Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling

Pharmaceutical Biology

Tian Sun¹  Qingliang Shao²  Zhiqiang Zhang²  Hui Zang²  Qingfeng Liu² 

[1] Department of General Surgery, The People's Hospital of China Medical University, Shenyang, Chin;Department of General Surgery, The People's Hospital of Liaoning Province, Shenyang, China;

关键词: Intestinal barrier;    inflammation;    IL17;    ROR-γt;    T-bet;    ERK;    P38;   

DOI  :  10.1080/13880209.2019.1657906

来源: Taylor & Francis

【 摘 要 】

Context: Oxymatrine (OMT) has various pharmacological effects, including immune reaction regulation, anti-inflammation and anti-hypersensitive reaction.Objective: This is the first report to investigate the molecular mechanism of OMT function in l-arginine (Arg)-induced acute pancreatitis (AP) involving intestinal injury.Materials and methods: Rat pancreatic AR42J and small intestinal IEC-6 cells were treated with Arg (200–800 µM) for 48 h plus OMT (4 mg/mL) treatment. Thirty adult Wistar rats were randomly assigned to control (saline), AP (i.p. of 250 mg/100 g body weight Arg) and OMT (i.p. injection of 50 mg/kg b.w. OMT every 6 h following Arg). Both cells and rats were harvested at 48 h.Results: Arg-induced cell proliferation in both rats AR42J (EC50 633.9 ± 31.4 µM) and IEC-6 cells (EC50 571.3 ± 40.4 µM) in a dose-dependent manner, which was significantly inhibited by OMT (4 mg/mL). Meanwhile, Arg (600 µM) induced expression of proinflammatory cytokines (TNF-α, IL-6, IL-1β, NF-κB, IL-17A/IL-17F and IFN-γ) and activation of p-p38/p-ERK in vitro, which was reversed by OMT. In vivo, OMT (50 mg/kg) inhibited 250 mg/100 g of Arg-induced AP involving intestinal injury, including inhibiting Arg-induced inflammatory in pancreas and intestine, inhibiting Arg-induced increase of TNF-α, IL-6, IL-1β, NF-κB and p-p38/p-ERK-MAPK signalling, and inhibiting Arg-induced increase of IL-17A/IL-17F, IFN-γ, ROR-γt and T-bet. Meanwhile, OMT inhibited Arg-induced expression of CD44 and CD55 in intestinal injury.Discussion and conclusions: OMT protects against Arg-induced AP involving intestinal injury via regulating Th1/Th17 cytokines and MAPK/NF-κB signalling, which is a promising therapeutic agent in clinics.

【 授权许可】

CC BY