Daphnetin alleviates lipopolysaccharide/D-galactosamine-induced acute Cheek for liver failure via the inhibition of NLRP3, MAPK and NF-κB, and the induction of autophagy
Daphnetin alleviates lipopolysaccharide/D-galactosamine-induced acute Cheek for liver failure via the inhibition of NLRP3, MAPK and NF-κB, and the induction of autophagy
复制标题
Daphnetin 通过抑制 NLRP3、MAPK 和 NF-κB 以及诱导自噬来减轻脂多糖/d-半乳糖胺诱导的急性肝衰竭
DOI：
10.1016/j.ijbiomac.2018.07.101
复制
发表时间：
2018-11-01
影响因子：
8.2
通讯作者：
Ci, Xinxin
中科院分区：
文献类型：
--
作者：
Lv, Hongming;Fan, Xiaoye;Ci, Xinxin
Acute liver failure (ALF), an inflammation-mediated hepatocellular injury process, is a life-threatening and fatal clinical syndrome. Daphnetin (Daph) has been reported to exhibit various pharmacological activities, particularly its antiinflammatory property. The present study was designed to evaluate the protective effects and underlying mechanisms of Daph against lipopolysaccharide and D-galactosamine (LPS/GaIN)-induced ALF in mice. Our findings suggested that Daph treatment efficiently protected against LPS/GaIN-induced ALF by lessening the lethality, decreasing the alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 secretion, malondialdehyde (MDA) formation and myeloperoxidase (MPO) level, inhibiting nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein expression, and increasing the glutathione (GSH) and superoxide dismutase (SOD) contents. Moreover, Daph treatment effectively inhibited LPS/GaIN-induced nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), mitogenactivated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappa B) signaling pathway activation, and significantly induced autophagy activation by enhancing the level of pro-autophagy proteins expression. Taken together, these findings suggested that Daph plays a pivotal role in liver protection by suppressing inflammatory responses which may be closely associated with the inhibition of NLRP3 inflammasome, MAPK and NF-kappa B activation, as well as the induction of autophagy. (C) 2018 Published by Elsevier B.V.
