Effect of mangiferin isolated from Mangifera indica leaves on in vitro blood coagulation and cell migration activities
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Abstract
Background: Mangiferin, a natural compound has been reported to possess a variety of biological activities such as anticancer, anti-diabetic, antimicrobial, antioxidant, cardioprotective activities, etc. Screening on blood coagulation activity effects of mangiferin might be helpful for further activities investigation.
Objective: This study aimed to isolate mangiferin from mango leaves and evaluate its blood coagulation and anticancer activities against human lung cancer cell lines (A549 cells).
Materials and methods: Mangiferin was extracted from mango leaves and characterized by IR, NMR, and mass spectroscopic techniques. It was determined in vitro activities as follows: blood clotting time, platelet aggregation, activated partial thromboplastin time (aPTT), prothrombin time (PT), clot lysis, fibrinolysis, and cell migration assay.
Results: It was found that mangiferin had a significantly slower effect on inducing blood clots than the control group, with the coagulation value of 13.09±2.97 minutes and decreasing platelet aggregation at an inhibition percentage value of 14.1±1.2. There was significant (p<0.05) prolongation of PT and aPTT activities tested with the mangiferin at the value of 12.4±1.2 and 29.9±3.1 seconds, respectively. However, mangiferin was unable to cause fibrin clot dissolution on fibrinolysis test. Mangiferin also showed anticancer activity against A549 cells by inhibition of cell migration assay.
Conclusion: Mangiferin showed antiplatelet aggregation activity and prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) assay without fibrinolysis activity. In addition, mangiferin showed anticancer activity against A549 cells by inhibiting cell migration.
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Personal views expressed by the contributors in their articles are not necessarily those of the Journal of Associated Medical Sciences, Faculty of Associated Medical Sciences, Chiang Mai University.
References
Dahlbäck B. Blood coagulation. Lancet 2000; 355: 1627-32. doi: 10.1016/S0140-6736(00)02225-X.
Chen A, Stecker E, Warden BA. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. J Am Heart Assoc. 2020; 9(13). doi.org/10.1161/JAHA.120.017559.
Schulman S. Advantages and limitations of the new anticoagulants. J Intern Med. 2014; 275:1-11. doi: 10.1111/joim.12138.
Atanasov AG, Zotchev SB, Dirsch VM and Supuran CT. Natural products in drug discovery: advances and opportunities. Nat Rev. 2021; 20: 200-16. doi: 10.1038/s41573-020-00114-z.
Du S, Liu H, Lei T, Xie X, Wang H, He X,et al. Mangiferin: An effective therapeutic agent against several disorders (Review). Mol Med Rep. 2018; 18(6): 4775-86. doi: 10.3892/mmr.2018.9529.
Imran M, Arshad MS, Butt MS, Kwon JH, Arshad MU and Sultan MT. Mangiferin: a natural miracle bioactive compound against lifestyle related disorders. Lipids Health Dis. 2017; 1-17. doi: 10.1186/s12944-017-0449-y.
Zou B, Wang H, Liu Y, Qi P, Lei T, Sun M, Wang Y. Mangiferin induces apoptosis in human ovarian adenocarcinoma OVCAR3 cells via the regulation of Notch3. Oncol Rep. 2017; 38: 1431–41. doi: 10.3892/or.2017.5814.
Garcia-Rivera D, Hernandez R, Bougarne N, Haegeman G, Berghe W. Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cell. Cancer Lett. 2011; 305: 21-31. doi: 10.1016/j.canlet.2011.02.011.
Apontes P, Liu Z, Su K, Benard O, Youn DY, Li X, Li W, Mirza RH, Bastie CC, Jelicks LA, Pessin JE, Muzumdar RH, Sauve AA, Chi Y. Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets. Diabetes. 2014; 63(11): 3626-36. doi: 10.2337/db14-0006.
Sellamuthu PS, Arulselvan P, Muniappan BP, Fakurazi S, Kandasamy M. 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. doi: 10.1089/jmf.2012.2480.
Zhu X, Cheng Y, Du L, Li Y, Zhang F, Guo H, Liu YW, Yin X. Mangiferin attenuates renal fibrosis through down regulation of osteopontin in diabetic rats. Phyther Res. 2015; 29: 295-302. doi: 10.1002/ptr.5254.
Dineshkumar B, Mitra A, Mahadevappa M. Studies on the anti-diabetic and hypolipidemic potentials of mangiferin (Xanthone Glucoside) in streptozotocininduced Type 1 and Type 2 diabetic model rats. Int J Adv Pharm Sci. 2010; 1: 75-85. doi: 10.5138/ijaps.2010.0976.1055.01009.
