title: Astragaloside IV suppresses inflammatory mediator production in synoviocytes and collagen‑induced arthritic rats.
abstract: The aim of the current study was to investigate the effects of Astragaloside‑IV (AS‑IV) on inflammatory mediators in synoviocytes and collagen‑induced arthritic rats. Synoviocytes were stimulated with lipopolysaccharides (LPS) and Sprague‑Dawley rats were injected with type II collagen. AS‑IV was administered to the LPS‑stimulated synoviocytes and collagen‑induced arthritis (CIA) rats. The inflammation of LPS‑stimulated synoviocytes and CIA rats was assessed using enzyme‑linked immunosorbent assays and western blotting. Using Cell Counting Kit‑8 analysis, it was demonstrated that AS‑IV (5, 20 and 50 mg/ml) inhibited the LPS‑stimulated synoviocytes proliferation in a dose‑dependent manner. AS‑IV significantly inhibited the LPS‑stimulated inflammatory response, as indicated by the expression levels of TNF‑α, IL‑1β, IL‑6 and IL‑8. In addition, treatment with AS‑IV significantly reduced the LPS‑stimulated cyclooxygenase (COX)‑1, COX‑2, high mobility group box 1 protein (HMGB1) and intercellular adhesion molecule 1 overexpression, and intranuclear nuclear factor (NF)‑κBp65 subunit accumulation and activation of c‑Jun N‑terminal kinase (JNK)1/2 and p38. Similar to the protective effects of AS‑IV on LPS‑stimulated synoviocytes, AS‑IV treatment significantly reduced the expression levels of tumor necrosis factor α, interleukin (IL)‑1β, IL‑6 and IL‑8 expression levels, and attenuated intranuclear NF‑κBp65 subunit accumulation and overexpression of COX‑2 and inducible nitric oxide synthase in CIA rats. In conclusion, the results of the present study demonstrated for the first time, to the best of our knowledge, that AS‑IV protects synoviocytes against LPS‑ and collagen‑induced inflammatory responses through inhibition of the HMGB1‑dependent JNK1/2‑ and p38‑activated NF‑κB/COX‑2 pathway.
authors.affiliation: Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China.
authors.forename: Chang-Yao
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China.
authors.forename: Hai-Ning
authors.initials: HN
authors.lastname: Zhang
authors.affiliation: Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Lv
authors.affiliation: Joint Department of Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong 266100, P.R. China.
authors.forename: Ying-Zhen
authors.initials: YZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024043:Collagen Type II / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000032:analysis; D015536:Down-Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D000070918:Synoviocytes / Q000166:cytology / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D024043:Collagen Type II; D016207:Cytokines; D024243:HMGB1 Protein; C573420:ICAM1 protein, human; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; D018799:Intercellular Adhesion Molecule-1; C052064:astragaloside A; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D048031:JNK Mitogen-Activated Protein Kinases