A Molecular Approach on the Protective Effects of Mangiferin Against Diabetes and Diabetes-related Complications

Author(s): Sonali Aswal, Ankit Kumar, Ashutosh Chauhan, Ruchi Badoni Semwal, Abhimanyu Kumar, Deepak Kumar Semwal*

Journal Name: Current Diabetes Reviews

Volume 16 , Issue 7 , 2020


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Abstract:

Background: Diabetes and its related complications are now a global health problem without an effective therapeutic approach. There are many herbal medicines which have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets.

Aim: The aim of this study is to review available knowledge of mangiferin focusing on its mode of action.

Methods: Mangiferin was extensively reviewed for its antidiabetic activity using online database like Scopus, PubMed, and Google Scholar as well as some offline textbooks. A critical discussion based on the mechanism of action and the future perspectives is also given in the present manuscript.

Results: Mangiferin is a natural C-glucoside and mainly obtained from its primary source, the leaves of mango tree (Mangifera indica L.). Therapeutic and preventive properties of mangiferin include antimicrobial, anti-inflammatory, antioxidative, antiallergic, neuroprotective, and cognition-enhancing effects. It dissolves well in water, so it can be easily extracted into infusions and decoctions and hence, a number of researches have been made on the therapeutic effect of this molecule. Recently, mangiferin has been proved to be an effective remedy in diabetes and diabetes-related complications. It is a beneficial natural compound for type 2 diabetes mellitus as it improves insulin sensitivity, modulates lipid profile and reverts adipokine levels to normal.

Conclusion: This study concludes that mangiferin has the potential to treat diabetes and it can be developed as a therapeutic agent for diabetes and the complications caused by diabetes.

Keywords: Insulin sensitivity, natural xanthone, α-glucosidase, dyslipidemia, nephropathy, mangiferin.

