Protective effects of berberine on intestinal ischemia and reperfusion injury in rats
Keywords:protective effects, berberine, intestinal, ischemia reperfusion injury, rats
This study aims to investigate the potential protective effects of berberine on ischemia and reperfusion (IR) injury in rats. Thirty male rats were randomly divided into three experimental groups as follows: the sham group, the IR group and the berberine+IR group. Intestinal ischemia-reperfusion was performed by occlusion of the superior mesenteric artery for 30 min, followed by 2-h reperfusion. The berberine+IR group of rats were administered 200 mg/kg of berberine once a day for 7 days before laparotomy. Compared with the IR group, rats pretreated with berberine prior to IR had significantly reduced intestinal ischemia/reperfusion injury and a significant reduction in Chiu’s score (p<0.05). The level of malondialdehyde and myeloperoxidase in the berberine+IR group was significantly decreased compared with the IR group (p<0.001). Superoxide dismutase activity in the berberine+IR group was significantly higher than in the IR group (p<0.001). Compared with the IR group, diamine oxidase was markedly decreased in the berberine+IR group (p<0.01). The level of secretory immunoglobulin A in the berberine+IR group was significantly increased when compared to the IR group (p<0.001). Our results suggest that berberine can protect from intestinal IR injury and that it can be beneficial in treating conditions associated with intestinal IR injury.
Received: January 14, 2016; Revised: February 28, 2016; Accepted: February 28, 2016; Published online: July 28, 2016
How to cite this article: Chen T, Lv B. Protective effects of berberine on intestinal ischemia and reperfusion injury in rats. Arch Biol Sci. 2017;69(1):45-51.
Nankervis CA, Giannone PJ, Reber KM. The neonatal intestinal vasculature: contributing factors to necrotizing enterocolitis. Semin Perinatol. 2008;32(2):83-91.
Olivier C, Alexandre N. Gastro-intestinal vascular emergencies. Best Pract Res Clin Gastroenterol. 2013;27(5):709-25.
Fishman JE, Sheth SU, Levy G，Alli V, Lu Q, Xu D, Qin Y, Qin X, Deitch EA. Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock. Ann Surg. 2014;260(6):1112-20.
Röth E, Hejjel L, Jaberansari M, Jancso G. The role of free radicals in endogenous adaptation and intracellular signals. Exp Clin Cardiol. 2004;9(1):13-6.
Riaz AA, Wan MX, Schäfer T, Dawson P, Menger MD, Jeppsson B, Thorlacius H. Allopurinol and superoxide dismutase protect against leucocyte-endothelium interactions in a novel model of colonic ischaemia-reperfusion. Br J Surg. 2002;89(12):1572-80.
Amani Nabil S. Febuxostat Improves the Local and Remote Organ Changes Induced by Intestinal Ischemia/Reperfusion in Rats. Digest Dis Sci. 2012;58(3):650-9.
Lenka G, Jirí D, Radek M. Quaternary protoberberine alkaloids. J Cheminform. 2007;38(19):150-75.
Komal S, Ranjan B, Neelam C, Birendra S. Berberis aristata: A Review. Int J Res Ayurveda and Pharmacy, 2011;2(2):383-8.
Kumar A, Ekavali, Chopra K, Mukherjee M, Pottabathini R, Dhull DK. Current knowledge and pharmacological profile of berberine: An update. Eur J Pharmacol. 2015;761:288-97.
Battu SK, Repka MA, Maddineni S, Chittiboyina AG, Avery MA, Majumdar S. Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery. AAPS PharmSciTech. 2010;11(3):1466-75.
Abd El-Wahab AE, Ghareeb DA, Sarhan EE, Abu-Serie MM, El Demellawy MA. In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. Bmc Complem Altern M. 2013;13(1):218-23.
Balestrini L, Isolani ME, Pietra D, Borghini A, Bianucci AM, Deri P, Batistoni R. Berberine exposure triggers developmental effects on planarian regeneration. Sci Rep. 2014;4(6184):649-52.
Wang L, Liu L, Shi Y, Cao H, Chaturvedi R, Calcutt MW, Hu T, Ren X, Wilson KT, Polk DB, Yan F. Berberine induces caspase-independent cell death in colon tumor cells through activation of apoptosis-inducing factor. Plos One. 2012;7(5):e36418.
Zhang J, Cao H, Zhang B, Cao H, Xu X, Ruan H, Yi T, Tan L, Qu R, Song G, Wang B, Hu T. Berberine potently attenuates intestinal polyps’ growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling. J Cell Mol Med. 2013;17(11):1484-93.
Wang L, Cao H, Lu N, Liu L, Wang B, Hu T, Israel DA, Peek RM Jr, Polk DB, Yan F. Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells. Plos One. 2013;8(2):e56666.
Wang J, Peng Y, Liu Y, Yang J, Ding N, Tan W. Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and cancer growth. Bmc Cancer. 2015;15(1):1-9.
Negar P, Massoud M, Pejman M, Goudarz Sadeghi H. Effects of berberine on β-secretase activity in a rabbit model of Alzheimer’s disease. Arch Med Sci. 2013;9(1):146-50.
