Open Access

Berberine protects myocardial cells against anoxia‑reoxygenation injury via p38 MAPK‑mediated NF‑κB signaling pathways

  • Authors:
    • Yu Zhao
    • Xuefeng Tian
    • Gengfeng Liu
    • Kuijing Wang
    • Yuanyuan Xie
    • Yuxuan Qiu
  • View Affiliations

  • Published online on: November 9, 2018     https://doi.org/10.3892/etm.2018.6949
  • Pages: 230-236
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Ischemic heart disease is a leading cause of mortality and occurs due to coronary arterial atherosclerosis, vascular cavity stenosis and occlusion. It has previously been demonstrated that berberine treatment may ameliorate and help to prevent cardiovascular diseases due to its anti‑inflammatory and anti‑apoptotic effects in myocardial cells. However, the potential signaling mechanisms mediated by berberine in the progression of myocardial injury remain to be elucidated. The aim of the present study was to investigate the therapeutic effects of berberine and its potential mechanism in a mouse model of myocardial cell injury. The results revealed that berberine treatment downregulated the serum expression of inflammatory factors, including interleukin (IL)‑6, tumor necrosis factor‑α, IL‑10 and IL‑17A in mice with anoxia‑reoxygenation injury. Berberine treatment also decreased myocardial cell apoptosis following anoxia‑reoxygenation injury via regulating the expression of apoptosis‑associated genes. Histological analysis revealed that the area, circumference fragmentation and segmentation of myocardial cells were significantly decreased by berberine treatment compared with the control group. The body weight, blood lipid levels, blood pressure and heart rate were markedly improved in mice with anoxia‑reoxygenation injury following berberine treatment compared with untreated mice. The expression of p38 mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB expression was downregulated in myocardial cells from in mice with anoxia‑reoxygenation injury following berberine treatment compared with untreated mice. However, p38 MAPK overexpression ameliorated the berberine‑induced decrease in NF‑κB activity and expression, as well as the berberine‑induced inhibition of myocardial apoptosis in myocardial cells isolated from experimental mice. In conclusion, the results of the present study indicate that berberine is able to decrease the expression of inflammatory cytokines expression and inhibit myocardial cell apoptosis via downregulating the p38 MAPK‑mediated NF‑κB signaling pathway. These results suggest that berberine may be an effective treatment for anoxia‑reoxygenation injury.

References

1 

Sankari A, Martin JL and Badr M: A retrospective review of sleep-disordered breathing, hypertenstion and cardiovascular diseases in spinal cord injury patients. Spinal Cord. 53:496–497. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Piepoli MF, Corra U, Abreu A, Cupples M, Davos C, Doherty P, Höfer S, Garcia-Porrero E, Rauch B, Vigorito C, et al: Challenges in secondary prevention of cardiovascular diseases: A review of the current practice. Int J Cardiol. 180:114–119. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Kozlovskaya IL, Bulkina OS, Lopukhova VV, Chernova NA, Ivanova OV, Kolmakova TE and Karpov YA: Heat and cardiovascular diseases: A review of epidemiological surveys. Ter Arkh. 87:84–90. 2015.(In Russian). View Article : Google Scholar : PubMed/NCBI

4 

Klainin-Yobas P, Ng SH, Stephen PDM and Lau Y: Efficacy of psychosocial interventions on psychological outcomes among people with cardiovascular diseases: A systematic review and meta-analysis. Patient Educ Couns. 99:512–521. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Wang XQ, Pi YL, Chen PJ, Liu Y, Wang R, Li X, Chen BL, Zhu Y, Yang YJ and Niu ZB: Traditional Chinese exercise for cardiovascular diseases: Systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 5:e0025622016. View Article : Google Scholar : PubMed/NCBI

6 

Zulli A, Smith RM, Kubatka P, Novak J, Uehara Y, Loftus H, Qaradakhi T, Pohanka M, Kobyliak N, Zagatina A, et al: Caffeine and cardiovascular diseases: Critical review of current research. Eur J Nutr. 55:1331–1343. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Baselet B, Rombouts C, Benotmane AM, Baatout S and Aerts A: Cardiovascular diseases related to ionizing radiation: The risk of low-dose exposure (Review). Int J Mol Med. 38:1623–1641. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Fatema K, Zwar NA, Milton AH, Ali L and Rahman B: Prevalence of risk factors for cardiovascular diseases in bangladesh: A systematic review and meta-analysis. PLoS One. 11:e01601802016. View Article : Google Scholar : PubMed/NCBI

9 

Wang L, Xue Y, Ma H, Shi H, Wang L and Cui X: Prazosin protects myocardial cells against anoxia-reoxygenation injury via the extracellular signalregulated kinase signaling pathway. Mol Med Rep. 17:2145–2152. 2018.PubMed/NCBI

10 

Aminde LN and Veerman L: Interventions for the prevention of cardiovascular diseases: A protocol for a systematic review of economic evaluations in low-income and middle-income countries. BMJ Open. 6:e0136682016. View Article : Google Scholar : PubMed/NCBI