[1]
Prabhakar PK, Doble M. Mechanism of action of natural products used in the treatment of diabetes mellitus. Chin J Integr Med 2011; 17(8): 563.
[http://dx.doi.org/10.1007/s11655-011-0810-3]
[2]
Holt RI, Cockram C, Flyvbjerg A, Goldstein BJ. Textbook of diabetes. 4th ed. John Wiley & Sons 2017.
[http://dx.doi.org/10.1002/9781118924853]
[3]
Rowley WR, Bezold C, Arikan Y, et al. Diabetes 2030: Insights from Yesterday, Today, and Future Trends. Popul Health Manag 2017; 20(1): 6-12.
[http://dx.doi.org/10.1089/pop.2015.0181]
[4]
Dias DA, Urban S, Roessner U. A historical overview of natural products in drug discovery. Metabolites 2012; 2(2): 303-36.
[http://dx.doi.org/10.3390/metabo2020303]
[5]
Wiechowski W. Sitzungsberichte – III. Biologische Sektion. Lotos 1908; 56: 61.
[6]
Imran M, Arshad MS, Butt MS, et al. Mangiferin: a natural miracle bioactive compound against lifestyle related disorders. Lipids Health Dis 2017; 16(1): 84.
[http://dx.doi.org/10.1186/s12944-017-0449-y]
[7]
Sekar M. Molecules of interest-mangiferin-a review. Annu Res Rev Biol 2015; 5(4): 307-20.
[http://dx.doi.org/10.9734/ARRB/2015/12669]
[8]
Benard O, Chi Y. Medicinal properties of mangiferin, structural features, derivative synthesis, pharmacokinetics and biological activities. Mini Rev Med Chem 2015; 15(7): 582-94.
[http://dx.doi.org/10.2174/1389557515666150401111410]
[9]
Fujita M, Inoue T. Biosynthesis of mangiferin in Anemarrhena asphodeloides Bunge. I. The origin of the xanthone nucleus. Chem Pharm Bull (Tokyo) 1980; 28: 2476-81.
[http://dx.doi.org/10.1248/cpb.28.2476]
[10]
Fujita M, Inoue T. Biosynthesis of Mangiferin in Anemarrhena asphodeloides BUNGE. II. C-Glucosylation of Mangiferin. Chem Pharm Bull (Tokyo) 1980; 28(8): 2482-6.
[http://dx.doi.org/10.1248/cpb.28.2482]
[11]
Wu Z, Wei G, Lian G, Yu B. Synthesis of mangiferin, isomangiferin, and homomangiferin. J Org Chem 2010; 75(16): 5725-8.
[http://dx.doi.org/10.1021/jo100776q]
[12]
Pokorski M, Poździk M, Mazzatenta A. Antioxidant treatment for impaired hypoxic ventilatory responses in experimental diabetes in the rat. Respir Physiol Neurobiol 2018; 255: 30-8.
[http://dx.doi.org/10.1016/j.resp.2018.05.005]
[13]
Ichiki H, Miura T, Kubo M, et al. New antidiabetic compounds, mangiferin and its glucoside. Biol Pharm Bull 1998; 21(12): 1389-90.
[http://dx.doi.org/10.1248/bpb.21.1389]
[14]
Miura T, Ichiki H, Iwamoto N, et al. Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside. Biol Pharm Bull 2001; 24(9): 1009-11.
[http://dx.doi.org/10.1248/bpb.24.1009]
[15]
Miura T, Iwamoto N, Kato M, et al. The suppressive effect of mangiferin with exercise on blood lipids in type 2 diabetes. Biol Pharm Bull 2001; 24(9): 1091-2.
[http://dx.doi.org/10.1248/bpb.24.1091]
[16]
Sellamuthu PS, Muniappan BP, Perumal SM, Kandasamy M. Antihyperglycemic effect of mangiferin in streptozotocin induced diabetic rats. J Health Sci 2009; 55(2): 206-14.
[http://dx.doi.org/10.1248/jhs.55.206]
[17]
Muruganandan S, Srinivasan K, Gupta S, et al. Effect of mangiferin on hyperglycemia and atherogenicity in streptozotocin diabetic rats. J Ethnopharmacol 2005; 97(3): 497-501.
[http://dx.doi.org/10.1016/j.jep.2004.12.010]
[18]
Dineshkumar B, Mitra A, Manjunatha M. Studies on the anti-diabetic and hypolipidemic potentials of mangiferin (xanthone glucoside) in streptozotocin-induced Type 1 and Type 2 diabetic model rats. Int J Adv Pharm Sci 2010; 1(1): 75-85.
[19]
Gu PC, Wang L, Han MN, et al. Comparative pharmacokinetic study of mangiferin in normal and alloxan-induced diabetic rats after oral and intravenous administration by UPLC-MS/MS. Pharmacology 2019; 103(1-2): 30-7.
[http://dx.doi.org/10.1159/000493364]
[20]
Vo THT, Nguyen TD, Nguyen QH, Ushakova NA. Extraction of mangiferin from the leaves of the mango tree mangifera indica and evaluation of its biological activity in terms of blockade of α-glucosidase. Pharm Chem J 2017; 51(9): 806-10.
[http://dx.doi.org/10.1007/s11094-017-1697-x]
[21]
Picot MC, Zengin G, Mollica A, et al. In vitro and in silico studies of mangiferin from Aphloia theiformis on key enzymes linked to diabetes type 2 and associated complications. Med Chem 2017; 13(7): 633-40.
