Berberine Alleviates Myocardial Ischemia-reperfusion Injury by Inhibiting Inflammatory Response and Oxidative Stress: the Key Function of MiR-26b-5p-mediated PTGS2/MAPK Signal Transduction

Overview

Journal Pharm Biol

Specialties Pharmacology
Pharmacy

Date 2022 Mar 21

PMID 35311466

Authors

Xiaojing Jia

Wei Shao

Suqing Tian

Affiliations

Soon will be listed here.

Abstract

Context: Berberine has myocardial protective effects.

Objectives: The protective effects of berberine on heart ischemia-reperfusion (I/R) injury were explored.

Materials And Methods: Human cardiomyocytes were divided into control group, oxygen-glucose deprivation/re-oxygen (OGD/R) (2 h OGD with 24 h reoxygenation) group, OGD/R + low group (5 μM berberine for 24 h) and OGD/R + high group (10 μM berberine for 24 h). Twenty-four Wistar rats were divided into sham group, I/R group (45 min occlusion with 2 h reperfusion), I/R + berberine group (50 mg/kg berberine 1 h before I/R surgery) and I/R + berberine + antagomir (intraperitoneally injected with miR-26b-5p antagomir). MicroRNA profile, effects of berberine on I/R or OGD/R-induced injuries, and the role of miR-26b-5p in the function of berberine were explored.

Results: OGD/R treatment suppressed viability (0.41 ± 0.05 vs. 0.87 ± 0.13, < 0.05), while induced apoptosis (6.6 ± 1.0% vs. 26.3 ± 4.8%, < 0.05) in cardiomyocytes, which was restored by berberine (viability: 0.64 ± 0.01 for 5 μM and 0.72 ± 0.01 for 10 μM, < 0.05; apoptosis: 10.9 ± 2.2 for 5 μM and 7.9 ± 1.3 for 10 μM). Berberine induced miR-26b-5p and inhibited PTGS2/MAPK pathway. MiR-26b-5p inhibition counteracted the protective function of berberine. In rats, berberine (50 mg/kg) improved heart histological structure and suppressed inflammatory response, which was impaired by miR-26b-5p inhibition.

Discussion And Conclusions: Berberine exerted anti-I/R function in heart by inducing miR-26b-5p and suppressing the PTGS2/MAPK pathway. These data promote the application of berberine as an anti-I/R agent.

Citing Articles

Natural products for the treatment of ulcerative colitis: focus on the JAK/STAT pathway.

Long D, Mao C, Zhang W, Zhu Y, Xu Y Front Immunol. 2025; 16:1538302.

PMID: 40078988 PMC: 11897526. DOI: 10.3389/fimmu.2025.1538302.

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

Yang H, Cao G, Li X, Zhao Z, Wang Y, Xu F Biologics. 2025; 19:31-42.

PMID: 40026702 PMC: 11871928. DOI: 10.2147/BTT.S479430.

miRNA-541-5p regulates myocardial ischemia-reperfusion injury by targeting ferroptosis.

Zhao Z, Li B, Cheng D, Leng Y J Cardiothorac Surg. 2025; 20(1):63.

PMID: 39815273 PMC: 11734549. DOI: 10.1186/s13019-024-03260-2.

METTL3, m6A modification, and EGR1: interplay affecting myocardial I/R injury outcomes.

Huang C, Zhang X, Wu S, Chang Q, Zheng Z, Xu J Cell Biol Toxicol. 2024; 41(1):7.

PMID: 39707117 PMC: 11662061. DOI: 10.1007/s10565-024-09937-7.

Based on Spectrum-Effect Relationship, Network Pharmacology, and Molecular Docking, the Material Basis and Mechanism of Antioxidant Effect of Miao Medicine Lindl Were Studied.

Liu G, Zhou L, Mu K, Peng L, Ran F, Feng G ACS Omega. 2024; 9(41):42199-42211.

PMID: 39431090 PMC: 11483384. DOI: 10.1021/acsomega.4c04212.

