# Tephrosin

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/tephrosin
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-03-29
**Evidence Score:** 2 / 10
**Category:** Compound
**Also Known As:** Tephrosin A, 12a-Hydroxytephrosin, Tephrosia rotenoid, Fish poison rotenoid, Fabaceae rotenoid compound

## Overview

Tephrosin is a rotenoid flavonoid derived primarily from Tephrosia vogelii and related leguminous plants, exerting anticancer activity chiefly through [mitochondrial](/ingredients/condition/energy) complex I inhibition and disruption of the PI3K/Akt/mTOR signaling axis. Preclinical research highlights its ability to suppress tumor growth and restore chemotherapy sensitivity in resistant cancer cell lines.

## Health Benefits

• Pancreatic cancer inhibition: Reduced tumor volume by up to 60.2% in mouse xenograft models (PMID: 33391424) - preclinical evidence only
• Ovarian cancer chemosensitization: Restored paclitaxel sensitivity in resistant SKOV3-TR cells with 36% apoptosis induction (PMID: 38137377) - in vitro evidence only
• Lung cancer suppression: Induced autophagic cell death via ROS and Hsp90 inhibition in A549 cells (PMID: 21061222) - in vitro evidence only
• [Anti-inflammatory](/ingredients/condition/inflammation) effects: Attenuated sepsis-induced acute lung injury in rat models (PMID: 29432911) - animal evidence only
• EGFR pathway modulation: Promoted EGFR internalization and degradation in cancer cells (PMID: 20056314) - in vitro evidence only

## Mechanism of Action

Tephrosin inhibits mitochondrial NADH:ubiquinone oxidoreductase (Complex I), disrupting cellular [energy metabolism](/ingredients/condition/energy) and triggering [reactive oxygen species](/ingredients/condition/antioxidant) (ROS)-mediated apoptosis in cancer cells. It also downregulates the PI3K/Akt/mTOR signaling pathway, suppressing anti-apoptotic proteins such as Bcl-2 and Bcl-xL while upregulating pro-apoptotic Bax. Additionally, in paclitaxel-resistant ovarian cancer cells, tephrosin modulates P-glycoprotein (P-gp) efflux pump activity and reverses multidrug resistance by altering MDR1 gene expression.

## Clinical Summary

All current evidence for tephrosin is preclinical, with no completed human clinical trials published as of 2024. In mouse xenograft models of pancreatic cancer, tephrosin administration reduced tumor volume by up to 60.2% compared to controls (PMID: 33391424). In vitro studies using paclitaxel-resistant SKOV3-TR ovarian cancer cells demonstrated that tephrosin co-treatment restored drug sensitivity and induced 36% apoptosis, suggesting chemosensitization potential (PMID: 38137377). The evidence base is limited to cell culture and rodent models, meaning efficacy and safety in humans remain entirely unestablished.

## Nutritional Profile

Tephrosin is not a nutrient or food substance; it is a naturally occurring rotenoid isoflavonoid (chemical formula: C₂₃H₂₂O₇, molecular weight: ~410.42 g/mol) primarily isolated from plants of the genus Tephrosia (e.g., Tephrosia purpurea, Tephrosia vogelii) and related leguminous species. It has no conventional nutritional profile (no macronutrients, vitamins, minerals, fiber, or protein content) as it is studied exclusively as a bioactive phytochemical/pharmacological compound. Key biochemical characteristics: • Classification: Rotenoid isoflavonoid; structural analog of deguelin and rotenone. • Typical concentrations in source plants: Found in trace amounts (usually low mg/g range in dried root or leaf extracts; precise concentrations vary by species, part, and extraction method — e.g., approximately 0.01–0.5% w/w of crude root extract in Tephrosia spp.). • Core bioactive structure: Contains a cis-fused B/C ring junction characteristic of rotenoids, with hydroxyl and methoxy substituents that contribute to its biological activity including [mitochondrial](/ingredients/condition/energy) complex I inhibition and Hsp90 interaction. • Solubility/Bioavailability: Poorly water-soluble; lipophilic compound typically requiring organic solvents (DMSO, ethanol) for dissolution. Oral bioavailability in humans is not established; preclinical studies use intraperitoneal or direct cell-culture administration. Absorption, distribution, [metabolism](/ingredients/condition/weight-management), and excretion (ADME) data in humans are currently unavailable. • Related co-occurring bioactives in Tephrosia extracts: deguelin, rotenone, tephrosin itself, and other rotenoids/flavonoids, which may exhibit synergistic or additive effects in crude preparations. • No established dietary reference intake, recommended daily allowance, or tolerable upper intake level exists, as tephrosin is an investigational compound, not a dietary supplement or food ingredient.

## Dosage & Preparation

No clinically studied human dosages exist. Preclinical studies used: In vitro: 1-20 µM for 24-48 hours on cancer cell lines. In vivo (mice): 10-20 mg/kg intraperitoneally daily for 13 days. Consult a healthcare provider before starting any new supplement.

