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

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) invo...

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Autores principales:	Zhiqiang Zhang, Qingfeng Liu, Hui Zang, Qingliang Shao, Tian Sun
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	intestinal barrier inflammation il17 ror-γt t-bet erk p38 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/42419b160b2c4d1eadcfc0eadbfdf813
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spelling	oai:doaj.org-article:42419b160b2c4d1eadcfc0eadbfdf8132021-11-17T14:21:56ZOxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling1388-02091744-511610.1080/13880209.2019.1657906https://doaj.org/article/42419b160b2c4d1eadcfc0eadbfdf8132019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1657906https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: 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.Zhiqiang ZhangQingfeng LiuHui ZangQingliang ShaoTian SunTaylor & Francis Grouparticleintestinal barrierinflammationil17ror-γtt-beterkp38Therapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 595-603 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	intestinal barrier inflammation il17 ror-γt t-bet erk p38 Therapeutics. Pharmacology RM1-950
spellingShingle	intestinal barrier inflammation il17 ror-γt t-bet erk p38 Therapeutics. Pharmacology RM1-950 Zhiqiang Zhang Qingfeng Liu Hui Zang Qingliang Shao Tian Sun Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling
description	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.
format	article
author	Zhiqiang Zhang Qingfeng Liu Hui Zang Qingliang Shao Tian Sun
author_facet	Zhiqiang Zhang Qingfeng Liu Hui Zang Qingliang Shao Tian Sun
author_sort	Zhiqiang Zhang
title	Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling
title_short	Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling
title_full	Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling
title_fullStr	Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling
title_full_unstemmed	Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling
title_sort	oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving th1/th17 cytokines and mapk/nf-κb signalling
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/42419b160b2c4d1eadcfc0eadbfdf813
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Oxymatrine protects against l-arginine-induced acute pancreatitis and intestine injury involving Th1/Th17 cytokines and MAPK/NF-κB signalling

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