Mangiferin: the miraculous xanthone with diverse pharmacological properties.

Tusheema Dutta, Tuyelee Das, Abilash Valsala Gopalakrishnan, Suchismita Chatterjee Saha, Mimosa Ghorai, Samapika Nandy, Manoj Kumar, Arabinda Ghosh, Nobendu Mukerjee, Abhijit Dey
Author Information
  1. Tusheema Dutta: Vanasiri Evolutionary Ecology Lab, School of Biology, IISER Thiruvananthapuram, Maruthamala, Vithura, Kerala, 695551, India.
  2. Tuyelee Das: Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700073, West Bengal, India.
  3. Abilash Valsala Gopalakrishnan: Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India.
  4. Suchismita Chatterjee Saha: Department of Zoology, Nabadwip Vidyasagar College, Nabadwip, West Bengal, India.
  5. Mimosa Ghorai: Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700073, West Bengal, India.
  6. Samapika Nandy: Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700073, West Bengal, India.
  7. Manoj Kumar: Chemical and Biochemical Processing Division, ICAR-Central Institute for Research on Cotton Technology, Mumbai, Maharashtra, India.
  8. Radha: School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India.
  9. Arabinda Ghosh: Department of Botany, Gauhati University, Assam, India.
  10. Nobendu Mukerjee: Department of Health Sciences, Novel Global Community Educational Foundation, Hebarsham, Australia.
  11. Abhijit Dey: Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata, 700073, West Bengal, India. abhijit.dbs@presiuniv.ac.in.

Abstract

Mangiferin (1,3,6,7-tetrahydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] xanthen-9-one) is a bioactive component derived primarily from the mango tree. Belonging to the Xanthone family, its structure allows it to engage with a variety of pharmacological targets. The symmetric linked core of xanthones has a heterogeneous biogenetic background. The carbon atoms are designated in a biochemical order, which reveals the reason of ring A (C1-C4) being referred to as acetate originated, and ring B (C5-C8) is referred to as shikimate originated. The antibacterial, hypocholesterolemic, antiallergic, cardiotonic, antidiabetic, anti-neoplastic, neuroprotective, antioxidant and immunomodulatory properties have all been demonstrated for the secondary metabolite. This study assessed and explained the important medical properties of mangiferin available in published literature, as well as its natural source, biosynthesis, absorption and bioavailability; multiple administration routes; metabolism; nanotechnology for enhanced efficacy of mangiferin and its toxicity, to aid the anticipated on-going potential of mangiferin as a novel diagnostic treatment.

Keywords

References

  1. Abdul-Muneer PM, Chandra N, Haorah J (2015) Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury. Mol Neurobiol 51:966–979 [DOI: 10.1007/s12035-014-8752-3]
  2. Aderibigbe AO, Emudianughe TS, Lowal BA (2001) Evaluation of antidiabetic action of Mangifera indica in mice. Phytother Res 15:456–458 [DOI: 10.1002/ptr.859]
  3. Aritomi M, Kawasaki T (1969) A new xanthone C-glucoside, position isomer of mangiferin, from Anemarrhena asphodeloides Bunge. Tetrahedron Lett 10(12):941–944 [DOI: 10.1016/S0040-4039(01)97704-4]
  4. Arozal W, Suyatna FD, Juniantito V, Rosdiana DS, Amurugam S, Aulia R ... Siswandi R (2015) The effects of mangiferin (Mangifera indica L) in doxorubicin-induced cardiotoxicity in rats. Drug Res 65(11): 574-580
  5. Bairy I, Reeja S, Rao PS, Bhat M, Shivananda PG (2002) Evaluation of antibacterial activity of Mangifera indica on anaerobic dental microglora based on in vivo studies. Indian J Pathol Microbiol 45(3):307–310
  6. Bera S, Chaudhuri S, Dutta D (2015) Assessment of free-radical scavenging activities of mangiferin from Curcuma amada obtained by non-conventional extraction methods: a comparative study. Indian J Biotechnol 14:179–185
