Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling
| العنوان: | Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling |
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| المؤلفون: | Zhiqiang Zhang, Hui Zang, Tian Sun, Qingliang Shao, Qingfeng Liu |
| المصدر: | Pharmaceutical Biology, Vol 57, Iss 1, Pp 595-603 (2019) Pharmaceutical Biology |
| بيانات النشر: | Taylor & Francis Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, MAPK/ERK pathway, Arginine, Anti-Inflammatory Agents, Pharmaceutical Science, Pharmacology, 030226 pharmacology & pharmacy, 01 natural sciences, chemistry.chemical_compound, 0302 clinical medicine, ror-γt, Drug Discovery, Th1 th17, Chemistry, NF-kappa B, t-bet, General Medicine, Oxymatrine, Acute Disease, Cytokines, Molecular Medicine, Acute pancreatitis, medicine.symptom, Quinolizines, Research Article, MAP Kinase Signaling System, Inflammation, p38, RM1-950, Cell Line, erk, 03 medical and health sciences, il17, Alkaloids, Ileum, medicine, Animals, Nf κb signalling, Rats, Wistar, Cell Proliferation, Th1 Cells, medicine.disease, 0104 chemical sciences, Disease Models, Animal, 010404 medicinal & biomolecular chemistry, intestinal barrier, Pancreatitis, Complementary and alternative medicine, inflammation, Intestine injury, Th17 Cells, Therapeutics. Pharmacology |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1744-5116 1388-0209 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::462645b565dca3ce135474ca094d7ccb https://doaj.org/article/42419b160b2c4d1eadcfc0eadbfdf813 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....462645b565dca3ce135474ca094d7ccb |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 17445116 13880209 |
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