Salvinorin A protects against methicillin resistant staphylococcus aureus-induced acute lung injury via Nrf2 pathway

Abstract Salvinorin A (SA), a neoclerodane diterpene, is isolated from the dried leaves of Salvia divinorum. SA has traditionally been used treatments for chronic pain diseases. Recent research has demonstrated that SA possesses the anti-inflammatory property. The present study aim to explore the effects and potential mechanisms of SA in protection against Methicillin Resistant Staphylococcus aureus (MRSA)-induced acute lung injury (ALI). Here, we firstly found that very low doses of SA (50 μg/kg) could markedly decrease the infiltration of pulmonary neutrophils, mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and then attenuated ALI cause by MRSA infection in mice. In vitro findings revealed that SA attenuated lipoteichoic acid-induced apoptosis, inflammation and oxidative stress in RAW264.7 cells. Mechanism research revealed that SA increased both mRNA levels and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulated mRNA expression of its downstream genes (HO-1, Gclm, Trx-1, SOD1 and SOD2). Additionally, Nrf2 knockout mice abolished the inhibitory effect of SA on neutrophil accumulation and oxidative stress in MRSA-induced ALI. In conclusion, SA attenuates MRSA-induced ALI via Nrf2 signaling pathways.