Tanshinone IIA reduces lethality and acute lung injury in LPS-treated mice by inhibition of PLA2 activity.
Tanshinone IIA (TIIA) is one of the main active components from Chinese herb danshen. Previous reports showed that TIIA reduced the production of pro-inflammatory mediators stimulated with lipopolysaccharide (LPS). However, the effects of TIIA on LPS-induced acute lung injury are not fully understood. Here, we observed the effects of TIIA on mortality and lung injury in LPS-treated mice and on LPS-induced pulmonary epithelial cell injury, and further studied the underlying mechanism. As revealed by survival study, pretreatment with TIIA reduced mortality of mice and prolonged their survival time. Meanwhile, TIIA pretreatment significantly improved LPS-induced lung histopathologic changes, decreased lung wet-to-dry and lung-to-body weight ratios, inhibited lung myeloperoxidase activity and reduced protein leakage. TIIA also alleviated LPS-induced pulmonary epithelial cell injury, as proved by methyl thiazolyl tetrazolium (MTT) and lactic dehydrogenase assay. Furthermore, TIIA suppressed LPS-induced phospholipase A2 (PLA2) activity in both lung homogenate and bronchoalveolar lavage fluid. TIIA also inhibited the metabolites of PLA2, which was confirmed by results of thromboxane B2, prostaglandin E2 and leukotriene B4 detection. Besides, TIIA in vitro inhibited LPS-induced PLA2 activity in a dose-dependent manner. Western blotting showed that TIIA markedly inhibited the activation of nuclear factor kappa B (NF-kappaB) in LPS-treated mice. Taken together, these data firstly provided the novel information that the protective role of TIIA against LPS-induced lung injury may attribute partly to the inhibition of PLA2 activity and NF-kappaB activation.
Xu
Min
M
Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, PR China.
Dong
Ming-Qing
MQ
Cao
Fa-Le
FL
Liu
Man-Ling
ML
Wang
Yan-Xia
YX
Dong
Hai-Ying
HY
Huang
Yu-Fang
YF
Liu
Yi
Y
Wang
Xiao-Bin
XB
Zhang
Bo
B
Zhao
Peng-Tao
PT
Luo
Ying
Y
Niu
Wen
W
Cui
Yan
Y
Li
Zhi-Chao
ZC