Oxymatrine improves L-arginine-induced acute pancreatitis related intestinal injury via regulating AKT/NFkB and claudins signaling
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Oxymatrine (OMT) plays a significant role in chemical agents induced intestinal injury. However, its functional role in L-arginine (Arg) induced acute pancreatitis (AP) following intestinal injury and the corresponding molecular mechanism are unclear to our knowledge. We investigate OMT function in Arg induced AP following intestinal injury in vivo and vitro. OMT (4 mg/ml) decreased Arg (from 100 to 600 µM) induced IEC-6 cells growth in dose-dependent manner and inhibited Arg induced the increase of pAKT, bcl2, and the decrease of Bax. Meanwhile, OMT inhibited Arg (600 µM) induced the increase of pro-inflammatory cytokines TNF-a, IL-6, IL-1β, and NFkBp65 and the decrease of anti-inflammatory cytokine IL-10 expression. Moreover, the change of tight junction proteins claudins 1–4 expression induced by Arg was also reversed by OMT. Consistent with the results in vitro, OMT (50 mg/kg) inhibited Arg (250 mg/100 g) induced AP following intestinal injury in vivo. In detail, OMT resisted Arg induced inflammatory histology of both pancreas and intestine and inhibited Arg induced the change of pAKT, Bax, bcl2, TNF-a, IL-6, IL-1β, IL-10, NFkBp65, claudin 1–4 expression. Moreover, OMT inhibited Arg induced NFkBp65 and ICAM-1 expression in vivo by IHC. Oxymatrine improves Arg-induced acute pancreatitis following intestinal injury via inhibiting AKT/NFkB and claudins signaling.
KeywordsOxymatrine L-arginine Acute pancreatitis Intestinal injury Inflammation Claudins
We thank for the Central Laboratory and General Laboratory of the First Hospital of China Medical University for technical supports. This work was supported by Natural Science Foundation from Liaoning (20170540540) and by the science and technology program from Shenyang (population and health special project, 17-230-9-36).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- De Souza WF, Fortunato-Miranda N, Robbs BK, de Araujo WM, de-Freitas-Junior JC, Bastos LG (2013) Claudin-3 overexpression increases the malignant potential of colorectal cancer cells: roles of ERK1/2 and PI3K-Akt as modulators of EGFR signaling. PLoS One 8(9):e74994CrossRefPubMedPubMedCentralGoogle Scholar
- Gross CM, Kellner M, Wang T, Lu Q, Sun X, Zemskov EA, Noonepalle S, Kangath A, Kumar S, Gonzalez-Garay M, Desai AA, Aggarwal S, Gorshkov B, Klinger C, Verin AD, Catravas JD, Jacobson JR, Yuan JX, Rafikov R, Garcia JGN, Black SM (2017) LPS Induced Acute Lung Injury Involves the NF-κB-mediated Downregulation of SOX18. Am J Respir Cell Mol Biol 58(5):614–624CrossRefGoogle Scholar
- Hussain AR, Ahmed SO, Ahmed M, Khan OS, Al Abdulmohsen S, Platanias LC, Al-Kuraya KS, Uddin S (2012) Cross-talk between NFkB and the PI3-kinase/AKT pathway can be targeted in primary effusion lymphoma (PEL) cell lines for efficient apoptosis. PLoS One 7(6):e39945.CrossRefPubMedPubMedCentralGoogle Scholar
- Meriläinen S, Mäkelä J, Koivukangas V, Jensen HA, Rimpiläinen E, Yannopoulos F, Mäkelä T, Alestalo K, Vakkala M, Koskenkari J, Ohtonen P, Koskela M, Lehenkari P, Karttunen T, Juvonen T (2012) Intestinal bacterial translocation and tight junction structure in acute porcine pancreatitis. Hepatogastroenterology 59(114):599–606PubMedGoogle Scholar
- Ma ZJ, Li Q, Wang JB, Zhao YL, Zhong YW, Bai YF, Wang RL, Li JY, Yang HY, Zeng LN, Pu SB, Liu FF, Xiao DK, Xia XH, Xiao XH (2013) Combining oxymatrine or matrine with lamivudine increased its antireplication effect against the hepatitis B virus in vitro. Evid Based Complement Alternat Med https://doi.org/10.1155/2013/186573 Google Scholar
- Oshima T, Miwa H, Joh T (2008) Changes in the expression of claudins in active ulcerative colitis. J Gastroenterol Hepatol https://doi.org/10.1111/j.1440-1746
- Visigalli R, Barilli A, Parolari A, Sala R, Rotoli BM, Bussolati O, Gazzola GC, Dall’Asta V (2010) Regulation of arginine transport and metabolism by protein kinase Calpha in endothelial cells: stimulation of CAT2 transporters and arginase activity. J Mol Cell Cardiol 49(2):260–267CrossRefPubMedGoogle Scholar