  7. Bhatia VK, Seshadri TR (1968) Synthesis of mangiferin. Tetrahedron Lett 14:1741–1742 [DOI: 10.1016/S0040-4039(01)99040-9]
  8. Bhattacharya SK, Sanyal AK, Ghosal S (1972) Monoamine oxidase-inhibiting activity of mangiferin isolated from Canscora decussate. Naturwissenschaften 59:651 [DOI: 10.1007/BF00609562]
  9. Bhattacharyya S, Ahmmed SM, Saha BP, Mukherjee PK (2014) Soya phospholipid complex of mangiferin enhances its hepatoprotectivity by improving its bioavailability and pharmacokinetics. J Sci Food Agric 94:1380–1388 [DOI: 10.1002/jsfa.6422]
  10. Braune A, Engst W, Blaut M (2016) Identification and functional expression of genes encoding flavonoid O- and C-glycosidases in intestinal bacteria. Environ Microbiol 18(7):2117–2129 [DOI: 10.1111/1462-2920.12864]
  11. Burmeister DM, Gomez BI, Dubick MA (2017) Molecular mechanisms of trauma-induced acute kidney injury: inflammatory and metabolic insights from animal models. Biochim Biophys Acta 1863:2661–2671 [DOI: 10.1016/j.bbadis.2017.04.011]
  12. Chakrabarti DK, Singh A, Singh K (1990) Physiological and biochemical changes induced by accumulated mangiferin in Mangifera indica. J Hortic Sci 65(6):731–737 [DOI: 10.1080/00221589.1990.11516115]
  13. Chattopadhyay T, Boucherle JX (1987) Neutron diffraction study on the structural phase transition in GeTe. J Phys C Solid State Phys 20(10):1431 [DOI: 10.1088/0022-3719/20/10/012]
  14. Chattopadhyay U, Chaudhuri L, Ghosal S (1986) Immunostimulatory activity of mangiferin, a naturally occurring xanthone-c-glucoside. Pharm Res 3(5):307–308 [DOI: 10.1023/A]
  15. Chi XJ, Meng JJ, Lin CY, Su QS, Qin YY, Wei RH, Lan D, Huang C (2021) Mangiferin inhibits human lung adenocarcinoma by suppressing MiR-27b and MiR-92a. Evid. Based Complement Alternat Med 13:2021
  16. da Cruz Jr JW, de Moraes LR, dos Santos MH, da Silva GA, Brigagão MR, Ellena J, Doriguetto AC (2008) Crystalline structure of mangiferin, a C-glycosyl-substituted 9H-xanthen-9-one isolated from the stem bark of Mangifera indica. Helv Chim Acta 91(1):144–154 [DOI: 10.1002/hlca.200890005]
  17. Deng Q, Tian YX, Liang J (2018) Mangiferin inhibits cell migration and invasion through Rac1/WAVE2 signalling in breast cancer. Cytotechnology 70(2):593–601 [>PMCID: ]
  18. Dong M, Li L, Li G, Song J, Liu B, Liu X, Wang M (2020) Mangiferin protects against alcoholic liver injury via suppression of inflammation-induced adipose hyperlipolysis. Food Funct 11(10):8837–8851 [DOI: 10.1039/D0FO01436B]
  19. Du M, Wen G, Jin J, Chen Y, Cao J, Xu A (2018) Mangiferin prevents the growth of gastric carcinoma by blocking the PI3K-Akt signalling pathway. Anticancer Drugs 29(2):167–175 [DOI: 10.1097/CAD.0000000000000583]
  20. Emeka PM, Badger-Emeka LI, Ibrahim HI, Thirugnanasambantham K, Hussen J (2020) Inhibitory potential of mangiferin on glucansucrase producing Streptococcus mutans biofilm in dental plaque. Appl Sci 10(22):8297 [DOI: 10.3390/app10228297]
  21. Faizi S, Zikr-ur-Rehman S, Ali M, Naz A (2006) Temperature and solvent dependent NMR studies on mangiferin and complete NMR spectral assignments of its acyl and methyl derivatives. Magn Reson Chem 44(9):838–844 [DOI: 10.1002/mrc.1854]
  22. Finnegan RA, Stephani RA, Ganguli G, Ganguly SN, Bhattacharya AK (1968) Occurrence of mangiferin in Hiptage madablota Geartn. J Pharm Sci 57(6):1039–1040 [DOI: 10.1002/jps.2600570631]
  23. Fu Y, Liu H, Song C, Zhang F, Liu Y, Wu J, Wen X, Liang C, Ma K, Li L et al (2015) Mangiferin regulates cognitive deficits and heme oxygenase-1 induced by lipopolysaccharide in mice. Int Immunopharmacol 29:950–956 [DOI: 10.1016/j.intimp.2015.10.035]