[http://dx.doi.org/10.2174/1573406413666170307163929]
[22]
Ganogpichayagrai A, Palanuvej C, Ruangrungsi N. Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves. J Adv Pharm Technol Res 2017; 8(1): 19.
[http://dx.doi.org/10.4103/2231-4040.197371]
[23]
Phoboo S, Pinto MDS, Barbosa ACL, et al. Phenolic-linked biochemical rationale for the anti-diabetic properties of Swertia chirayita (Roxb. ex Flem.) Karst. Phytother Res 2013; 27(2): 227-35.
[http://dx.doi.org/10.1002/ptr.4714]
[24]
Thitikornpong W, Palanuvej C, Ruangrungsi N. In vitro antidiabetic, antioxidation and cytotoxicity activities of ethanolic extract of Aquilaria crassna leaves and its active compound; mangiferin. Indian J Tradit Knowl 2019; 18(1): 144-50.
[25]
Sellamuthu PS, Arulselvan P, Muniappan BP, Kandasamy M. Effect of mangiferin isolated from Salacia chinensis regulates the kidney carbohydrate metabolism in streptozotocin–induced diabetic rats. Asian Pac J Trop Biomed 2012; 2(3): S1583-7.
[http://dx.doi.org/10.1016/S2221-1691(12)60457-2]
[26]
Singh AK, Raj V, Keshari AK, et al. Isolated mangiferin and naringenin exert antidiabetic effect via PPARγ/GLUT4 dual agonistic action with strong metabolic regulation. Chem Biol Interact 2018; 280: 33-44.
[http://dx.doi.org/10.1016/j.cbi.2017.12.007]
[27]
Miura T, Iwamoto N, Kato M, et al. Effect of Mangiferin on muscle GLUT4 protein content in TSOD (Tsumura, Suzuki, Obese, Diabetes) mouse, new type 2 diabetic mice. Biomed Res 2001; 22(5): 249-52.
[http://dx.doi.org/10.2220/biomedres.22.249]
[28]
Suryavanshi SV, Kulkarni YA. NF-κβ: A potential target in the management of vascular complications of diabetes. Front Pharmacol 2017; 8: 798.
[http://dx.doi.org/10.3389/fphar.2017.00798]
[29]
Sellamuthu PS, Arulselvan P, Muniappan BP, et al. Mangiferin from Salacia chinensis prevents oxidative stress and protects pancreatic β-cells in streptozotocin-induced diabetic rats. J Med Food 2013; 16(8): 719-27.
[http://dx.doi.org/10.1089/jmf.2012.2480]
[30]
Muruganandan S, Gupta S, Kataria M, et al. Mangiferin protects the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats. Toxicology 2002; 176(3): 165-73.
[http://dx.doi.org/10.1016/S0300-483X(02)00069-0]
[31]
Mahali SK, Manna SK. Beta-D-glucoside protects against advanced glycation end products (AGEs)-mediated diabetic responses by suppressing ERK and inducing PPAR gamma DNA binding. Biochem Pharmacol 2012; 84(12): 1681-90.
[http://dx.doi.org/10.1016/j.bcp.2012.09.033]
[32]
Hou J, Zheng D, Fung G, et al. Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats. Can J Physiol Pharmacol 2015; 94(3): 332-40.
[http://dx.doi.org/10.1139/cjpp-2015-0073]
[33]
Wang HL, Li CY, Zhang B, et al. Mangiferin facilitates islet regeneration and β-cell proliferation through upregulation of cell cycle and β-cell regeneration regulators. Int J Mol Sci 2014; 15(5): 9016-35.
[http://dx.doi.org/10.3390/ijms15059016]
[34]
Wang H, He X, Lei T, et al. Mangiferin induces islet regeneration in aged mice through regulating p16INK4a. Int J Mol Med 2018; 41(6): 3231-42.
[http://dx.doi.org/10.3892/ijmm.2018.3524]
[35]
Saleh S, El-Maraghy N, Reda E, Barakat W. Modulation of diabetes and dyslipidemia in diabetic insulin-resistant rats by mangiferin: role of adiponectin and TNF-α. An Acad Bras Cienc 2014; 86(4): 1935-48.
[http://dx.doi.org/10.1590/0001-3765201420140212]
[36]
Suman RK, Mohanty IR, Maheshwari U, et al. Natural dipeptidyl peptidase-IV inhibitor mangiferin mitigates diabetes- and metabolic syndrome-induced changes in experimental rats. Diabetes Metab Syndr Obes 2016; 9: 261.
[http://dx.doi.org/10.2147/DMSO.S109599]
[37]
Hou B, Kuang MT, Chi XQ, et al. Natural Breviscapin, Mangiferin, and a Modified Mangostin Present Inhibitory Effect on Dipeptidyl Peptidase‐IV. ChemistrySelect 2018; 3(39): 10864-8.
[http://dx.doi.org/10.1002/slct.201801350]
[38]
Hou J, Zheng D, Fan K, et al. Combination of mangiferin and dipeptidyl peptidase-4 inhibitor sitagliptin improves impaired glucose tolerance in streptozotocin-diabetic rats. Pharmacology 2012; 90(3-4): 177-82.
[http://dx.doi.org/10.1159/000342128]
[39]
