title: Liang-Ge-San, a classic traditional Chinese medicine formula, protects against lipopolysaccharide-induced inflammation through cholinergic anti-inflammatory pathway.
abstract: Liang-Ge-San (LGS) is a classic formula in traditional Chinese medicine, which is widely used to treat acute lung injury (ALI), pharyngitis and amygdalitis in clinic. However, the underlying mechanisms remain poorly defined. In this study, we discovered that LGS exerted potent anti-inflammatory effects in lipopolysaccharide (LPS)-induced inflammation. We found that LGS significantly depressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophage cells. The degradation and phosphorylation of IκBα and the nuclear translocation of NF-κB p65 were also inhibited. Moreover, LGS activated α7 nicotinic cholinergic receptor (α7nAchR). The blockage of α7nAchR by selective inhibitor methyllycaconitine (MLA) or α7nAchR siRNA attenuated the inhibitory effects of LGS on IκBα, NF-κB p65, IL-6 and TNF-α. Critically, LGS significantly inhibited inflammation in LPS-induced ALI rats through the activation of NF-κB signaling pathway. However, these protective effects could be counteracted by the treatment of MLA. Taken together, we first demonstrated anti-inflammatory effects of LGS both in vitro and in vivo through cholinergic anti-inflammatory pathway. The study provides a rationale for the clinical application of LGS as an anti-inflammatory agent and supports the critical role of cholinergic anti-inflammatory pathway in inflammation.
authors.affiliation: Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Jun-Shan
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Xi-Duan
authors.initials: XD
authors.lastname: Wei
authors.affiliation: Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Zi-Bin
authors.initials: ZB
authors.lastname: Lu
authors.affiliation: Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Zhou
authors.affiliation: Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Yu-Yao
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Jia-Mei
authors.initials: JM
authors.lastname: Ma
authors.affiliation: Department of Traditional Chinese Medicine, Southern Medical University, Guangzhou, P. R. China.
authors.forename: Lin-Zhong
authors.initials: LZ
authors.lastname: Yu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018678:Cholinergic Agents / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D018678:Cholinergic Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides
keywords: Immune response; Immunity; Immunology and Microbiology Section; Liang-Ge-San; NF-κB; inflammation; α7 nicotinic cholinergic receptor