  24. Fujiwara N, Som AT, Pham LD, Lee BJ, Mandeville ET, Lo EH, Arai K (2016) A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model. Neurosci Lett 633:7–13 [>PMCID: ]
  25. Geodakyan SV, Voskoboinikova IV, Kolesnik JA, Tjukavkina NA, Vasiliy LI, Glyzin VI (1992a) High-performance liquid chromatographic method for the determination of mangiferin, likviritin and dihydroquercetin in rat plasma and urine. J Chromatogr B Biomed Sci Appl 577(2):371–375 [DOI: 10.1016/0378-4347(92)80262-O]
  26. Geodakyan SV, Voskoboinikova IV, Tjukavkina NA, Kolhir VK, Kolesnik YA, Zjuzin VA, Glyzin VI, Sokolov SJ (1992b) Experimental pharmacokinetics of biologically active plant phenolic compounds. I. Pharmacokinetics of mangiferin in the rat. Phytother Res 6(6):332–334 [DOI: 10.1002/ptr.2650060611]
  27. Ghosal S, Sharma PV, Chaudhuri RK, Bhattacharya SK (1973) Chemical constituents of the gentianaceae V: Tetraoxygenated xanthones of Swertia chirata buch.-ham. J Pharm Sci 62:926–930 [DOI: 10.1002/jps.2600620614]
  28. Gold-Smith F, Fernandez A, Bishop K (2016) Mangiferin and cancer: mechanisms of action. Nutrients 8(7):396 [>PMCID: ]
  29. Gong X, Zhang Li, Jiang R, Ye M, Yin X, Wan J (2013) Anti-inflammatory effects of mangiferin on sepsis-induced lung injury in mice via up-regulation of heme oxygenase-1. J Nutr Biochem 24(6):1173–1181 [DOI: 10.1016/j.jnutbio.2012.09.003]
  30. Gu PC, Wang L, Han MN, Peng J, Shang JC, Pan YQ, Han WL (2019) Comparative pharmacokinetic study of mangiferin in normal and alloxan-induced diabetic rats after oral and intravenous administration by UPLC-MS/MS. Pharmacology 103(1–2):30–37 [DOI: 10.1159/000493364]
  31. Guha S, Ghosal S, Chattopadhyay U (1996) Antitumor, immunomodulatory and anti-HIV effect of mangiferin, a naturally occurring glucosylxanthone. Chemotherapy 42:443–451 [DOI: 10.1159/000239478]
  32. Guo X, Cheng M, Hu P, Shi Z, Chen S, Liu H, Shi H, Xu Z, Tian X, Huang C (2018) Absorption, metabolism, and pharmacokinetics profiles of norathyriol, an aglycone of mangiferin, in rats by HPLC-MS/MS. J Agric Food Chem 66(46):12227–12235 [DOI: 10.1021/acs.jafc.8b03763]
  33. Guo H, Chen M, Li M, Hu M, Chen B, Zhou C (2019) Pharmacokinetic comparisons of mangiferin and mangiferin monosodium salt in rat plasma by UPLC-MS/MS. J Chem 14:2019
  34. Han S, Mao H, Dally WJ (2015) Deep compression: compressing deep neural networks with pruning, trained quantization and huffman coding. arXiv preprint arXiv:151000149
  35. Hattori M, Shu Y, Tomimori T, Kobashi K, Namba T (1989) Phytochemistry 28:1289–1290 [DOI: 10.1016/0031-9422(89)80239-0]
  36. He L et al (2014) Mangiferin attenuate sepsis-induced acute kidney injury via antioxidant and anti-inflammatory effects. Am J Nephrol 40(5):441–450 [DOI: 10.1159/000369220]
  37. He Q, Ai J, Huang Y (2014) Relationship between endothelial damage and p120-catenin in paraquat intoxication and the protective effect of mangiferin. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 26:369–373
  38. He W, You Y, Du S, Lei T, Wang H, Li X, He X, Tong R, Wang Y (2019) Anti-neoplastic effect of mangiferin on human ovarian adenocarcinoma OVCAR8 cells via the regulation of YAP. Oncol Lett 17(1):1008–1018
  39. Hou S, Wang F, Li Y, Li Y, Wang M, Sun D, Sun C (2012) Pharmacokinetic study of mangiferin in human plasma after oral administration. Food Chem 132(1):289–294 [DOI: 10.1016/j.foodchem.2011.10.079]
  40. Hou J, Zheng D, Zhong G, Hu Y (2013) Mangiferin mitigates diabetic cardiomyopathy in streptozotocin-diabetic rats. Can J Physiol Pharmacol 91(9):759–763 [DOI: 10.1139/cjpp-2013-0090]
  41. Huang H, Tan Z, Deng J, Liang Q, Nong Y, Song N (2011) Metabolism of mangiferin by human intestinal bacteria in vitro. Zhongguo Zhong Yao za Zhi= Zhongguo Zhongyao Zazhi= China Journal of Chinese Materia. Medica 36(4):443–445
