title: Astragaloside IV ameliorates acute pancreatitis in rats by inhibiting the activation of nuclear factor-κB.
abstract: This study aimed to investigate the effects of astragaloside IV (AS-IV; 3-O-β-D-xylopyranosyl-6-O‑β-D-glucopyranosylcycloastragenol), which has been reported to have comprehensive pharmacological functions, on sodium taurocholate (NaTc)/L-arginine (L-Arg)-induced acute pancreatitis (AP) in rats in vivo and in rat pancreatic acinar cells in vitro. NaTc-induced experimental AP was induced in rats by injecting 4% NaTc (0.1 ml/100 g) in the retrograde direction of the biliopancreatic duct. L-Arg-induced experimental AP was induced in rats by 2 intraperitoneal injections of 20% L-arg (3 g/kg), with an interval of 1 h between the injections. The rats were pre-treated AS-IV (50 mg/kg) or the vehicle (DMSO) 2 h prior to the induction of AP. Enzyme-linked immunosorbent assay, H&E staining, myeloperoxidase (MPO) activity, reverse transcription-quantitative PCR, western blot analysis and immunohistochemistry were used to evaluate the effects of AS-IV on AP. The results revealed that treatment with AS-IV significantly reduced serum amylase and lipase levels, pancreatic pathological alterations, the secretion of pro-inflammatory cytokines, MPO activity, and the protein expression of nuclear factor-κB (NF-κB) in vivo. Moreover, pre-treatment with AS-IV significantly increased the expression levels of manganese superoxide dismutase and cuprum/zinc superoxide dismutase. In the in vitro experiment, treatment of the cells with AS-IV aslo reduced rat pancreatic acinar cell necrosis and nuclear NF-κB activity, and enhanced the protein expression of superoxide dismutase. In conclusion, this study indicates that the protective effects of AS-IV on experimental AP in rats may be closely related to the inhibition of NF-κB. In addition, our results indicate that AS-IV may exert potential antioxidant effects on AP. Therefore, AS-IV may be an effective therapeutic agent for AP.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Guojian
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai 200080, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Wenqin
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai 200080, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai 200080, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Xing
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Jia
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai 200080, P.R. China.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai 200080, P.R. China.
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Maochun
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009336:Necrosis; D010195:Pancreatitis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D009195:Peroxidase; D008049:Lipase; D000681:Amylases