Saleh S, El-Maraghy N, Reda E, Barakat W. Modulation of diabetes and dyslipidemia in diabetic insulinresistant rats by mangiferin: role of adiponectin and TNF-α. An Acad Bras Cienc. 2014; 86(4): 1935-48. doi: 10.1590/0001-3765201420140212.
Stoilova I, Jirovetz L, Stoyanova A, Krastanov A, Gargova S, Ho L. Antioxidant activity of the polyphenol mangiferin. Electron. J Environ Agric Food Chem. 2008; 7: 2706-16.
Garrido G, Gonzalez D, Delporte C, Backhouse N, Quintero G, Nunez Selles A, Morales M. Analgesic and antiinflammatory effects of Mangifera indica L. extract (Vimang). Phytother Res. 2001; 15: 18- 21. doi: 10.1002/1099-1573(200102)15:1<18::aidptr676>3.0.co;2-r.
Al-rawi A, Dulaimi H, Rawi M. Antiviral activity of mangifera extract on influenza virus cultivated in different cell cultures. J Pure Appl Microbiol. 2019; 13: 455-8. doi: 10.22207/JPAM.13.1.50.
Joshua M and Takudzwa M. Antibacterial properties of Mangifera indica on staphylococcus aureus. African J Clin Exp. 2013; 14(2): 62-74. doi: 10.4314/ajcem.v14i2.4.
Mazlan NA, Azman S, Ghazali NF, Yusri PZS, Idi HM, Ismail M, Sekar M. Synergistic antibacterial activity of mangiferin with antibiotics against Staphylococcus aureus. Drug Invent. Today 2019; 12: 14-7.
Prabhu S, Naraya SH, Shyamala CS. Mechanism of protective action of mangiferin on suppression of inflammatory response and lysosomal instability in rat model of myocardial infarction. Phytother Res. 2009; 23: 756-60. doi: 10.1002/ptr.2549.
Rasool M, Sabina EP, Mahinda PS, Gnanaselvi BC, Mangiferin, a natural polyphenol protects the hepatic damage in mice caused by CCl4 intoxication. Comp Clin Pathol. 2012; 21: 865-72. doi: 10.1007/s00580-011-1190-y.
Mei S, Perumal M, Battino M, Kitts DD, Xiao J, Chen X. Mangiferin: a review of dietary sources, absorption, metabolism, bioavailability, and safety. Crit Rev Food Sci Nutr. 2023; 63(18): 3046-64. doi: 10.1080/10408398.2021.1983767.
Singh SK, Kuar Y, Kumar SS, Sharma VK, Dua K, and Samad A. Antimicrobial Evaluation of Mangiferin Analogues. Indian J Pharm Sci. 2009; 71(3): 328-31. doi: 10.4103/0250-474X.56023.
Li M, Ma H, Yang L, Li P. 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. 2016; 11(1): 817-22. doi: 10.3892/ol.2015.3924.
Samadarsi R, Augustin L, Kumar C, and Dutta D. In-silico and in-vitro studies on the efficacy of mangiferin against colorectal cancer.BMCChem. 2022; 16(1): 42. doi: 10.1186/s13065-022-00835-9.
Peng ZG, Yao YB, Yang J, Tang YL, Huang X. Mangiferin induces cell cycle arrest at G2/M phase through ATR-Chk1 pathway in HL-60 leukemia cells. Genet Mol Res. 2015; 14: 4989-5002. doi: 10.4238/2015.May.12.2.
Shi W, Deng J, Tong R, Yang Y, He X, Wang H, Deng S, Qi P, Zhang D and Wang Y. Molecular mechanisms underlying mangiferin-induced apoptosis and cell cycle arrest in A549 human lung carcinoma cells. Mol Med Rep. 2016; 13: 3423-32. doi: 10.3892/mmr.2016.4947.
Zou TB, Xia E, He TP, Huang MY, Jia Q and Li HW. Ultrasound-Assisted Extraction of Mangiferin from Mango (Mangifera indica L.) Leaves Using Response Surface Methodology. Molecules. 2014; 19: 1411-21. doi: 10.3390/molecules19021411.
Montañez GR, Ragazzo-Sánchez JA, Calderón-Santoyo M, Velázquez-de la Cruz G, Ramírez de León JA, Navarro-Ocaña A. Evaluation of extraction methods for preparative scale obtention of mangiferin and lupeol from mango peels (Mangifera indica L.). Food Chem. 2014; 159: 267-72. doi: 10.1016/j.foodchem.2014.03.009.
