# Network pharmacology and experiments verify the effect of triptolide on extraocular muscle fibrosis

## TL;DR

This study explores how triptolide may treat extraocular muscle fibrosis in Graves’ ophthalmopathy by targeting the PI3K/AKT pathway.

## Contribution

The study combines network pharmacology and experiments to reveal triptolide's antifibrotic mechanism in extraocular muscle fibrosis.

## Key findings

- Triptolide inhibits fibrosis-related markers like FN, CTGF, α-SMA, and TIMP-1 in a concentration-dependent manner.
- Triptolide shows strong molecular docking affinity with core targets on the PI3K/AKT pathway.
- PI3K/AKT pathway inhibition reduces fibrosis markers, suggesting its key role in triptolide's antifibrotic effect.

## Abstract

Drugs usually do not prevent extraocular muscle fibrosis in Graves’ ophthalmopathy (GO), and surgical treatment has complications and does not cure extraocular muscle fibrosis. Triptolide (TPL) has shown antifibrotic effects; however, the mechanism by which it treats extraocular muscle fibrosis in GO remains unclear. The aim of this study was to investigate the therapeutic effect and potential mechanism of TPL through a combination of network pharmacology and experimental validation. Network pharmacology identified 10 potential therapeutic targets, 1767 gene ontology terms, and 95 signaling pathways, including the PI3K/AKT pathway. Molecular docking revealed a strong affinity between core targets on the PI3K/AKT pathway and TPL. The experimental results showed that TPL inhibited the proliferation of OFs in vitro in a concentration-dependent manner. It significantly inhibited the expression of TGF-β1-induced fibrosis-related markers, such as FN, CTGF, α-SMA, and TIMP-1, while significantly down-regulating the expression of PI3K/AKT signaling proteins. The use of inhibitors of the PI3K/AKT pathway inhibited the expression of fibrosis-related markers. These findings suggest that TPL can resist extraocular muscle fibrosis in GO through multiple pathways, in which the PI3K/AKT pathway plays a key role.