title: Ilexgenin A, a novel pentacyclic triterpenoid extracted from Aquifoliaceae shows reduction of LPS-induced peritonitis in mice.
abstract: Ilexgenin A (IA) is a novel pentacyclic triterpenoid, which extracted from leaves of Ilex hainanensis Merr. In the present study, we aim to explore anti-inflammatory activity of IA on LPS-induced peritonitis and its underlying molecular mechanism. The results determined that IA was capable of suppressing peritonitis in mice induced by intraperitoneal (i.p.) injection of lipopolysaccaride (LPS). Furthermore, the results showed that IA dramatically inhibited levels of inflammatory cells infiltration in peritoneal cavity and serum in LPS-induced mice peritonitis model. Besides, IA could dramatically inhibit levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) in peritoneal cavity in LPS-induced mice peritonitis model. In vitro study, the results showed that IA inhibited production of IL-1β, IL-6 and TNF-α at transcriptional and translational levels in RAW 264.7 cells induced by LPS. Furthermore, IA could suppress the LPS-induced activation of Akt and downstream degradation and phosphorylation of kappa B-α (IκB-α). Moreover, IA could significantly inhibit ERK 1/2 phosphorylation in RAW 264.7 cells induced by LPS. These results were concurrent with molecular docking which revealed ERK1/2 inhibition. These results demonstrated that IA might as an anti-inflammatory agent candidate for inflammatory disease therapy.
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China; Chinese Medicine Hospital of Yangzhou City, Yangzhou 225009, Jiangsu, PR China; Nanjing University of Chinese Medicine, Nanjing 210009, PR China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Sun
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China; Pharmacy of School, University of Missouri-Kansas City, MO 64108, United States.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China; Jiangsu Hengrui Medicine Co.,ltd, Kunshan 222047, Jiangsu, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Pharmacy of School, University of Missouri-Kansas City, MO 64108, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Nanjing University of Chinese Medicine, Nanjing 210009, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Rong
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, Yangzhou 225001, Jiangsu, PR China. Electronic address: ysun@yzu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D029063:Aquifoliaceae / Q000737:chemistry*; D020134:Catalytic Domain; D002452:Cell Count; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000378:metabolism; D010529:Peritoneal Cavity; D010538:Peritonitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000067996:RAW 264.7 Cells; D014315:Triterpenes / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C468850:ilexgenin A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Anti-inflammation; Aquifoliaceae; Ilexgenin A; Lipopolysaccaride; Pentacyclic triterpenoid; Peritonitis