11 

De Lorgeril M: Essential polyunsaturated fatty acids, inflammation, atherosclerosis and cardiovascular diseases. Subcell Biochem. 42:283–297. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Candore G, Aquino A, Balistreri CR, Bulati M, Di Carlo D, Grimaldi MP, Listì F, Orlando V, Vasto S, Caruso M, et al: Inflammation, longevity, and cardiovascular diseases: Role of polymorphisms of TLR4. Ann N Y Acad Sci. 1067:282–287. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Jiang Q, Liu P, Wu X, Liu W, Shen X, Lan T, Xu S, Peng J, Xie X and Huang H: Berberine attenuates lipopolysaccharide-induced extracelluar matrix accumulation and inflammation in rat mesangial cells: Involvement of NF-κB signaling pathway. Mol Cell Endocrinol. 331:34–40. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Chang W, Zhang M, Li J, Meng Z, Xiao D, Wei S, Chen L, Wang C and Hatch GM: 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. 26:467–478. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Zhao GL, Yu LM, Gao WL, Duan WX, Jiang B, Liu XD, Zhang B, Liu ZH, Zhai ME, Jin ZX, et al: Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress. Acta Pharmacol Sin. 37:354–367. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Davey G and Wu Z: Attitudes in China toward the use of animals in laboratory research. Altern Lab Anim. 35:313–316. 2007.PubMed/NCBI

17 

Jong WM, Ten Cate H, Linnenbank AC, de Boer OJ, Reitsma PH, de Winter RJ and Zuurbier CJ: Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model. Inflamm Res. 65:489–499. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Barile L, Chimenti I, Gaetani R, Forte E, Miraldi F, Frati G, Messina E and Giacomello A: Cardiac stem cells: Isolation, expansion and experimental use for myocardial regeneration. Nat Clin Pract Cardiovasc Med. 4 Suppl 1:S9–S14. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Jin Y and Blikslager AT: Myosin light chain kinase mediates intestinal barrier dysfunction via occludin endocytosis during anoxia/reoxygenation injury. Am J Physiol Cell Physiol. 311:C996–C1004. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Huang H, Lai S, Wan Q, Qi W and Liu J: Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein. Can J Physiol Pharmacol. 94:542–553. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Xia WF, Liu Y, Zhou QS, Tang QZ and Zou HD: Comparison of the effects of propofol and midazolam on inflammation and oxidase stress in children with congenital heart disease undergoing cardiac surgery. Yonsei Med J. 52:326–332. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Zhang R, Zhang YY, Huang XR, Wu Y, Chung AC, Wu EX, Szalai AJ, Wong BC, Lau CP and Lan HY: C-reactive protein promotes cardiac fibrosis and inflammation in angiotensin II-induced hypertensive cardiac disease. Hypertension. 55:953–960. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Dong SF, Hong Y, Liu M, Hao YZ, Yu HS, Liu Y and Sun JN: Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats. Eur J Pharmacol. 660:368–374. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Zhang YJ, Yang SH, Li MH, Iqbal J, Bourantas CV, Mi QY, Yu YH, Li JJ, Zhao SL, Tian NL and Chen SL: Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: Role of autophagy. Clin Exp Pharmacol Physiol. 41:995–1002. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Huang Z, Han Z, Ye B, Dai Z, Shan P, Lu Z, Dai K, Wang C and Huang W: Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes. Eur J Pharmacol. 762:1–10. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Wang YY, Li HM, Wang HD, Peng XM, Wang YP, Lu DX, Qi RB, Hu CF and Jiang JW: Pretreatment with berberine and yohimbine protects against LPS-induced myocardial dysfunction via inhibition of cardiac I-[kappa]B[alpha] phosphorylation and apoptosis in mice. Shock. 35:322–328. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Zhang XD, Ren HM and Liu L: Effects of different dose berberine on hemodynamic parameters and [Ca2+]i of cardiac myocytes of diastolic heart failure rat model. Zhongguo Zhong Yao Za Zhi. 33:818–821. 2008.(In Chinese). PubMed/NCBI

29 

Chen H, Zhang RQ, Wei XG, Ren XM and Gao XQ: Mechanism of TLR-4/NF-κB pathway in myocardial ischemia reperfusion injury of mouse. Asian Pac J Trop Med. 9:503–507. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

January 2019
Volume 17 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Zhao, Y., Tian, X., Liu, G., Wang, K., Xie, Y., & Qiu, Y. (2019). Berberine protects myocardial cells against anoxia‑reoxygenation injury via p38 MAPK‑mediated NF‑κB signaling pathways. Experimental and Therapeutic Medicine, 17, 230-236. https://doi.org/10.3892/etm.2018.6949
MLA
Zhao, Y., Tian, X., Liu, G., Wang, K., Xie, Y., Qiu, Y."Berberine protects myocardial cells against anoxia‑reoxygenation injury via p38 MAPK‑mediated NF‑κB signaling pathways". Experimental and Therapeutic Medicine 17.1 (2019): 230-236.
Chicago
Zhao, Y., Tian, X., Liu, G., Wang, K., Xie, Y., Qiu, Y."Berberine protects myocardial cells against anoxia‑reoxygenation injury via p38 MAPK‑mediated NF‑κB signaling pathways". Experimental and Therapeutic Medicine 17, no. 1 (2019): 230-236. https://doi.org/10.3892/etm.2018.6949