title: α7 Nicotinic Acetylcholine Receptor is a Novel Mediator of Sinomenine Anti-Inflammation Effect in Macrophages Stimulated by Lipopolysaccharide.
abstract: Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effects and has been used for rheumatoid arthritis treatment in China. This study aims to verify the hypothesis that SIN acts on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit the activation of macrophages stimulated by lipopolysaccharide. The prototypical α7nAChR antagonist α-bungarotoxin and mecamylamine attenuated the effect of SIN on tumor necrosis factor-α and interleukin-6 in RAW264.7 murine macrophage-like cells and primary peritoneal macrophages of mouse induced by lipopolysaccharide. With the knockdown of α7nAChR expression in RAW264.7 cells by small interfering RNA, the inhibitory effect of SIN on tumor necrosis factor-α and interleukin-6 was reversed. Sinomenine decreased p65 expression in nuclear and increased IκBα expression in cytoplasm, and these effects were reversed by the α7nAChR small interfering RNA as well. These results indicate that the anti-inflammatory effects of SIN on macrophages in vitro depend on α7nAChR.
authors.affiliation: *Department of Immunology, Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou; and †State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Yi
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Luo
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Xie
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Liu
authors.forename: Jun-Yue
authors.initials: JY
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.forename: Pei-Xun
authors.initials: PX
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002038:Bungarotoxins / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009019:Morphinans / Q000737:chemistry*; D000072000:NF-KappaB Inhibitor alpha; D000067996:RAW 264.7 Cells; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D002038:Bungarotoxins; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009019:Morphinans; C000606205:Nfkbia protein, mouse; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000072000:NF-KappaB Inhibitor alpha; C009271:sinomenine; D008464:Mecamylamine