## Safety & Drug Interactions

Tephrosin has not been evaluated for safety in human clinical trials, and no established safe dosage range exists for human supplementation. As a rotenoid and [mitochondrial](/ingredients/condition/energy) Complex I inhibitor, it shares a mechanism class with rotenone, which has documented neurotoxicity in animal models at high doses, raising theoretical safety concerns. It may potentiate the effects of chemotherapeutic agents such as paclitaxel, meaning concurrent use with oncology drugs should only occur under direct medical supervision. Tephrosin is contraindicated during pregnancy and breastfeeding due to complete absence of safety data, and individuals with mitochondrial disorders should avoid it entirely.

## Scientific Research

No human clinical trials have been conducted with tephrosin; all evidence comes from preclinical studies. Key studies include a mouse xenograft model (PMID: 33391424) showing 60.2% tumor reduction with 10-20 mg/kg daily for 13 days, and in vitro work (PMID: 38137377) demonstrating restored chemosensitivity in resistant ovarian cancer cells at 1-10 µM concentrations.

## Historical & Cultural Context

While isolated tephrosin has no documented traditional medicinal use, the source plants like Tephrosia vogelii have been traditionally used in African systems primarily for piscicidal (fish-poisoning) purposes rather than internal medicine. The compound was historically noted for its toxicity to aquatic organisms.

## Synergistic Combinations

Paclitaxel, 2-deoxy-D-glucose, ROS-inducing compounds, Hsp90 inhibitors, EGFR modulators

## Frequently Asked Questions

### What plant does tephrosin come from?

Tephrosin is predominantly isolated from Tephrosia vogelii, a leguminous shrub native to tropical Africa, as well as from other Tephrosia species including Tephrosia purpurea. The compound accumulates in the seeds, roots, and leaves of these plants, which have historically been used as fish poisons and insecticides due to their rotenoid content.

### Can tephrosin help with cancer treatment?

Tephrosin has shown anti-tumor activity exclusively in preclinical settings, including a 60.2% reduction in pancreatic tumor volume in mouse xenograft models and restored paclitaxel sensitivity in resistant ovarian cancer cells in vitro. No human clinical trials have been conducted, so it cannot currently be recommended as a cancer treatment or adjunct therapy outside of a formal research context.

### How does tephrosin cause cancer cell death?

Tephrosin induces apoptosis primarily by inhibiting mitochondrial Complex I, which collapses the mitochondrial membrane potential and triggers the intrinsic apoptosis pathway involving cytochrome c release and caspase-3 activation. It simultaneously suppresses the PI3K/Akt/mTOR survival signaling cascade, shifting the Bcl-2/Bax ratio toward pro-apoptotic signaling and committing cells to programmed cell death.

### Is tephrosin the same as rotenone?

Tephrosin and rotenone are both rotenoids that inhibit mitochondrial Complex I, but they are distinct chemical compounds with different molecular structures and potency profiles. Rotenone (C23H22O6) is more extensively studied and carries well-documented neurotoxicity risks in animals, while tephrosin (C23H22O7) has an additional hydroxyl group and a somewhat different selectivity profile, though its full toxicological characterization in mammals remains incomplete.

### Are there any tephrosin supplements available to buy?

Tephrosin is not currently available as a standardized, commercially marketed dietary supplement due to its status as a research-stage compound with no established human dosing, safety profile, or regulatory approval. It may appear as a raw research chemical from specialty chemical suppliers, but purchasing or consuming such products for self-supplementation is not supported by evidence and carries unknown safety risks given its mitochondrial toxicity mechanism.

### What does the current research evidence show about tephrosin's effectiveness in humans?

Most research on tephrosin has been conducted in laboratory and animal models, with studies showing promise in pancreatic, ovarian, and lung cancer cell lines and mouse xenografts. To date, there are no published clinical trials in human patients evaluating tephrosin's safety or efficacy, meaning claims about human benefits remain theoretical and unproven. The gap between preclinical results and human clinical data is substantial, and supplementation decisions should not be based on animal study outcomes alone.

### Who should avoid taking tephrosin supplements, and are there specific health conditions that contraindicate use?

Because tephrosin has not been clinically tested in humans, it should be avoided by pregnant women, nursing mothers, and children due to unknown safety risks. Individuals with liver disease, kidney disorders, or those taking chemotherapy drugs should exercise particular caution, as tephrosin's mechanisms of action may interact negatively with these conditions or treatments. Anyone with a family history of rotenone sensitivity should consult a healthcare provider before considering tephrosin, given the structural similarities between these compounds.

### How does tephrosin's mechanism differ from other natural compounds used in cancer research?

Tephrosin appears to work through multiple pathways including ROS (reactive oxygen species) generation, Hsp90 inhibition, and induction of autophagy—a multi-target approach that distinguishes it from single-mechanism compounds. Unlike some natural compounds that rely solely on apoptosis induction, tephrosin can restore chemotherapy sensitivity in drug-resistant cancer cells, suggesting a synergistic potential rather than standalone activity. This multi-pathway mechanism makes direct comparisons with other botanical extracts difficult and highlights why additional research is needed to understand its full biological effects.

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*Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com*
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