  42. Jahurul MHA et al (2015) Mango (Mangifera indica L.) by-products and their valuable components: A review. Food Chem 183:173–180 [DOI: 10.1016/j.foodchem.2015.03.046]
  43. Jangra A, Lukhi MM, Sulakhiya K, Baruah CC, Lahkar M (2014) Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice. Eur J Pharmacol 740:337–347 [DOI: 10.1016/j.ejphar.2014.07.031]
  44. Ji D, Qiu JC, Su XN, Qin YW, Hao M, Li L, Lu TL, Li XK, Jiang CX (2019) Study on pharmacokinetics and tissues distribution of neomangiferin, mangiferin, timosaponin BII, Timosaponin BIII, and timosaponin AIII after oral administration of Anemarrhenae rhizoma extract in rats. Pharmacogn Mag 15(65):557 [DOI: 10.4103/pm.pm_65_19]
  45. Jiang T, Han F, Gao G, Liu M (2020) Mangiferin exert cardioprotective and anti-apoptotic effects in heart failure induced rats. Life Sci 249:117476 [DOI: 10.1016/j.lfs.2020.117476]
  46. Kaliappan I, Kammala AK, Ramasamy MK, Dubey GP (2015) Structural elucidation of possible metabolic profile of mangiferin by oral and intraperitoneal administration. J Pharm Drug Deliv Res 4:1–2
  47. Kammalla AK, Ramasamy MK, Inampudi J, Dubey GP, Agrawal A, Kaliappan I (2015) Comparative pharmacokinetic study of mangiferin after oral administration of pure mangiferin and US patented polyherbal formulation to rats. AAPS PharmSciTech 16(2):250–258 [DOI: 10.1208/s12249-014-0206-8]
  48. Khare P, Shanker K (2016) Mangiferin: a review of sources and interventions for biological activities. BioFactors 42(5):504–514 [DOI: 10.1002/biof.1308]
  49. Khurana RK, Gaspar BL, Welsby G, Katare OP, Singh KK, Singh B (2018) Improving the biopharmaceutical attributes of mangiferin using vitamin E-TPGS co-loaded self-assembled pho- sholipidic nano-mixed micellar systems. Drug Deliv Transl Res 8(3):617–32 [>PMCID: ]
  50. Lai L, Lin LC, Lin JH, Tsai TH (2003) Pharmacokinetic study of free mangiferin in rats by microdialysis coupled with microbore high-performance liquid chromatography and tandem mass spectrometry. J Chromatogr A 987(1–2):367–374 [DOI: 10.1016/S0021-9673(02)01415-2]
  51. Lewén A, Matz P, Chan PH (2000) Free radical pathways in CNS injury. J Neurotrauma 17:871–890 [DOI: 10.1089/neu.2000.17.871]
  52. Li YJ, Sui YJ, Dai YH, Deng YL (2008) LC determination and pharmacokinetics study of mangiferin in rat plasma and tissues. Chromatographia 67:957–960 [DOI: 10.1365/s10337-008-0612-8]
  53. Li H, Huang J, Yang B, Xiang T, Yin X, Peng W, Ren G (2013) Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway. Toxicol Appl Pharmacol 272(1):180–190 [DOI: 10.1016/j.taap.2013.05.011]
  54. Li M, Ma H, Yang L, Li P (2016) Mangiferin inhibition of proliferation and induction of apoptosis in human prostate cancer cells is correlated with downregulation of B-cell lymphoma-2 and upregulation of microRNA-182. Oncol Lett 11(1):817–822 [DOI: 10.3892/ol.2015.3924]
  55. Lim J, Liu Z, Apontes P, Feng D, Pessin JE, Sauve AA, Angeletti RH, Chi Y (2014) Dual mode action of mangiferin in mouse liver under high fat diet. PLoS ONE 9(3):e90137 [>PMCID: ]
  56. Lin A, Li J, Li D, Jin H, Liu Y (2019) Tissue distribution study of mangiferin after intragastric administration of mangiferin monomer, Rhizoma Anemarrhenae, and Rhizoma Anemarrhenae-Phellodendron decoctions in normal or type 2 diabetic rats by LC-MS/MS. J Chromatogr B 1122:18–28 [DOI: 10.1016/j.jchromb.2019.05.019]
  57. Liu H, Wu B, Pan G, He L, Li Z, Fan M, Jian L, Chen M, Wang K, Huang C (2012) Metabolism and pharmacokinetics of mangiferin in conventional rats, pseudo-germ-free rats, and streptozotocin-induced diabetic rats. Drug Metab Dispos 40(11):2109–2118 [DOI: 10.1124/dmd.112.045849]