Jutiviboonsuk A, Sardsaengjun C. Mangiferinin Leaves of Three Thai Mango (Mangifera indica L.) Varieties. Isan J Pharm Sci. 2010; 6(3): 122-9. doi: 10.14456/ijps.2010.28.
Shindea SS and Chavanb AR. Isolation of Mangiferin from Different Varieties of Mangifera Indica Dried Leaves. Int J Sci Eng Res. 2014; 5(6): 928-34.
Semsri S, Khawon T, Sukasem J, Janwitayanuchit W, Nilsri N and Homvisasevongsa S. Effect of Eclipta prostrata, Chromolaena odorata, Centella asiatica (Linn.) Urban and Quercus infectoria Olivier extracts on in vitro hemostasis activities. Huachiew Chalermprakiet Sci Technol J. 2017; 3 (2): 42-53.
Alañón ME, Palomo I, Rodríguez L, Fuentes E, Román DA and Carretero AS. Antiplatelet Activity of Natural Bioactive Extracts from Mango (Mangifera Indica L.) and its By-Products. Antioxid. 2019; 8 (517): 1-11. doi: 10.3390/antiox8110517.
Ayodele OO, Anajobi FD, Osoniyi O. In vitro anticoagulant effect of Crassocephalum crepidioides leaf methanol extract and fractions on human blood. J Exp Pharmacol. 2019; 11: 99-107. doi: 10.2147/JEP.S218261.
Prasad S, Kashyap RS, Deopujari JY, Purohit HJ, Taori GM and Daginawala HF. Development of an in vitro model to study clot lysis activity of thrombolytic drugs. Thromb J. 2006; 4(14): 1-4. doi: 10.1186/1477-9560-4-14.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods. 1983; 65(1- 2): 55-63. doi: 10.1016/0022-1759(83)90303-4.
Berridge MV, Herst PM, Tan AS. Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol AnnU Rev. 2005; 11: 127-52. doi: 10.1016/S1387-2656(05)11004-7.
Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z, Falanga V. Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay. J Invest Dermatol. 2017; 137 (2): e11-e16. doi: 10.1016/j.jid.2016.11.020.
Jonkman JE, Cathcart JA, Xu F, Bartolini ME, Amon JE, Stevens KM, Colarusso P. An introduction to the wound healing assay using live-cell microscopy. Cell Adh Migr. 2014; 8 (5): 440-51. doi: 10.4161/cam.36224.
Cory G. Scratch-wound assay. Methods Mol Biol. 2011; 769: 25-30. doi: 10.1007/978-1-61779-207-6_2.
Correia-da-Silva M, Sousa E, Duarte B, Marques F, Carvalho F, Cunha-Ribeiro LM, Pinto M. Polysulfated Xanthones: Multipathway Development of a New Generation of Dual Anticoagulant/Antiplatelet Agents. J Med Chem. 2011; 54(15): 5373-80. doi: 10.1021/jm2006589.
Ain QU, Abid MUH, Hashim M, Ishaq S, Mansoor A, Perwasha P, Mizgan GE, Munawar SK, Khan IA. Anticoagulant and thrombolytic activities of leaf extract of Mangifera indica in smokers. Tob Regul. 2022; 8(1): 1189-201. doi: 10.18001/TRS.8.1.24.
Chi XV, Meng JJ, Lin CY, Su QS, Qin YY, Wei RH, Lan D and Huang C. Mangiferin Inhibits Human Lung Adenocarcinoma by Suppressing MiR-27b and MiR- 92a. Evid Based Complement Alternat Med. 2021; 2021: 1-10. doi.org/10.1155/2021/2822950.
Cheng XD, Gu JF, Yuan JR, Feng L and Jia XB. Suppression of A549 cell proliferation and metastasis by calycosin via inhibition of the PKCα/ERK1/2 pathway: An in vitro investigation. Mol Med Rep 2015; 12: 7992-8002. doi: 10.3892/mmr.2015.4449.
Chen Q, Men Y, Wang H, Chen R, Han X, and Liu J. Curcumin Inhibits Proliferation and Migration of A549 Lung Cancer Cells Through Activation of ERK1/2 Pathwayinduced Autophagy. Nat Prod Commun. 2019: 14(6): 1-7. doi: 10.1177/1934578X19848179.
Kim SY, Shin MS, Kim GJ, Kwon H, Lee MJ, Han AR, Nam JW, Jung CH, Kang KS and Choi H. Inhibition of A549 Lung Cancer Cell Migration and Invasion by Ent-Caprolactin C via the Suppression of Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition. Mar Drugs. 2021; 19: 465. doi: 10.3390/md19080465.