# PS77: a novel peptide with α-helical structure for targeted anti-inflammatory therapy in biomaterials design

## TL;DR

This paper introduces PS77, a new anti-inflammatory peptide from traditional medicine, showing it can reduce inflammation without harming cells, offering potential for better biomaterials in treating inflammatory diseases.

## Contribution

The paper introduces PS77, a novel α-helical peptide with anti-inflammatory properties for use in biomaterials design.

## Key findings

- PS77 significantly reduced IL-8 and MMP-3 expression in an in vitro inflammatory model without cytotoxicity.
- Transcriptomic analysis showed PS77 modulated 265 genes, particularly downregulating BMP and TGF-β signaling pathways.
- PS77 regulated multiple inflammation-associated genes, including CHRNA7, CXCR5, and RXRG.

## Abstract

Chronic inflammation underlies many diseases, posing challenges in therapeutic management due to the limitations and side effects of current treatments and necessitating novel therapeutic solutions. Here, we introduce PS77, a novel α-helical peptide derived from Squama Manitis, a Traditional Chinese Medicine, and unveil its remarkable anti-inflammatory properties, potentially revolutionizing biomaterials design for targeted anti-inflammatory therapies. An in vitro TNF-α-induced inflammatory model in human keratinocytes (HaCaT cells) was used to demonstrate PS77’s significant impact. We demonstrated that PS77 significantly reduced IL-8 and MMP-3 expression, indicating potent anti-inflammatory activity without cytotoxicity to normal cells. Transcriptomic analysis further elucidated PS77’s mechanism of action, revealing significant modulation of 265 genes (137 upregulated and 128 downregulated), with a particular focus on the downregulation of genes within the BMP and TGF-β signaling pathways—key players in inflammation. Moreover, PS77 regulated several inflammation-associated genes, including CHRNA7, CXCR5, RXRG, KRT76, IL12RB2, and COLEC11, underscoring its comprehensive anti-inflammatory effects. This study not only highlights PS77’s therapeutic potential as a biomaterial for treating inflammatory diseases but also paves the way for further research into its mechanisms and applications in biomedicine. By leveraging the novel biomaterial properties of PS77, this research may contribute to the development of targeted and efficient anti-inflammatory therapies, marking a significant advance in the field of biomaterials and offering a promising avenue for inflammation management.

The online version contains supplementary material available at 10.1007/s12026-025-09663-0.