Ginsenoside Rg1 Attenuates Lipopolysaccharide-Induced Inflammatory Responses Via the Phospholipase C-γ1 Signaling Pathway in Murine BV-2 Microglial Cells
作者:Y. Zong, Qinglin Ai, Lei Zhong, Jian Dai, Ping Yang, Yongwen He, Jiping Sun, Eng‐Ang Ling, Di Lü · 发表于:Current Medicinal Chemistry · 年份:2012 · DOI:10.2174/092986712798992066 · 被引用次数:51 · 研究领域:Ginseng Biological Effects and Applications、Neuroinflammation and Neurodegeneration Mechanisms、Tryptophan and brain disorders
Background and Purpose: Microglial activation plays an important role in neurodegenerative diseases by producing an array of proinflammatory enzymes and cytokines. Ginsenoside Rg1 (Rg1), a well-known Chinese herbal medicine, has been well recognized for its anti-inflammatory effect. This study sought to determine the anti-inflammatory effects of Rg1and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated murine BV-2 microglial cells. Experimental Approach: Murine BV-2 microglial cells were treated with Rg1 (10, 20, and 40 μM) and/or LPS (1 μg·ml-1). The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR assay and double immunofluorescence labeling, respectively. Phosphorylation levels of mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP- responsive element (CRE)-binding protein (CREB) were measured by western blot. U73122 (5 μM), a specific phospholipase C (PLC) inhibitor, was used to determine if PLC signaling pathway might be involved in Rg1s action on activated BV-2 cells. Key Results: Pretreatment with Rg1 significantly attenuated the LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor-κB (NF-κB) in BV-2 cells. U73122 blocked the effects of Rg1 on LPS-induced microglial activation. In addition, PLC-γ1 inhibition partially abolished the inhibitory effect of Rg1 on the ph...