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

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 mu M 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.