  58. Luo F, Lv Q, Zhao Y, Hu G, Huang G, Zhang J, Sun C, Li X, Chen K (2012) Quantification and purification of mangiferin from Chinese Mango (Mangifera indica L.) cultivars and its protective effect on human umbilical vein endothelial cells under H(2)O(2)-induced stress. Int J Mol Sci. 13:11260–11274 [>PMCID: ]
  59. Lwin OM, Giribabu N, Kilari EK, Salleh N (2021) Topical administration of mangiferin promotes healing of the wound of streptozotocin-nicotinamide-induced type-2 diabetic male rats. J Dermatol Treat 32(8):1039–1048 [DOI: 10.1080/09546634.2020.1721419]
  60. Ma H, Chen H, Sun L, Tong L, Zhang T (2014) Improving permeability and oral absorption of mangiferin by phospholipid complexation. Fitoterapia 1(93):54–61 [DOI: 10.1016/j.fitote.2013.10.016]
  61. Maji HS, Maji S, Roy R, Sen A, Biswas T (2015) Isolation of mangiferin from flowering buds of mangifera indica l and its evaluation of in vitro antibacterial activity. JPA 4:49–56
  62. Márquez L, García-Bueno B, Madrigal JL, Leza JC (2012) Mangiferin decreases inflammation and oxidative damage in rat brain after stress. Eur J Nutr 51:729–739 [DOI: 10.1007/s00394-011-0252-x]
  63. Mazlan NA, Azman S, Ghazali NF, Yusri PZ, Idi HM, Ismail M, Sekar M (2019) Synergistic antibacterial activity of mangiferin with antibiotics against Staphylococcus aureus. Drug Invention Today 16(12):14–17
  64. Mei S, Perumal M, Battino M, Kitts DD, Xiao J, Ma H, Chen X (2021) Mangiferin: a review of dietary sources, absorption, metabolism, bioavailability, and safety. Crit Rev Food Sci Nutr 21:1–9 [DOI: 10.1080/10408398.2021.1983767]
  65. Mittal S, Iqubal MK, Iqbal B, Gupta MM, Ali J, Baboota S (2021) A pervasive scientific overview on mangiferin in the prevention and treatment of various diseases with preclinical and clinical updates. J Complement Integr Med 18(1):9–21 [DOI: 10.1515/jcim-2019-0250]
  66. Miura T, Ichiki H, Hashimoto I, Iwamoto N, Kao M, Kubo M, Ishihara E et al (2001) Antidiabetic activity of a xanthone compound, mangiferin. Phytomedicine 8(2):85–87 [DOI: 10.1078/0944-7113-00009]
  67. Miura T, Ichiki H, Iwamoto N, Kato M, Kubo M, Sasaki H, Okada M, Ishida T, Seino Y, Tanigawa K (2001) Antidiabetic activity of the rhizoma of Anemarrhena asphodeloides and active components, mangiferin and its glucoside. Biol Pharm Bull 24:1009–1011 [DOI: 10.1248/bpb.24.1009]
  68. Mukherjee SK (1972) Origin of mango (Mangifera indica). Econ Bot 26:260–264. https://doi.org/10.1007/BF02861039 [DOI: 10.1007/BF02861039]
  69. Muruganandan S, Gupta S, Kataria M, Lal J, Gupta PK (2002) Mangiferin protects the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats. Toxicology 176(3):165–173 [DOI: 10.1016/S0300-483X(02)00069-0]
  70. Muruganandan S, Srinivasan K, Gupta S, Gupta PK, Lal J (2005) Effect of mangiferin on hyperglycemia and atherogenicity in streptozotocin diabetic rats. J Ethnopharmacol 97(3):497–501 [DOI: 10.1016/j.jep.2004.12.010]
  71. Namngam C, Pinsirodom P (2017) Antioxidant properties, selected enzyme inhibition capacities, and a cosmetic cream formulation of Thai mango seed kernel extracts. Trop J Pharm Res 16(1):9–16 [DOI: 10.4314/tjpr.v16i1.3]
  72. Nott PE, Roberts JC (1967) The structure of mangiferin. Phytochemistry 6(5):741–747 [DOI: 10.1016/S0031-9422(00)86015-X]
  73. Pal PB, Sinha K, Sil PC (2013) Mangiferin a natural xanthone, protects murine liver in Pb (II) induced hepatic damage and cell death via MAP kinase, NF-κB and mitochondria dependent pathways. PloS one 8(2):e56894 [>PMCID: ]
  74. Pal PB, Sinha K, Sil PC (2014) Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFα related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats. PloS one 9(9):e107220 [>PMCID: ]
  75. Pan C-W, Pan Z-Z, Jian-jian Hu, Chen W-L, Zhou G-Y, Lin W, Jin L-X, Chang-long Xu (2016) Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. Eur J Pharmacol 770:85–91 [DOI: 10.1016/j.ejphar.2015.12.006]
