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

Si Zeng, Dan Chen, Gang Liu, Ya-Xian Wu, Zhi-Qi Gao, Ying Su, Jia-Ning Yuan, Liu Liu, Jia-Chen Shan, Qing-Feng Pang, Tao Zhu

International immunopharmacology 2021 Jan

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Salvinorin A (SA), a neoclerodane diterpene, is isolated from the dried leaves ofSalvia 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 potentialmechanisms ofSA in protection against Methicillin Resistant Staphylococcus aureus (MRSA)-induced acute lung injury (ALI). Here, we firstly found that verylowdosesof 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 lipoteichoicacid-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. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Si Zeng, Dan Chen, Gang Liu, Ya-Xian Wu, Zhi-Qi Gao, Ying Su, Jia-Ning Yuan, Liu Liu, Jia-Chen Shan, Qing-Feng Pang, Tao Zhu. Salvinorin A protects against methicillin resistant staphylococcus aureus-induced acute lung injury via Nrf2 pathway. International immunopharmacology. 2021 Jan;90:107221