Yu L, Li F, Zhao G, Yang Y, Jin Z, Zhai M, Yu W, Zhao L, Chen W, Duan W, Yu S. Protective effect of berberine against myocardial ischemia reperfusion injury: Role of Notch1/Hes1-PTEN/Akt signaling. Apoptosis. 2015;20(6):796-810.
Zhang X, Zhao Y, Zhang M, Pang X, Xu J, Kang C, Li M, Zhang C, Zhang Z, Zhang Y, Li X, Ning G, Zhao L. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. Plos One. 2012;7(8): e42529.
Sun SF, Zhao TT, Zhang HJ, Huang XR, Zhang WK, Zhang L, Yan MH, Dong X, Wang H, Wen YM, Pan XP, Lan HY, Li P. Renoprotective effect of berberine on type 2 diabetic nephropathy in rats. Clin Exp Pharmacol P. 2015;42(6):662–70.
Dong H, Wang N, Zhao L, Lu F. Berberine in the Treatment of Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis. Evid-Based Compl Alt. 2012;2012(6):591654.
Chiu CJ, Mcardle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg. 1970;101(4):478-83.
Blikslager AT. Treatment of gastrointestinal ischemic injury. Vet Clin North Am Equine Pract. 2003;19(3):715-27.
Gregory KE, Deforge CE, Natale KM, Michele P, Marter LJ, Van. Necrotizing enterocolitis in the premature infant: neonatal nursing assessment, disease pathogenesis, and clinical presentation. Adv Neonatal Care. 2011;11(3):e783-e789.
Trompeter M, Brazda T, Remy CT, Vestring T, Reimer P. Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy. Eur Radiol. 2002;12(5):1179-87.
Yasuhara H. Acute mesenteric ischemia: the challenge of gastroenterology. Surg Today. 2005;35(3):185-95.
Akcılar R, Akcılar A, Koçak C, Koçak FE, Bayat Z, Şimşek H, Şahin S, Savran B. Effects of ukrain in rats with intestinal ischemia and reperfusion. J Surg Res. 2015;195(1):67-73.
Gu L, Li N, Yu W, Gong J, Li Q, Zhu W, Li J. Berberine reduces rat intestinal tight junction injury induced by ischemia-reperfusion associated with the suppression of inducible nitric oxide synthesis. Am J Chin Med. 2013;41(6):1297-312.
Han J, Lin H, Huang W. Modulating gut microbiota as an anti-diabetic mechanism of berberine. Med Sci Monit. 2011;17(7):RA164-RA167.
Bhutada P, Mundhada Y, Bansod K, Tawari S, Patil S, Dixit P, Umathe S, Mundhada D. Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes. Behav Brain Res. 2011;220(1):30-41.
Habtemariam S. The therapeutic potential of Berberis darwinii stem-bark: quantification of berberine and in vitro evidence for Alzheimer’s disease therapy. Nat Prod Commun. 2011;6(8):1089-90.
Wang Y, Liu J, Ma A, Chen Y. Cardioprotective effect of berberine against myocardial ischemia/reperfusion injury via attenuating mitochondrial dysfunction and apoptosis. Int J Clin Exp Med. 2015;8(8):14513-9.
Lan T, Shen X, Liu P, Liu W, Xu S, Xie X, Jiang Q, Li W, Huang H. Berberine ameliorates renal injury in diabetic C57BL/6 mice: Involvement of suppression of SphK-S1P signaling pathway. Arch Biochem Biophys. 2010;502(2):112-20.
Hai L, Bin D, Sahng Wook P, Hyun-Sook L, Wei C, Jingwen L. Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J Biol Chem. 2009;284(42):28885-95.
Kim WS, Lee YS, Cha SH, Jeong HW, Choe SS, Lee MR, Oh GT, Park HS, Lee KU, Lane MD, Kim JB. Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity. Am J Physiol-Endoc M. 2009;296(4):E812-E819.
Jing Y, Kong WJ, Jiang JD. Learning from berberine: Treating chronic diseases through multiple targets. Sci China Life Sci. 2013;57(09):1-6.
Irani K. Oxidant signaling in vascular cell growth, death, and survival: a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res. 2000;87(3):179-83.
Yildiz Y, Serter M, Ek RO, Ergin K, Cecen S, Demir EM, Yenisey C. Protective effects of caffeic acid phenethyl ester on intestinal ischemia-reperfusion injury. Digest Dis Sci. 2009;54(4):738-44.
Zhang Z, Pan C, Wang HZ, Li YX. Protective effects of osthole on intestinal ischemia-reperfusion injury in mice. Experimental & Clinical Transplantation Official Journal of the Middle East Society for Organ Transplantation. 2014;12(3):246-52.
Changmao C, Wei L, Juntian C, Xinxin L, Shenglin C. Diamine oxidase as a marker for diagnosis of superior mesenteric arterial occlusion. Hepato-gastroenterol. 2012;59(59):155-8.
Cakmaz R, Büyükaşık O, Kahramansoy N, Erkol H, Cöl C, Boran C, Buğdaycı G. A combination of plasma DAO and citrulline levels as a potential marker for acute mesenteric ischemia. Libyan J Med. 2013;8(5):1-6.
Liu L, Tan Q, Hu B, Wu H, Wang C, Liu R, Tang C. Somatostatin Improved B Cells Mature in Macaques during Intestinal Ischemia-Reperfusion. Plos One. 2015;10(7):e0133692.
How to Cite
Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.