J Appl Biomed 16:274-280, 2018 | DOI: 10.1016/j.jab.2018.02.005

Naringenin alleviates high D-glucose-induced injuries through upregulation of microRNA-30d-5p level in human AC16 cardiac cells

Jiamei Jianga, Guobiao Lianga, Zijun Wua, Hailiang Moa, Qiong Youa, Zhiqiang Wangb, Keng Wua,*, Runmin Guoa,*
a Guangdong Medical University, Affiliated Hospital, Department of Cardiology, Zhanjiang, China
b Guangdong Medical University, Affiliated Hospital, Clinical Research Center, Zhanjiang, China

As a common complication of diabetes mellitus (DM), diabetic cardiomyopathy (DCM) is considered to be one of the major causes of mortality and morbidity. The therapeutic effects of naringenin have been verified in the treatment of various human diseases. However, the application of naringenin in the treatment of DCM still has not been reported. In this study, human AC16 cardiac cells were treated with normal d-glucose and high d-glucose (HG). After transfection with miR-30d-5p inhibitor, Cell Counting Kit-8 (CCK-8) method was used to measure cell viability. Hoechst 33258 staining was performed to observe the morphological changes of nucleus. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the activity of caspase-3. Cell apoptosis was detected by Annexin V-FITC/propidium iodide (PI) staining. Levels of light chain 3 (LC3) including LC3-I and LC3-II as well as nucleoporin p62 (P62) were detected by Western blot. We found that Naringenin treatment increased the reduced cell variability caused by HG treatment. Naringenin also increased expression level of miR-30d-5p in human AC16 cardiac cells after HG treatment. Treatment with miR-30d-5p inhibitor reduced the effect of miR-30d-5p in increasing cell variability and reducing cell apoptosis. Naringenin treatment reduced the increased levels of LC-I, LC-II and P62, but miR-30d-5p inhibitor reduced those changes. Therefore we concluded that naringenin could alleviate HG-induced injuries through the upregulation of microRNA-30d-5p level in human AC16 cardiac cells.

Keywords: Diabetes mellitus; Diabetic cardiomyopathy; Naringenin; Variability; Apoptosis

Received: October 16, 2017; Revised: January 24, 2018; Accepted: February 21, 2018; Published: November 1, 2018  Show citation

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Jiang J, Liang G, Wu Z, Mo H, You Q, Wang Z, et al.. Naringenin alleviates high D-glucose-induced injuries through upregulation of microRNA-30d-5p level in human AC16 cardiac cells. J Appl Biomed. 2018;16(4):274-280. doi: 10.1016/j.jab.2018.02.005.
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References

  1. Boudina, S., Abel, E.D., 2010. Diabetic cardiomyopathy, causes and effects. Rev. Endocr. Metab. Disord. 11 (1), 31-39. Go to original source... Go to PubMed...
  2. Bugger, H., Abel, E.D., 2014. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia 57 (4), 660-671. Go to original source... Go to PubMed...
  3. Burke, A.C., Sutherland, B.G., Assini, J.M., Huff, M.W., 2015. Abstract 686: intervention with naringenin enhances weight loss, potentiates improvements in metabolic dysregulation and halts progression of atherosclerosis induced by a high-fat diet in LDLr-/-mice. Arterioscler. Thromb. Vasc. Biol. 35 (1), A686. Go to original source...
  4. Burke, A.C., Telford, D.E., Sutherland, B.G., Edwards, J.Y., Huff, M.W., 2017. Naringenin supplementation to a chow diet reduces plasma lipids and adiposity, and suppresses Rer in Ldlr-/-mice fed a chow diet. Arterioscler. Thromb. Vasc. Biol. 37 (1), A369. Go to original source...
  5. Chen, Y., Zhang, J., Wang, H., Zhao, J., Xu, C., Du, Y., et al., 2012. miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10. BMC Cancer 12, 111. Go to original source... Go to PubMed...
  6. Chen, D., Guo, W., Qiu, Z., Wang, Q., Li, Y., Liang, L., et al., 2015. MicroRNA-30d-5p inhibits tumour cell proliferation and motility by directly targeting CCNE2 in non-small cell lung cancer. Cancer Lett. 362 (2), 208-217. Go to original source... Go to PubMed...
  7. Chtourou, Y., Slima, A.B., Makni, M., Gdoura, R., Fetoui, H., 2015. Naringenin protects cardiac hypercholesterolemia-induced oxidative stress and subsequent necroptosis in rats. Pharmacol. Rep. 67 (6), 1090-1097. Go to original source... Go to PubMed...
  8. Curti, V., Di Lorenzo, A., Rossi, D., Martino, E., Capelli, E., Collina, S., et al., 2017. Enantioselective modulatory effects of naringenin enantiomers on the expression levels of miR-17-3p involved in endogenous antioxidant defenses. Nutrients 9 (3), 215. Go to original source... Go to PubMed...
  9. Huynh, K., Bernardo, B.C., McMullen, J.R., Ritchie, R.H., 2014. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol. Ther. 142 (3), 375-415. Go to original source... Go to PubMed...
  10. Jia, K., Shi, P., Han, X., Chen, T., Tang, H., Wang, J., 2016. Diagnostic value of miR-30d5p and miR-125b-5p in acute myocardial infarction. Mol. Med. Rep. 14 (1), 184- 194. Go to original source... Go to PubMed...
  11. Kapoor, R., Kakkar, P., 2014. Naringenin accords hepatoprotection from streptozotocin induced diabetes in vivo by modulating mitochondrial dysfunction and apoptotic signaling cascade. Toxicol. Rep. 1, 569-581. Go to original source... Go to PubMed...
  12. Kuida, K., Haydar, T.F., Kuan, C.Y., Gu, Y., Taya, C., Karasuyama, H., et al., 1998. Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94 (3), 325-337. Go to original source... Go to PubMed...
  13. Li, X., Du, N., Zhang, Q., Li, J., Chen, X., Liu, X., et al., 2014. MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy. Cell Death Dis. 5 (10), e1479. Go to original source... Go to PubMed...
  14. Lorenzo-Almorós, A., Tuñón, J., Orejas, M., Cortés, M., Egido, J., Lorenzo, Ó., 2017. Diagnostic approaches for diabetic cardiomyopathy. Cardiovasc. Diabetol. 16 (1), 28. Go to original source... Go to PubMed...
  15. Miki, T., Yuda, S., Kouzu, H., Miura, T., 2013. Diabetic cardiomyopathy: pathophysiology and clinical features. Heart Fail. Rev. 18 (2), 149-166. Go to original source... Go to PubMed...
  16. Reddy, K.B., 2015. MicroRNA (miRNA) in cancer. Cancer Cell Int. 15 (1), 38. Go to original source... Go to PubMed...
  17. Shenoy, A., Blelloch, R.H., 2014. Regulation of microRNA function in somatic stem cell proliferation and differentiation. Nat. Rev. Mol. Cell Biol. 15 (9), 565. Go to original source... Go to PubMed...
  18. Shi, L.B., Tang, P.F., Zhang, W., Zhao, Y.P., Zhang, L.C., Zhang, H., 2016. Naringenin inhibits spinal cord injury-induced activation of neutrophils through miR-223. Gene 592 (1), 128-133. Go to original source... Go to PubMed...
  19. Tarquini, R., Lazzeri, C., Pala, L., Rotella, C.M., Gensini, G.F., 2011. The diabetic cardiomyopathy. Acta Diabetol. 48 (3), 173-181. Go to original source... Go to PubMed...