# Tripterygium glycosides: recent advances in mechanisms, therapeutic applications, and safety optimization

## TL;DR

This review explores recent progress in understanding and improving tripterygium glycosides, natural compounds with anti-inflammatory properties used for autoimmune and inflammatory diseases.

## Contribution

The paper highlights new strategies to reduce toxicity and enhance efficacy of tripterygium glycosides through structural optimization and innovative drug delivery.

## Key findings

- Tripterygium glycosides show therapeutic potential in autoimmune and inflammatory diseases like lupus and rheumatoid arthritis.
- New derivatives like LLDT-8 and triptonide reduce toxicity while maintaining efficacy.
- Advanced techniques like AI-assisted drug design are accelerating the development of safer TG-based therapeutics.

## Abstract

Tripterygium glycosides (TG), bioactive extracts derived from Tripterygium wilfordii Hook F., possess potent anti-inflammatory and immunomodulatory properties, making them promising therapeutic candidates for a range of autoimmune and inflammatory diseases. This review summarizes recent advances in the pharmacological mechanisms of TG, including their roles in cytokine suppression, autophagy modulation, anti-fibrotic remodeling, and oxidative stress regulation. Evidence from clinical trials and real-world studies supports the therapeutic potential of TG in conditions such as systemic lupus erythematosus, diabetic kidney disease, rheumatoid arthritis, and psoriasis. In addition, we highlight ongoing efforts to overcome TG's narrow therapeutic window through monomer isolation, structural optimization, prodrug strategies, and innovative delivery systems. Emerging derivatives—such as LLDT-8 (5R-5-hydroxytriptolide) and triptonide—exhibit reduced toxicity while retaining robust efficacy, providing new avenues for clinical translation. Furthermore, the integration of systems pharmacology, synthetic biology, and AI-assisted drug design is accelerating the development of next-generation TG-based therapeutics.