Alpha-mangostin decreases high glucose-induced damage on human umbilical vein endothelial cells by increasing autophagic protein expression

Document Type : Original Article

Authors

1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

3 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Diabetes is a chronic disorder that occurs as a result of impaired glucose metabolism. In hyperglycaemic states, the balance between oxidative stress and antioxidant enzymes is disrupted leading to oxidative damage and cell death. In addition,  impaired autophagy leads to the storage of dysfunctional proteins and cellular organelles in the cell. Hence, the cytoprotective function of autophagy may be disrupted by high glucose conditions. Alpha-mangostin (A-MG) is an essential xanthone purified from the mangosteen fruit. The different pharmacological benefits of alpha-mangostin, including antioxidant, anti-obesity, and antidiabetic, were demonstrated. 
Materials and Methods: We evaluated the protective influence of A-MG on autophagic response impaired by high concentrations of glucose in human umbilical vein endothelial cells (HUVECs). The HUVECs were treated with various glucose concentrations (5-60 mM) and A-MG (1.25-10 μM) for three days. Then, HUVECs were treated with 60 mM of glucose+2.5 μM of A-MG to measure viability, ROS, and NO content. Finally, the levels of autophagic proteins including LC3, SIRT1, and beclin 1 were evaluated by western blot.
Results: The results expressed that high glucose condition (60 mM) decreased viability and increased ROS and NO content in HUVECs. In addition, LC3, SIRT1, and beclin 1 protein levels declined when HUVECs were exposed to the high concentration of glucose. A-MG reversed these detrimental effects and elevated autophagic protein levels.
Conclusion: Our data represent that A-MG protects HUVECs against high glucose conditions by decreasing ROS and NO generation as well as increasing the expression of autophagy proteins.