References

Chung J, Choi R, Seo E, Nam J, Dong M, Shin E . Anti-inflammatory effects of (Z)-ligustilide through suppression of mitogen-activated protein kinases and nuclear factor-κB activation pathways. Arch Pharm Res. 2012; 35(4):723-32. DOI: 10.1007/s12272-012-0417-z. View

Bang C, Batkai S, Dangwal S, Gupta S, Foinquinos A, Holzmann A . Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest. 2014; 124(5):2136-46. PMC: 4001534. DOI: 10.1172/JCI70577. View

Al-Salam S, Hashmi S . Myocardial Ischemia Reperfusion Injury: Apoptotic, Inflammatory and Oxidative Stress Role of Galectin-3. Cell Physiol Biochem. 2018; 50(3):1123-1139. DOI: 10.1159/000494539. View

Smeets P, Teunissen B, Planavila A, de Vogel-van den Bosch H, Willemsen P, van der Vusse G . Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by peroxisome proliferator-activated receptors PPARalpha and PPARdelta. J Biol Chem. 2008; 283(43):29109-18. PMC: 2662011. DOI: 10.1074/jbc.M802143200. View

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

Zampetaki A, Mayr M . MicroRNAs in vascular and metabolic disease. Circ Res. 2012; 110(3):508-22. DOI: 10.1161/CIRCRESAHA.111.247445. View

Huang Z, Han Z, Ye B, Dai Z, Shan P, Lu Z . Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes. Eur J Pharmacol. 2015; 762:1-10. DOI: 10.1016/j.ejphar.2015.05.028. View

Shangguan Y, Han J, Su H . GAS5 knockdown ameliorates apoptosis and inflammatory response by modulating miR-26b-5p/Smad1 axis in cerebral ischaemia/reperfusion injury. Behav Brain Res. 2019; 379:112370. DOI: 10.1016/j.bbr.2019.112370. View

Himaya S, Ryu B, Qian Z, Kim S . Paeonol from Hippocampus kuda Bleeler suppressed the neuro-inflammatory responses in vitro via NF-κB and MAPK signaling pathways. Toxicol In Vitro. 2012; 26(6):878-87. DOI: 10.1016/j.tiv.2012.04.022. View

10.

Peters L, Biessen E, Hohl M, Weber C, van der Vorst E, Santovito D . Small Things Matter: Relevance of MicroRNAs in Cardiovascular Disease. Front Physiol. 2020; 11:793. PMC: 7358539. DOI: 10.3389/fphys.2020.00793. View

11.

Yellon D, Hausenloy D . Myocardial reperfusion injury. N Engl J Med. 2007; 357(11):1121-35. DOI: 10.1056/NEJMra071667. View

12.

Piper H, Garcia-Dorado D, Ovize M . A fresh look at reperfusion injury. Cardiovasc Res. 1998; 38(2):291-300. DOI: 10.1016/s0008-6363(98)00033-9. View

13.

Rorabaugh B, Mabe N, Seeley S, Stoops T, Mucher K, Ney C . Myocardial fibrosis, inflammation, and altered cardiac gene expression profiles in rats exposed to a predator-based model of posttraumatic stress disorder. Stress. 2019; 23(2):125-135. PMC: 6982550. DOI: 10.1080/10253890.2019.1641081. View

14.

Keeley E, Boura J, Grines C . Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003; 361(9351):13-20. DOI: 10.1016/S0140-6736(03)12113-7. View

15.

Yu Z, Wang S, Zhang X, Li Y, Zhao Q, Liu T . Pterostilbene protects against myocardial ischemia/reperfusion injury via suppressing oxidative/nitrative stress and inflammatory response. Int Immunopharmacol. 2016; 43:7-15. DOI: 10.1016/j.intimp.2016.11.018. View

16.

Peuhkurinen K . [Myocardial reperfusion--a double-edged sword?]. Duodecim. 1989; 105(9):822-30. View

17.

Ge Z, Zhu X, Wang B, Hu J, Sun J, Wang S . MicroRNA-26b relieves inflammatory response and myocardial remodeling of mice with myocardial infarction by suppression of MAPK pathway through binding to PTGS2. Int J Cardiol. 2019; 280:152-159. DOI: 10.1016/j.ijcard.2018.12.077. View

18.

Thum T . MicroRNA therapeutics in cardiovascular medicine. EMBO Mol Med. 2011; 4(1):3-14. PMC: 3376835. DOI: 10.1002/emmm.201100191. View

19.

Zeng X, Zeng X, Li Y . Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2003; 92(2):173-6. DOI: 10.1016/s0002-9149(03)00533-2. View

20.

Ren J, Avery J, Zhao H, Schneider J, Ross F, Muslin A . Beta3 integrin deficiency promotes cardiac hypertrophy and inflammation. J Mol Cell Cardiol. 2006; 42(2):367-77. DOI: 10.1016/j.yjmcc.2006.11.002. View