Osthole ameliorates myonecrosis caused by Clostridium perfringens type A infection in mice

This study aimed to investigate the protective effect of the nature product osthole (OST) against Clostridium perfringens type A infection-caused myonecrosis in a mouse model. Male mice were divided into (1) control, (2) infected, (3) OST50 and (4) OST100 treatment groups. In the infected groups, mice were intramuscularly injected with 1 × 10 8 CFU of C. perfringens per day for 6 days. Mice in the OST50 and OST100 groups were administrated intraperitoneally with OST at the doses of 50 or 100 mg/kg per day post C. perfringens infection. Our results showed that C. perfringens infection caused marked necrosis and inflammatory cell infiltration in the muscle tissues of mice. Mice in the OST50 and OST100 treatment groups displayed significantly attenuated C. perfringens infection-induced lipid peroxidation, oxidative stress, and apoptosis in their muscle tissue. Furthermore, OST treatment significantly downregulated the expressions of NF-κB, IL-1β, and TNF-α mRNA and protein levels, while concomitantly upregulating the expressions of Nrf2 and HO-1 mRNA and protein. OST treatments also inhibited the expression of phosphorylation (p)-p38, p-mTOR, and p-Erk1/2 proteins, and upregulated LC3II and Beclin1 proteins. In summary, our results reveal that OST therapy confers a protective effect against C. perfringens infection-induced oxidative stress and inflammation in muscle tissue, via activation of Nrf2/HO-1 and autophagy pathways and inhibition of p38, Erk1/2 and NF-κB pathways.