for this specific compound. Available data originates from phytochemical screening studies on Vitex negundo extracts where the compound was isolated alongside other bioactives and tested in in vitro antifilarial assays, with results described qualitatively as 'significant dose-dependent activity' without published IC50 values, confidence intervals, or comparative benchmarks against standard antifilarial agents such as diethylcarbamazine. No PubMed-indexed randomized controlled trials, systematic reviews, or meta-analyses address this compound specifically, and it does not appear in any clinical trial registries. The overall evidence quality is pre-preliminary, suitable only for hypothesis generation and prioritization as a phytochemical lead rather than clinical application.

## Historical & Cultural Context

4,5-Diethyl-3O-ethoxy-pyroflavone itself has no independent historical or cultural use history, as it is a recently isolated phytochemical constituent rather than a recognized traditional remedy. Its source plant, Vitex negundo—known as Nirgundi in Sanskrit Ayurvedic texts and Sambhalu in Hindi—has a documented history of over 2,000 years in Indian, Chinese, and Southeast Asian traditional medicine systems, where leaf preparations were applied for joint pain, rheumatic conditions, malaria, skin diseases, and helminthic infections. In Ayurveda, V. negundo is classified as a 'Shothahara' (anti-edematous) and 'Krimighna' (antiparasitic) herb, which contextually aligns with the subsequent discovery of antifilarial activity in its isolated constituents. The Charaka Samhita and Sushruta Samhita both reference Nirgundi preparations, lending historical plausibility to contemporary antifilarial and [anti-inflammatory](/ingredients/condition/inflammation) screening programs targeting its phytochemistry.

## Synergistic Combinations

No published synergy data exists for 4,5-diethyl-3O-ethoxy-pyroflavone in combination with other compounds. Within the context of its parent plant Vitex negundo, co-occurring bioactives including the iridoid glycoside nishandaside and the flavonoid vitexin have independently demonstrated [anti-inflammatory](/ingredients/condition/inflammation) and antiparasitic properties, suggesting potential additive or synergistic antifilarial effects through complementary mechanisms such as neuromuscular disruption and [immune modulation](/ingredients/condition/immune-support), though this has not been experimentally validated for this specific flavone. In the broader antifilarial pharmacology literature, flavone compounds have been investigated in combination with diethylcarbamazine (DEC) as adjunct agents, which represents a plausible combinatorial hypothesis for this compound pending mechanistic characterization.

## Frequently Asked Questions

### What is 4,5-diethyl-3O-ethoxy-pyroflavone and where does it come from?

4,5-Diethyl-3O-ethoxy-pyroflavone is a flavone compound isolated from Vitex negundo, a medicinal shrub native to tropical Asia commonly called Nirgundi or Five-leaved Chaste Tree in Ayurvedic medicine. It is obtained through chromatographic fractionation of plant extracts and has been studied in preclinical antifilarial bioassays as one of several bioactive constituents of the plant.

### Does 4,5-diethyl-3O-ethoxy-pyroflavone have proven antifilarial activity?

Preclinical in vitro studies report dose-dependent antifilarial activity for this compound isolated from Vitex negundo extracts, but no IC50 values, in vivo animal studies, or human clinical trials have been published to confirm or quantify this activity. The evidence is therefore preliminary and insufficient to support any therapeutic claims at this stage of research.

### Is 4,5-diethyl-3O-ethoxy-pyroflavone available as a supplement?

No, 4,5-diethyl-3O-ethoxy-pyroflavone is not commercially available as a dietary supplement or nutraceutical product in any form. It exists only as a laboratory-isolated research compound from Vitex negundo and has not been developed into any standardized extract, capsule, or powder formulation.

### What are the safety risks of 4,5-diethyl-3O-ethoxy-pyroflavone?

No formal toxicological data, adverse event profiles, or drug interaction studies have been published for this specific compound, meaning its safety profile in humans is entirely unknown. Given the absence of any safety pharmacology data and its structural class as a lipophilic flavone with potential CYP enzyme interactions, it should not be self-administered outside controlled clinical research contexts.

### How does 4,5-diethyl-3O-ethoxy-pyroflavone differ from other Vitex negundo compounds?

Unlike better-characterized V. negundo constituents such as the iridoid glycoside nishandaside or the flavonoid vitexin, 4,5-diethyl-3O-ethoxy-pyroflavone is distinguished by its pyroflavone core with ethyl groups at positions 4 and 5 and an ethoxy substitution at the 3-oxygen position, a combination that increases its lipophilicity relative to simpler hydroxylated flavones. This unique substitution pattern is believed to contribute to its selective antiparasitic activity, though its mechanism of action has not been experimentally confirmed.

### What is the bioavailability of 4,5-diethyl-3O-ethoxy-pyroflavone from Vitex negundo supplements?

Bioavailability data for this specific compound is limited, as most research has focused on antifilarial activity in laboratory settings rather than human absorption studies. The ethoxy substitution pattern may influence how readily the compound is absorbed compared to unmodified flavones, but absorption rates have not been systematically characterized in clinical or animal models. Extraction methods and formulation type (powder, extract, standardized preparation) likely affect bioavailability, though comparative data is unavailable.

### Does 4,5-diethyl-3O-ethoxy-pyroflavone interact with antiparasitic medications?

Specific drug interaction data for this compound with antiparasitic agents is not currently documented in the scientific literature. Because it demonstrates independent antifilarial activity, concurrent use with prescription antiparasitic drugs should be approached cautiously and discussed with a healthcare provider to avoid additive or unexpected effects. No pharmacokinetic interaction studies have been conducted to date.

### How does 4,5-diethyl-3O-ethoxy-pyroflavone contribute to the overall effectiveness of whole Vitex negundo extracts?

This compound is one component within a complex phytochemical matrix that includes iridoid glycosides like nishandaside and nishindacin A/I, which may work synergistically with it. While 4,5-diethyl-3O-ethoxy-pyroflavone shows documented antifilarial activity in isolation, the traditional efficacy of V. negundo preparations may depend on this combination of multiple active constituents rather than any single compound alone. Research isolating this flavone's contribution relative to other plant compounds in whole-extract formulations remains limited.

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