The first Ranatuerin antimicrobial peptide with LPS-neutralizing and anti-inflammatory activities in vitro and in vivo

Shibai Xiao; Maolin Tian; Hang Liao; Jianpeng Xie; Jinwei Chai; Jinqiao Li; Tienthanh Nguyen; Jiena Wu; Yihan Gao; Jiali Li; Xin Chen; Xueqing Xu; Wang Qingwen

doi:10.1016/j.lfs.2025.123375

The first Ranatuerin antimicrobial peptide with LPS-neutralizing and anti-inflammatory activities in vitro and in vivo

Life Sci. 2025 Jan 7:123375. doi: 10.1016/j.lfs.2025.123375. Online ahead of print.

Authors

Shibai Xiao¹, Maolin Tian², Hang Liao², Jianpeng Xie³, Jinwei Chai⁴, Jinqiao Li², Tienthanh Nguyen², Jiena Wu², Yihan Gao³, Jiali Li², Xin Chen³, Xueqing Xu⁵, Wang Qingwen⁶

Affiliations

¹ Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen 518036, China; Shenzhen Institute of Advanced Technology/Chinese Academy of Sciences (SIAT/CAS), Shenzhen, China.
² Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
³ Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
⁴ Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China. Electronic address: [email protected].
⁵ Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
⁶ Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen 518036, China. Electronic address: [email protected].

PMID: 39788417
DOI: 10.1016/j.lfs.2025.123375

Abstract

Pelophylax nigromaculata, common traditional Chinese medicinal material used for several hundreds of years, is one of the most widely distributed amphibians in China. In this study, a novel Ranatuerin-2 family antimicrobial peptide, Rana-2PN, was identified and characterized from its skin, and its structural characteristics and functional activities were studied extensively. First, Rana-2PN exhibited a broad spectrum of antimicrobial activity, displaying minimum inhibitory concentration (MIC) values ranging from 12.5 to 100 μM against all strains tested. Mechanistically, Rana-2PN exerted its bacteriostatic effects by binding to bacterial cells and inducing bacterial membrane rupture and subsequent bacterial death. Secondly, Rana-2PN effectively inhibited the inflammatory response in RAW264.7 cells induced by lipopolysaccharide (LPS) and reduced inflammation induced by carrageenan in mouse toes. Thus, Rana-2PN with LPS-neutralizing, anti-inflammatory, and antimicrobial properties, represents the first member of the Ranatuerin antimicrobial peptide family, and its discovery offers a promising therapeutic candidate for addressing inflammatory disorders resulting from bacterial infections.

Keywords: Anti-inflammation; Antimicrobial peptide; LPS; Ranatuerin-2; pelophylax nigromaculata.