  76. Peng S, Hou Y, Yao J, Fang J (2019) Neuroprotection of mangiferin against oxidative damage via arousing Nrf2 signaling pathway in PC12 cells. BioFactors 45(3):381–392 [DOI: 10.1002/biof.1488]
  77. Prabhu S, Jainu M, Sabitha KE, Devi CS (2006a) Role of mangiferin on biochemical alterations and antioxidant status in isoproterenol-induced myocardial infarction in rats. J Ethnopharmacol 107:126–133 [DOI: 10.1016/j.jep.2006.02.014]
  78. Prabhu S, Jainu M, Sabitha KE, Devi CS (2006b) Cardioprotective effect of mangiferin on isoproterenol induced myocardial infarction in rats
  79. Rajendran P, Ekambaram G, Sakthisekaran D (2008) Effect of mangiferin on benzo (a) pyrene induced lung carcinogenesis in experimental Swiss albino mice. Nat Prod Res 22(8):672–680 [DOI: 10.1080/14786410701824973]
  80. Rajendran P, Jayakumar T, Nishigaki I, Ekambaram G, Nishigaki Y, Vetriselvi J, Sakthisekaran D (2013) Immunomodulatory effect of mangiferin in experimental animals with benzo (a) pyrene-induced lung carcinogenesis. International Journal of Biomedical Science: IJBS 9(2):68 [>PMCID: ]
  81. Reddeman R, Glávits R, Endres J, Clewell A, Hirka G, Vertesi A, Beres E, Szakonyiné I (2019) A toxicological evaluation of mango leaf extract ( Mangifera indica ) containing 60% mangiferin. J Toxicol 1–14. https://doi.org/10.1155/2019/4763015,2019
  82. Ren Y, Wei B, Song X, An N, Zhou Y, Jin X, Zhang Y (2015) Edaravone’s free radical scavenging mechanisms of neuroprotection against cerebral ischemia: Review of the literature. Int J Neurosci 125:555–565 [DOI: 10.3109/00207454.2014.959121]
  83. Ribeiro AC, Cunha AP, Ribeiro ME, Trevisan MT, Azul FV, Leal LK, Ricardo NM (2021) Cashew apple pectin as a carrier matrix for mangiferin: physicochemical characterization, in vitro release and biological evaluation in human neutrophils. Int J Biol Macromol 28(171):275–287 [DOI: 10.1016/j.ijbiomac.2021.01.001]
  84. Rivera DG, Hernández I, Merino N, Luque Y, Álvarez A, Martín Y, Amador A, Nuevas L, Delgado R (2011) Mangifera indica L extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma. J Pharm Pharmacol 63:1336–1345 [DOI: 10.1111/j.2042-7158.2011.01328.x]
  85. Rodeiro I, Hernandez S, Morffi J, Herrera JA, Gomez-Lechón MJ, Delgado R, Espinosa-Aguirre JJ (2012) Evaluation of genotoxicity and DNA protective effects of mangiferin, a glucosylxanthone isolated from Mangifera indica L stem bark extract. Food Chem Toxicol 50(9):3360–3366. https://doi.org/10.1016/j.fct.2012.06.032 [DOI: 10.1016/j.fct.2012.06.032]
  86. Saha S, Sadhukhan P, Sil PC (2016) Mangiferin: a xanthonoid with multipotent anti-inflammatory potential. BioFactors 42:459–474 [DOI: 10.1002/biof.1292]
  87. Sahu AK et al (2019) Mangiferin attenuates cisplatin-induced acute kidney injury in rats mediating modulation of MAPK pathway. Mol Cell Biochem 452(1–2):141–152 [DOI: 10.1007/s11010-018-3420-y]
  88. Samadarsi R, Dutta D (2019) Design and characterization of mangiferin nanoparticles for oral delivery. J Food Eng 247:80–94 [DOI: 10.1016/j.jfoodeng.2018.11.020]
  89. Samadarsi R, Dutta D (2020) Anti-oxidative effect of mangiferin-chitosan nanoparticles on oxidative stress-induced renal cells. Int J Biol Macromol 15(151):36–46 [DOI: 10.1016/j.ijbiomac.2020.02.112]
  90. Samadarsi R, Mishra D, Dutta D (2020) Mangiferin nanoparticles fortified dairy beverage as a low glycemic food product: its quality attributes and antioxidant properties. Int J Food SciTechnol 55(2):589–600 [DOI: 10.1111/ijfs.14310]
  91. Sanugul K, Akao T, Li Y, Kakiuchi N, Nakamura N, Hattori M (2005) Isolation of a human intestinal bacterium that transforms mangiferin to norathyriol and inducibility of the enzyme that cleaves a C-glucosyl bond. Biol Pharm Bull 28(9):1672–1678 [DOI: 10.1248/bpb.28.1672]
