# Triptolide in renal disorders: dual roles of therapeutic potential and nephrotoxicity: a narrative review

## TL;DR

Triptolide can help treat kidney diseases but may also harm the kidneys at high doses, requiring careful study to maximize benefits and minimize risks.

## Contribution

This review systematically analyzes triptolide's dual therapeutic and toxic effects on the kidneys and proposes strategies to enhance its clinical utility.

## Key findings

- Therapeutic doses of triptolide protect podocytes and inhibit renal fibrosis in renal models.
- Nephrotoxicity occurs at higher doses through oxidative stress and direct damage to renal tubular cells.
- Strategies like targeted delivery systems and structural analogs may help separate triptolide's efficacy from toxicity.

## Abstract

Triptolide (TP), derived from Tripterygium wilfordii, exhibits anti-inflammatory, immunosuppressive, and antifibrotic properties with potential for treating renal diseases, but its clinical use is restricted by dose-dependent nephrotoxicity.

The aim of this review is to comprehensively summarize the dual roles of TP, elucidate its therapeutic mechanisms and nephrotoxic pathways, and to explore strategies to mitigate its toxicity.

A literature search was performed using the PubMed and Web of Science databases. The search covered publications from the earliest available date until November 2025. The key search terms included ‘triptolide’, ‘renal’, ‘kidney’ and their combinations.

TP exerts dose-dependent dual effects in renal models. Therapeutic doses (typically ≤200 μg/kg in vivo) demonstrate efficacy in modulating immune responses, protecting podocytes, promoting apoptosis in hyperproliferative cells and inhibiting renal fibrosis. Conversely, its nephrotoxicity manifests at supratherapeutic doses (often >400 μg/kg in vivo) through oxidative stress, inflammation, metabolic dysregulation, and direct damage to renal tubular cells. The therapeutic efficacy and toxicity of TP are critically contingent on both dose and temporal parameters.

TP holds significant but challenging potential for renal therapy. Future research should define its therapeutic window and advance strategies such as structural analogs, targeted delivery systems, and combination therapies to effectively separate efficacy from toxicity for clinical translation.