Berberine Attenuates Myocardial Ischemia Reperfusion Injury by Suppressing the Activation of PI3K/AKT Signaling

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2016 Mar 22

PMID 26998023

Citations 23

Authors

Zhu Qin-Wei

L I Yong-Guang

Affiliations

Soon will be listed here.

Abstract

Berberine (BBR), an isoquinoline alkaloid originally isolated from the Chinese herb (Huanglian), exhibits anti-inflammatory and immunosuppressive properties. Since myocardial ischemia/reperfusion (I/R) injury is associated with an excessive immune response, the current study was conducted to investigate the impact of BBR on myocardial I/R injury, a common disorder in clinical settings. Preconditioning of Sprague-Dawley rats with BBR (100 mg/kg/day, by gavage) for 14 days prior to the induction of I/R significantly attenuated myocardial I/R injury as manifested by a reduction in the incidence of ventricular arrhythmia and the amelioration of myocardial histological changes. These effects were found to be associated with the suppression of the phosphoinositide 3-kinase/AKT signaling pathway and the subsequent reduction of the expression of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α in the serum and myocardial tissue. These results indicate that BBR has the potential be an effective alternative therapy for the prevention and treatment of myocardial I/R injury in clinical practice.

Citing Articles

Berberine Intervention Mitigates Myocardial Ischemia-Reperfusion Injury in a Rat Model: Mechanistic Insights via miR-184 Signaling.

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Research progress on pharmacological effects and bioavailability of berberine.

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References

Zhang S, Lv J, Yang P, Yu Q, Pang J, Wang Z . Loss of dicer exacerbates cyclophosphamide-induced bladder overactivity by enhancing purinergic signaling. Am J Pathol. 2012; 181(3):937-46. DOI: 10.1016/j.ajpath.2012.05.035. View

Pourrajab F, Babaei Zarch M, Baghi Yazdi M, Rahimi Zarchi A, Vakili Zarch A . Application of stem cell/growth factor system, as a multimodal therapy approach in regenerative medicine to improve cell therapy yields. Int J Cardiol. 2014; 173(1):12-9. DOI: 10.1016/j.ijcard.2014.02.006. View

Ravingerova T, Tribulova N, Slezak J, Curtis M . Brief, intermediate and prolonged ischemia in the isolated crystalloid perfused rat heart: relationship between susceptibility to arrhythmias and degree of ultrastructural injury. J Mol Cell Cardiol. 1995; 27(9):1937-51. DOI: 10.1016/0022-2828(95)90016-0. View

Curtis M, Walker M . Quantification of arrhythmias using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischaemia. Cardiovasc Res. 1988; 22(9):656-65. DOI: 10.1093/cvr/22.9.656. View

Lassaletta A, Elmadhun N, Zanetti A, Feng J, Anduaga J, Gohh R . Rapamycin treatment of healthy pigs subjected to acute myocardial ischemia-reperfusion injury attenuates cardiac functions and increases myocardial necrosis. Ann Thorac Surg. 2013; 97(3):901-7. PMC: 3943541. DOI: 10.1016/j.athoracsur.2013.09.059. View

Jia Y, Mo S, Feng Q, Zhan M, Ouyang L, Chen J . EPO-dependent activation of PI3K/Akt/FoxO3a signalling mediates neuroprotection in in vitro and in vivo models of Parkinson's disease. J Mol Neurosci. 2014; 53(1):117-24. DOI: 10.1007/s12031-013-0208-0. View

Yin X, Zheng Y, Zhai X, Zhao X, Cai L . Diabetic inhibition of preconditioning- and postconditioning-mediated myocardial protection against ischemia/reperfusion injury. Exp Diabetes Res. 2011; 2012:198048. PMC: 3148591. DOI: 10.1155/2012/198048. View

Kim H, Joe Y, Kong J, Jeong S, Cho G, Ryter S . Carbon monoxide protects against hepatic ischemia/reperfusion injury via ROS-dependent Akt signaling and inhibition of glycogen synthase kinase 3β. Oxid Med Cell Longev. 2014; 2013:306421. PMC: 3880761. DOI: 10.1155/2013/306421. View

Hofmann B, Jucker M . Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85α regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain. Cell Signal. 2012; 24(10):1950-4. DOI: 10.1016/j.cellsig.2012.06.009. View

10.

Du X, Hu X, Wei J . Anti-inflammatory effect of exendin-4 postconditioning during myocardial ischemia and reperfusion. Mol Biol Rep. 2014; 41(6):3853-7. DOI: 10.1007/s11033-014-3252-0. View

11.

Dong L, Li S, Zhen Y, Wang Y, Shao X, Luo Z . Cardioprotection of vitexin on myocardial ischemia/reperfusion injury in rat via regulating inflammatory cytokines and MAPK pathway. Am J Chin Med. 2013; 41(6):1251-66. DOI: 10.1142/S0192415X13500845. View

12.

Yan X, Qiu W, Jia B, Zhong H, Li X, Chen Z . Myocardial protection by interferon-γ late preconditioning during cardiopulmonary bypass‑associated myocardial ischemia-reperfusion in pigs. Oncol Rep. 2013; 30(5):2145-52. DOI: 10.3892/or.2013.2707. View

13.

Zhang J, Yao Y, Xiao F, Lan X, Yu C, Zhang Y . Administration of dexamethasone protects mice against ischemia/reperfusion induced renal injury by suppressing PI3K/AKT signaling. Int J Clin Exp Pathol. 2013; 6(11):2366-75. PMC: 3816805. View

14.

Wu B, Meng K, Ji Q, Cheng M, Yu K, Zhao X . Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice. Clin Exp Immunol. 2014; 176(3):438-51. PMC: 4008989. DOI: 10.1111/cei.12284. View

15.

Chen K, Li G, Geng F, Zhang Z, Li J, Yang M . Berberine reduces ischemia/reperfusion-induced myocardial apoptosis via activating AMPK and PI3K-Akt signaling in diabetic rats. Apoptosis. 2014; 19(6):946-57. DOI: 10.1007/s10495-014-0977-0. View

16.

Westin J . Status of PI3K/Akt/mTOR pathway inhibitors in lymphoma. Clin Lymphoma Myeloma Leuk. 2014; 14(5):335-42. PMC: 4125533. DOI: 10.1016/j.clml.2014.01.007. View

17.

Shrimali D, Shanmugam M, Kumar A, Zhang J, Tan B, Ahn K . Targeted abrogation of diverse signal transduction cascades by emodin for the treatment of inflammatory disorders and cancer. Cancer Lett. 2013; 341(2):139-49. DOI: 10.1016/j.canlet.2013.08.023. View

18.

Chang W, Zhang M, Li J, Meng Z, Xiao D, Wei S . Berberine attenuates ischemia-reperfusion injury via regulation of adenosine-5'-monophosphate kinase activity in both non-ischemic and ischemic areas of the rat heart. Cardiovasc Drugs Ther. 2012; 26(6):467-78. DOI: 10.1007/s10557-012-6422-0. View

19.

Cui G, Qin X, Zhang Y, Gong Z, Ge B, Zang Y . Berberine differentially modulates the activities of ERK, p38 MAPK, and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice. J Biol Chem. 2009; 284(41):28420-28429. PMC: 2788891. DOI: 10.1074/jbc.M109.012674. View

20.

Briest F, Grabowski P . PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms. Theranostics. 2014; 4(4):336-65. PMC: 3936289. DOI: 10.7150/thno.7851. View