Zeng Si, Chen Dan, Liu Gang, Wu Ya-Xian, Gao Zhi-Qi, Su Ying, Yuan Jia-Ning, Liu Liu, Shan Jia-Chen, Pang Qing-Feng, Zhu Tao
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Anesthesiology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610000, China.
Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China.
Int Immunopharmacol. 2021 Jan;90:107221. doi: 10.1016/j.intimp.2020.107221. Epub 2020 Dec 3.
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.
Salvinorin A（SA）是一种新克罗烷二萜，从鼠尾草的干燥叶子中分离得到。传统上，SA被用于治疗慢性疼痛疾病。最近的研究表明，SA具有抗炎特性。本研究旨在探讨SA在预防耐甲氧西林金黄色葡萄球菌（MRSA）诱导的急性肺损伤（ALI）中的作用及潜在机制。在此，我们首先发现极低剂量的SA（50μg/kg）可显著减少肺中性粒细胞浸润、促炎细胞因子（TNF-α、IL-1β和IL-6）的mRNA表达，进而减轻MRSA感染引起的小鼠ALI。体外研究结果显示，SA可减轻脂磷壁酸诱导的RAW264.7细胞凋亡、炎症和氧化应激。机制研究表明，SA可增加核因子红细胞2相关因子2（Nrf2）的mRNA水平和蛋白水平，并上调其下游基因（HO-1、Gclm、Trx-1、SOD1和SOD2）的mRNA表达。此外，Nrf2基因敲除小鼠消除了SA对MRSA诱导的ALI中中性粒细胞积聚和氧化应激的抑制作用。总之，SA通过Nrf2信号通路减轻MRSA诱导的ALI。
