# Targeted ferroptosis of myofibroblasts by tubeimoside I attenuates hypertrophic scar formation

## TL;DR

This study shows that TBMS1 can reduce scar formation by causing cell death in scar-forming cells through a process called ferroptosis.

## Contribution

TBMS1 induces ferroptosis in myofibroblasts, offering a novel therapeutic strategy for hypertrophic scars.

## Key findings

- TBMS1 inhibits myofibroblast proliferation, migration, and activation in vitro.
- TBMS1 triggers ferroptosis via the PI3K/AKT pathway and alters NRF2, SLC40A1, and GPX4 expression.
- In vivo experiments show TBMS1 has antifibrotic effects, reducing scar formation.

## Abstract

Hypertrophic scar (HS), the skin fibroproliferative disease, occurs after burn injury, traumatic injury, and surgery, resulting in high medical and economic burdens. Tubeimoside-I (TBMS1), a triterpenoid saponin monomer obtained from the Chinese medicinal herb Tubeimu, has demonstrated therapeutic potential in various diseases. In the present study, we explored the therapeutic effect of TBMS1 in the progression of HS.

In vitro studies tested the effects of TBMS1 on the biological behaviors of hypertrophic scar fibroblasts (HSFs) were investigated by cell counting kit-8, flow cytometry, wound healing, transwell, and collagen gel contraction assays. Further, the regulatory mechanism of TBMS1 in alleviating HS was elucidated. In vivo experiments were utilized to reveal the influences of TBMS1 on HS formation.

In vitro studies indicated that TBMS1 hindered HSFs proliferation, migration, and myofibroblast activation. The PI3K/AKT signaling pathway mediates TBMS1-induced ferroptosis, which was accompanied by altered expression of NRF2, SLC40A1, and GPX4, ultimately suppressing cell proliferation and collagen synthesis. In vivo experiments confirmed that local TBMS1 injection exerted potent antifibrotic effects.

This study revealed the effect of TBMS1 in activating ferroptosis, suggesting that inducing ferroptosis is probably a novel therapeutic strategy for hypertrophic scar.