Keywords

Main Subjects

References

1. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine 2010; 38:602-606.
2. American Diabetes Association. Screening for Diabetes. Diabetes Care 2002; 25:s21-s24.
3. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27:1047-1053.
4. Ma T, Zhu J, Chen X, Zha D, Singhal PC, Ding G. High glucose induces autophagy in podocytes. Exp Cell Res 2013; 319:779-789.
5. Baehrecke EH. Autophagy: Dual roles in life and death? Nat Rev Mol Cell Biol 2005; 6:505-510.
6. Glick D, Barth S, Macleod KF. Autophagy: Cellular and molecular mechanisms. J Pathol 2010; 221:3-12.
7. Yao J, Tao ZF, Li CP, Li XM, Cao GF, Jiang Q, et al. Regulation of autophagy by high glucose in human retinal pigment epithelium. Cell Physiol Biochem 2014; 33:107-116.
8. Xie Z, Klionsky DJ. Autophagosome formation: Core machinery and adaptations. Nat Cell Biol 2007; 9:1102-1109.
9. Wang J. Beclin 1 bridges autophagy, apoptosis and differentiation. Autophagy 2008; 4:947-948.
10. Huang R, Liu W. Identifying an essential role of nuclear LC3 for autophagy. Autophagy 2015; 11:852-853.
11. Kitada M, Ogura Y, Koya D. The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. Aging (Albany N Y) 2016; 8:2290-2307.
12. Tousian H, Razavi BM, Hosseinzadeh H. Effects of alpha-mangostin on memory senescence induced by high glucose in human umbilical vein endothelial cells. Iran J Basic Med Sci 2020; 23:1261-1267.
13. Gonzalez CD, Lee MS, Marchetti P, Pietropaolo M, Towns R, Vaccaro MI, et al. The emerging role of autophagy in the pathophysiology of diabetes mellitus. Autophagy 2011; 7:2-11.
14. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 2008; 27:433-446.
15. Heidari S, Mehri S, Shariaty V, Hosseinzadeh H. Preventive effects of crocin on neuronal damages induced by D-galactose through AGEs and oxidative stress in human neuroblastoma cells (SH-SY5Y). J Pharmacopuncture 2018; 21:18-25.
16. Shahroudi MJ, Mehri S, Hosseinzadeh H. Anti-aging effect of Nigella sativa fixed oil on d-galactose-induced aging in mice. J Pharmacopuncture 2017; 20:29-35.
17. Rezabakhsh A, Rahbarghazi R, Malekinejad H, Fathi F, Montaseri A, Garjani A. Quercetin alleviates high glucose-induced damage on human umbilical vein endothelial cells by promoting autophagy. Phytomedicine 2019; 56:183-193.
18. Xu K, Liu XF, Ke ZQ, Yao Q, Guo S, Liu C. Resveratrol modulates apoptosis and autophagy induced by high glucose and palmitate in cardiac cells. Cell Physiol Biochem 2018; 46:2031-2040.
19. Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD. Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem 2006; 54:2077-2082.
20. Ibrahim MY, Hashim NM, Mariod AA, Mohan S, Abdulla MA, Abdelwahab SI, et al. α-Mangostin from Garcinia mangostana Linn: An updated review of its pharmacological properties. Arab J Chem 2016; 9:317-329.
21. Tousian H, Razavi BM, Hosseinzadeh H. Alpha-mangostin decreased cellular senescence in human umbilical vein endothelial cells. Daru 2020; 28:45-55.
22. Tousian Shandiz H, Razavi BM, Hosseinzadeh H. Review of Garcinia mangostana and its xanthones in metabolic syndrome and related complications. Phytother Res 2017; 31:1173-1182.
23. Fang Y, Su T, Qiu X, Mao P, Xu Y, Hu Z, et al. Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death. Sci Rep 2016; 6:21018.
24. Eisvand F, Imenshahidi M, Ghasemzadeh Rahbardar M, Tabatabaei Yazdi SA, Rameshrad M, Razavi BM, et al. Cardioprotective effects of alpha-mangostin on doxorubicin-induced cardiotoxicity in rats. Phytother Res 2022; 36:506-524.
25. Luo Y, Lei M. alpha-Mangostin protects against high-glucose induced apoptosis of human umbilical vein endothelial cells. Biosci Rep 2017; 37:BSR20170779.
26. Jittiporn K, Moongkarndi P, Samer J, Suvitayavat W. Protective effect of α-mangostin on high glucose induced endothelial cell apoptosis. Walailak J Sci Technol 2017; 15:579-587.
27. Rezabakhsh A, Fathi F, Bagheri HS, Malekinejad H, Montaseri A, Rahbarghazi R, et al. Silibinin protects human endothelial cells from high glucose-induced injury by enhancing autophagic response. J Cell Biochem 2018; 119:8084-8094.
28. Mousavi SH, Tavakkol-Afshari J, Brook A, Jafari-Anarkooli I. Role of caspases and Bax protein in saffron-induced apoptosis in MCF-7 cells. Food Chem Toxicol 2009; 47:1909-1913.
29. Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 1999; 27:612-616.
30. Zhang Y, Wang SJ, Han ZH, Li YQ, Xue JH, Gao DF, et al. PI3K/AKT signaling pathway plays a role in enhancement of eNOS activity by recombinant human angiotensin converting enzyme 2 in human umbilical vein endothelial cells. Int J Clin Exp Pathol 2014; 7:8112-8117.
31. Malekinejad H, Rezabakhsh A, Rahmani F, Razi M. Paraquat exposure up-regulates cyclooxygenase-2 in the lungs, liver and kidneys in rats. Iran J Pharm Res 2013; 12:887-896.
32. Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, Green-Thompson ZW, et al. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 2010; 90:1383-1435.
33. Kim KA, Shin YJ, Akram M, Kim ES, Choi KW, Suh H, et al. High glucose condition induces autophagy in endothelial progenitor cells contributing to angiogenic impairment. Biol Pharm Bull 2014; 37:1248-1252.
34. Janhom P, Dharmasaroja P. Neuroprotective effects of alpha-mangostin on MPP(+)-induced apoptotic cell death in neuroblastoma SH-SY5Y cells. J Toxicol 2015; 2015:919058.
35. Li Q, Yin Y, Zheng Y, Chen F, Jin P. Inhibition of autophagy promoted high glucose/ROS-mediated apoptosis in ADSCs. Stem Cell Res Ther 2018; 9:289.
36. Zhang C, Yu G, Shen Y. The naturally occurring xanthone alpha-mangostin induces ROS-mediated cytotoxicity in non-small scale lung cancer cells. Saudi J Biol Sci 2018; 25:1090-1095.
37. Xu Y, Zhou H, Cai L. Alpha-mangostin attenuates oxidative stress and inflammation in adjuvant-induced arthritic rats. Trop J Pharm Res 2018; 16:2611-2616.
38. Tamil Selvi A, Joseph GS, Jayaprakasha GK. Inhibition of growth and aflatoxin production in Aspergillus flavus by Garcinia indica extract and its antioxidant activity. Food Microbiol 2003; 20:455-460.
39. Balestrieri ML, Rienzo M, Felice F, Rossiello R, Grimaldi V, Milone L, et al. High glucose downregulates endothelial progenitor cell number via SIRT1. Biochim Biophys Acta 2008; 1784:936-945.
40. Yamahara K, Yasuda M, Kume S, Koya D, Maegawa H, Uzu T. The role of autophagy in the pathogenesis of diabetic nephropathy. J Diabetes Res 2013; 2013:193757.
41. Qu L, Liang X, Gu B, Liu W. Quercetin alleviates high glucose-induced Schwann cell damage by autophagy. Neural Regen Res 2014; 9:1195-1203.
42. Maejima Y, Isobe M, Sadoshima J. Regulation of autophagy by Beclin 1 in the heart. J Mol Cell Cardiol 2016; 95:19-25.
43. Gao H, Hou F, Dong R, Wang Z, Zhao C, Tang W, et al. Rho-Kinase inhibitor fasudil suppresses high glucose-induced H9c2 cell apoptosis through activation of autophagy. Cardiovasc Ther 2016; 34:352-359.
44. Xin W, Li Z, Xu Y, Yu Y, Zhou Q, Chen L, et al. Autophagy protects human podocytes from high glucose-induced injury by preventing insulin resistance. Metabolism 2016; 65:1307-1315.
45. Wang Y, Zhao X, Shi D, Chen P, Yu Y, Yang L, et al. Overexpression of SIRT1 promotes high glucose-attenuated corneal epithelial wound healing via p53 regulation of the IGFBP3/IGF-1R/AKT pathway. Invest Ophthalmol Vis Sci 2013; 54:3806-3814.
46. Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci U S A 2008; 105:3374-3379.
47. Salminen A, Kaarniranta K. SIRT1: regulation of longevity via autophagy. Cell Signal 2009; 21:1356-1360.
48. Potente M, Urbich C, Sasaki K, Hofmann WK, Heeschen C, Aicher A, et al. Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization. J Clin Invest 2005; 115:2382-2392.
49. Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 2005; 45:1449-1457.
50. Loomans CJ, de Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, de Boer HC, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes 2004; 53:195-199.
51. Zhang HH, Ma XJ, Wu LN, Zhao YY, Zhang PY, Zhang YH, et al. SIRT1 attenuates high glucose-induced insulin resistance via reducing mitochondrial dysfunction in skeletal muscle cells. Exp Biol Med (Maywood) 2015; 240:557-565.
Iranian Journal of Basic Medical Sciences
Volume 27, Issue 1
January 2024
Pages 90-96

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