标题：Anti-inflammatory Effect of Acetylpuerarin on Eicosanoid Signaling Pathway in Primary Rat Astrocytes
作者：Xiang, Yanxiao; Wei, Xinbing; Chen, Lin; Liu, Huiqing; Liu, Xiaoqian; Wang, Tian; Zhang, Xiumei
作者机构：[Xiang, Yanxiao; Wei, Xinbing; Chen, Lin; Liu, Huiqing; Liu, Xiaoqian; Zhang, Xiumei] Shandong Univ, Sch Med, Dept Pharmacol, Jinan 250012, Shandong, 更多
通讯作者地址：[Zhang, XM]Shandong Univ, Sch Med, Dept Pharmacol, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源：JOURNAL OF MOLECULAR NEUROSCIENCE
关键词：Acetylpuerarin; Inflammation; Rat astrocytes in primary culture;; Eicosanoid; GroupV sPLA(2); COX and LOX
摘要：Astrocytes activation has been implicated in the inflammatory responses underlying brain injury and neurodegenerative diseases including bacterial infections, cerebral ischemia, and Parkinson's diseases. Acetylpuerarin is a newly modified isoflavone based on puerarin that has neuroprotective and antioxidant effects. In this study, we investigated the anti-inflammatory action of acetylpuerarin in regulating the eicosanoids generation and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced production of arachidonic acid (AA) metabolites in primary rat astrocytes. The results showed that acetylpuerarin concentration dependently inhibited the LPS-induced production of AA metabolites such as prostaglandin E-2 (PGE(2)) and leukotriene C-4 (LTC4), and acetylpuerarin significantly attenuated the expression and immunoreactivity of group V secretory phospholipase A(2) (sPLA(2)) protein induced by LPS in astrocytes. Furthermore, in astrocytes pretreated with acetylpuerarin, the time course of phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and of cytosolic PLA(2) alpha (cPLA(2)alpha) and expression of transcription factors, nuclear factor kappa B (NF-kappa B), was markedly truncated. Acetylpuerarin concentration dependently abolished the LPS-induced expressions of AA-metabolizing enzymes including cyclooxygenase-2 (COX-2) and lipooxygenase-5 (LOX-5). This study indicates that acetylpuerarin inhibited LPS-induced AA-metabolizing enzymes and AA metabolites in astrocytes via downregulation expression of group V sPLA(2) and phosphorylation of ERK1/2, cPLA(2)alpha, and NF-kappa B. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of acetylpuerarin.