  92. Shah KA, Patel MB, Patel RJ, Parmar PK (2010) Mangifera indica (mango). Pharmacogn Rev 4(7):42 [>PMCID: ]
  93. Shang HS, Chen CJ, Shih YL, Peng SF, Chen YL, Liu KC, Huang HC, Hsueh SC, Chen KW, Lu HF, Lee MH (2021) Mangiferin induces immune responses and evaluates the survival rate in WEHI-3 cell generated mouse leukemia in vivo. Environ Toxicol 36(1):77–85 [DOI: 10.1002/tox.23013]
  94. Shi W, Deng J, Tong R, Yang Y, He X, Lv J, Wang H, Deng S, Qi P, Zhang D, Wang Y (2016) Molecular mechanisms underlying mangiferin-induced apoptosis and cell cycle arrest in A549 human lung carcinoma cells. Mol Med Rep 13(4):3423–3432 [>PMCID: ]
  95. Song W, Tang Z, Lei T, Wen X, Wang G, Zhang D, Deng M, Tang X, Chen X (2016) Stable loading and delivery of disulfiram with mPEG-PLGA/PCL mixed nanoparticles for tumor therapy. Nanomedicine NBM 12(2):377–86. https://doi.org/10.1016/j.nano.2015.10.022 [DOI: 10.1016/j.nano.2015.10.022]
  96. Song J, Meng Y, Wang M, Li L, Liu Z, Zheng K ... Li A (2020) Mangiferin activates Nrf2 to attenuate cardiac fibrosis via redistributing glutaminolysis-derived glutamate. Pharmacol Res 157: 104845
  97. Stohs SJ, Swaroop A, Moriyama H, Bagchi M, Ahmad T et al (2018) A review on antioxidant, anti-inflammatory and gastroprotective abilities of mango (Magnifera indica) leaf extract and mangiferin. J Nutr Health Sci 5(3):303
  98. Suchal K, Malik S, Gamad N, Malhotra RK, Goyal SN, Ojha S, Kumari S, Bhatia J, Arya DS (2016) Mangiferin protect myocardial insults through modulation of MAPK/TGF-β pathways. Eur J Pharmacol 776:34–43 [DOI: 10.1016/j.ejphar.2016.02.055]
  99. Talamond P, Mondolot L, Gargadennec A, de Kochko A, Hamon S, Fruchier A, Campa C (2008) First report on mangiferin (C-glucosyl-xanthone) isolated from leaves of a wild coffee plant, Coffea pseudozanguebariae (Rubiaceae). Acta Bot Gall 155(4):513–519 [DOI: 10.1080/12538078.2008.10516130]
  100. Thiengkaew P, Thanitwatthanasak S, Srisala S, Jittorntrum B, Chunhabundit R, Chitprasert P (2021) Response surface optimization of microfluidic formulations of nanobilosomes for enhancement of aqueous solubility, digestive stability, and cellular antioxidant activity of mangiferin. Food Chem 30(351):129315 [DOI: 10.1016/j.foodchem.2021.129315]
  101. Tian X, Xu Z, Li Z, Ma Y, Lian S, Guo X, Hu P, Gao Y, Huang C (2016) Pharmacokinetics of mangiferin and its metabolite—norathyriol, part 2: influence of UGT, CYP450, P-gp, and enterobacteria and the potential interaction in Rhizoma Anemarrhenae decoction with timosaponin B2 as the major contributor. Biofactors 42(5):545–555 [DOI: 10.1002/biof.1290]
  102. Vieira AB, Coelho LP, Insuela DB, Carvalho VF, dos Santos MH, Silva PM, Martins MA (2013) Mangiferin prevents guinea pig tracheal contraction via activation of the nitric oxide-cyclic GMP pathway. Plos One. 8:e717592013 [DOI: 10.1371/annotation/48d07c62-084f-4c46-b8cf-564ff59f1bd4]
  103. Vyas A, Syeda K, Ahmad A, Padhye S, Sarkar H, F. (2012) Perspectives on medicinal properties of mangiferin. Mini-Rev Med Chem 12(5):412–425 [DOI: 10.2174/138955712800493870]
  104. Wada H, Shimizu Y, Tanaka N, Cambie RC, Braggins JE (1995) Chemical and chemotaxonomical studies of ferns. LXXXVII. Constituents of Trichomanes reniforme. Chem Pharm Bull 43(3):461–465 [DOI: 10.1248/cpb.43.461]
  105. Wang RR, Gao YD, Ma CH, Zhang XJ, Huang CG, Huang JF, Zheng YT (2011) Mangiferin, an anti-HIV-1 agent targeting protease and effective against resistant strains. Molecules 16(5):4264–4277 [>PMCID: ]
  106. Wang Z, Guo S, Wang J, Shen Y, Zhang J, Wu Q (2017) Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation. Sci Rep. 7:118832017