Liu YW, Cheng YQ, Liu XL, et al. Mangiferin upregulates glyoxalase 1 through activation of Nrf2/are signaling in central neurons cultured with high glucose. Mol Neurobiol 2017; 54(6): 4060-70.
[http://dx.doi.org/10.1007/s12035-016-9978-z]
[40]
Huang TH, He L, Qin Q, et al. Salacia oblonga root decreases cardiac hypertrophy in Zucker diabetic fatty rats: inhibition of cardiac expression of angiotensin II type 1 receptor. Diabetes Obes Metab 2008; 10(7): 574-85.
[http://dx.doi.org/10.1111/j.1463-1326.2007.00750.x]
[41]
Hou J, Zheng D, Zhong G, Hu Y. Mangiferin mitigates diabetic cardiomyopathy in streptozotocin-diabetic rats. Can J Physiol Pharmacol 2013; 91(9): 759-63.
[http://dx.doi.org/10.1139/cjpp-2013-0090]
[42]
Suchal K, Malik S, Khan SI, et al. Protective effect of mangiferin on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats: role of AGE-RAGE/MAPK pathways. Sci Rep 2017; 7: 42027.
[http://dx.doi.org/10.1038/srep42027]
[43]
Mao X, Liu L, Cheng L, et al. Adhesive nanoparticles with inflammation regulation for promoting skin flap regeneration. J Control Release 2019; 297: 91-101.
[http://dx.doi.org/10.1016/j.jconrel.2019.01.031]
[44]
Li H, Liao H, Bao C, et al. Preparation and evaluations of mangiferin-loaded PLGA scaffolds for alveolar bone repair treatment under the diabetic condition. AAPS PharmSciTech 2017; 18(2): 529-38.
[http://dx.doi.org/10.1208/s12249-016-0536-9]
[45]
Huang THW, Peng G, Li GQ, et al. Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis in Zucker diabetic fatty rats: activation of PPAR-α. Toxicol Appl Pharmacol 2006; 210(3): 225-35.
[http://dx.doi.org/10.1016/j.taap.2005.05.003]
[46]
Li X, Cui X, Sun X, et al. Mangiferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats. Phytother Res 2010; 24(6): 893-9.
[47]
Liu YW, Zhu X, Zhang L, et al. Up-regulation of glyoxalase 1 by mangiferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats. Eur J Pharmacol 2013; 721(1-3): 355-64.
[http://dx.doi.org/10.1016/j.ejphar.2013.08.029]
[48]
Wang X, Gao L, Lin H, et al. Mangiferin prevents diabetic nephropathy progression and protects podocyte function via autophagy in diabetic rat glomeruli. Eur J Pharmacol 2018; 824: 170-8.
[http://dx.doi.org/10.1016/j.ejphar.2018.02.009]
[49]
Guang-Kai XU, Chen-Yu SUN, Xiao-Ying QIN, et al. Effects of ethanol extract of Bombax ceiba leaves and its main constituent mangiferin on diabetic nephropathy in mice. Chin J Nat Med 2017; 15(8): 597-605.
[50]
He L, Qi Y, Rong X, et al. The Ayurvedic medicine Salacia oblonga attenuates diabetic renal fibrosis in rats: suppression of angiotensin II/AT1 signaling. Evid Based Complement Alternat Med 2011; 2011807451
[http://dx.doi.org/10.1093/ecam/nep095]
[51]
Zhu X, Cheng YQ, Du L, et al. Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in diabetic rats. Phytother Res 2015; 29(2): 295-302.
[http://dx.doi.org/10.1002/ptr.5254]
[52]
Sellamuthu PS, Arulselvan P, Muniappan BP, et al. Influence of mangiferin on membrane bound phosphatases and lysosomal hydrolases in streptozotocin induced diabetic rats. Lat Am J Pharm 2012; 31: 1013-20.
[53]
Liu YW, Zhu X, Yang QQ, et al. Suppression of methylglyoxal hyperactivity by mangiferin can prevent diabetes-associated cognitive decline in rats. Psychopharmacology (Berl) 2013; 228(4): 585-94.
[http://dx.doi.org/10.1007/s00213-013-3061-5]
[54]
Prado Y, Merino N, Acosta J, et al. Acute and 28-day subchronic toxicity studies of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark. J Pharm Pharmacogn Res 2015; 3(1): 13-23.
[55]
Arozal W, Suyatna FD, Juniantito V, et al. The Effects of Mangiferin (Mangifera indica L) in Doxorubicin-induced Cardiotoxicity in Rats. Drug Res (Stuttg) 2015; 65(11): 574-80.
[56]
Nishigaki I, Venugopal R, Sakthisekaran D, Rajkapoor B. In vitro protective effect of mangiferin against glycated protein-iron chelate induced toxicity in human umbilical vein endothelial cells. J Biol Sci 2007; 7(7): 1227-32.
[http://dx.doi.org/10.3923/jbs.2007.1227.1232]


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Article Details

VOLUME: 16
ISSUE: 7
Year: 2020
Published on: 23 July, 2020
Page: [690 - 698]
Pages: 9
DOI: 10.2174/1573399815666191004112023
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