  107. Wei Z, Yan L, Deng J, Deng J (2011) Effects of mangiferin on MAPK signaling pathway in chronic inflammation. Zhongguo Zhong Yao Za Zhi 36(13):1798–1802
  108. Wiechowski W (1908) Phytochemical and pharmacological investigations on mangiferin. Lotos 56:61
  109. Wisutthathum S, Kamkaew N, Inchan A, Chatturong U, Paracha TU, Ingkaninan K, Wongwad E, Chootip K (2019) Extract of Aquilaria crassna leaves and mangiferin are vasodilators while showing no cytotoxicity. J Tradit Complement Med 9(4):237–242. https://doi.org/10.1016/j.jtcme.2018.09.002 [DOI: 10.1016/j.jtcme.2018.09.002]
  110. Wu Z, Wei G, Lian G, Yu B (2010) Synthesis of mangiferin, isomangiferin, and homomangiferin. J Org Chem 75(16):5725–5728. https://doi.org/10.1021/jo100776q [DOI: 10.1021/jo100776q]
  111. Yang S, Kuang Ge, Zhang L, Shengwang Wu, Zhao Z, Wang B, Yin X, Gong X, Wan J (2020) Mangiferin attenuates LPS/D-GalN-Induced acute liver injury by promoting HO-1 in kupffer cells. Front Immunol 11:285 [>PMCID: ]
  112. Yu L, Chen M, Zhang R, Jin Z (2019) Inhibition of cancer cell growth in gemcitabine-resistant pancreatic carcinoma by mangiferin involves induction of autophagy, endogenous ROS production, cell cycle disruption, mitochondrial mediated apoptosis and suppression of cancer cell migration and invasion. J Buon 24(4):1581–1586
  113. Zeng Z, Lin C, Wang S, Wang P, Xu W, Ma W, Liu H (2020) Suppressive activities of mangiferin on human epithelial ovarian cancer. Phytomedicine 76:153267 [DOI: 10.1016/j.phymed.2020.153267]
  114. Zeng Z, Lin C, Wang S, Wang P, Xu W, Ma W, Wang J et al (2020) Suppressive activities of mangiferin on human epithelial ovarian cancer. Phytomedicine 76:153267 [DOI: 10.1016/j.phymed.2020.153267]
  115. Zheng MS, Lu ZY (1990) Antiviral effect of mangiferin and isomangiferin on herpes simplex virus. Chin Med J 103(2):160–165
  116. Zheng D, Hou J, Xiao Y, Zhao Z, Chen L (2012) Cardioprotective effect of mangiferin on left ventricular remodeling in rats. Pharmacology 90(1–2):78–87 [DOI: 10.1159/000339450]
  117. Zhu XM, Song JX, Huang ZZ, Wu YM, Yu MJ (1993) Antiviral activity of mangiferin against herpes simplex virus type 2 in vitro. Zhongguo yao li xue bao=Acta Pharmacol Sin 14(5):452–454
  118. Zhu X, Cheng Y-Q, Lei Du, Li Yu, Zhang F, Guo H, Liu Y-W, Yin X-X (2015) Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in diabetic rats. Phytother Res 29(2):295–302 [DOI: 10.1002/ptr.5254]
  119. Zou B, Wang H, Liu Y, Qi P, Lei T, Sun M, Wang Y (2017) Mangiferin induces apoptosis in human ovarian adenocarcinoma OVCAR3 cells via the regulation of Notch3. Oncol Rep 38(3):1431–1441 [>PMCID: ]

MeSH Term

Xanthones
Hypoglycemic Agents
Plant Extracts
Mangifera

Chemicals

xanthone
mangiferin
shikimate
Xanthones
Hypoglycemic Agents
Plant Extracts

Word Cloud

Created with Highcharts 10.0.0propertiesmangiferinMangiferinpharmacologicalringreferredoriginated1367-tetrahydroxy-2-[345-trihydroxy-6-hydroxymethyloxan-2-yl]xanthen-9-onebioactivecomponentderivedprimarilymangotreeBelongingXanthonefamilystructureallowsengagevarietytargetssymmetriclinkedcorexanthonesheterogeneousbiogeneticbackgroundcarbonatomsdesignatedbiochemicalorderrevealsreasonC1-C4acetateBC5-C8shikimateantibacterialhypocholesterolemicantiallergiccardiotonicantidiabeticanti-neoplasticneuroprotectiveantioxidantimmunomodulatorydemonstratedsecondarymetabolitestudyassessedexplainedimportantmedicalavailablepublishedliteraturewellnaturalsourcebiosynthesisabsorptionbioavailabilitymultipleadministrationroutesmetabolismnanotechnologyenhancedefficacytoxicityaidanticipatedon-goingpotentialnoveldiagnostictreatmentMangiferin:miraculousxanthonediverseAnti-cancerMangiferaindicaMangoMechanismsPharmacologicalactivity

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