Antioxidant and antiproliferative properties of Moringa oleifera Lam. leaf aqueous extract
DOI:
https://doi.org/10.14719/pst.2020.7.4.936Keywords:
Moringa oleifera, Antioxidant activity, LCMS QTOF, Emodin-8-glucoside, Antiproliferative activity , Molecular dockingAbstract
Moringa oleifera Lam. is a highly valued medicinal plant in India, especially Kerala. In the present study, antioxidant activity of aqueous extract of leaves of M. oleifera was determined both in-vitro and in-vivo. Male Wistar rats of 3 age groups- 6, 12, and 18 months old were used for in-vivo analysis. In vitro anti-proliferative effect of the extract was carried out in Dalton’s Lymphoma Ascites (DLA) Cells. LCMS-QTOF analysis of the extract was also done to determine the bioactive components present in the extract. Antioxidant activity of M. oleifera leaf showed an IC 50 value of 10.47 ?g/ml and whereas for standard drug, ascorbic acid, it was 19.52 ?g/ml. In-vivo analysis of lipid peroxidation showed a significant reduction of lipid peroxidation in the brains of 12 and 18-months old treated groups. Up to 75% mortality of DLA cancerous cells was observed in-vitro in different concentrations of M. oleifera leaf water extract in a dose-dependent manner, demonstrating its anti-proliferative property. LCMS-QTOF analysis revealed the presence of emodin-8-glucoside in the extract. Molecular docking analysis (Auto Dock Vina) of emodin-8-glucoside with six cancer related proteins showed highest binding affinity with AKT-1 with a binding score of -10.4 kcal/mol, also showed good affinity with NF-kB (p65), Stat-3, Bcl-2, Bcl-xl and c-FLIP. This study helps to choose healthy diet practices to overcome free radical onslaught and cancerous cell proliferation especially in the later stages of life. This can also pave way for the emergence of diet based therapeutic cure for cancer.
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References
Rao AV, Uma Devi P, Kamath R. In-vivo radioprotective effect of Moringa oleifera leaves. Indian J Exp Biol. 2001;39(9):858-63.
Guevara AP, Vargas C, Sakurai H, Fujiwara Y, Hashimoto K, Maoka T, et al. An antitumor promoter from Moringa oleifera Lam. Mutat Res - Genet Toxicol Environ Mutagen. 1999; 440(2):181-8. https://doi.org/10.1016/s1383-5718(99)00025-x
Murakami A, Kitazono Y, Jiwajinda S, Koshimizu K, Ohigashi H. Niaziminin. A thiocarbamate from the leaves of Moringa oleifera holds a strict structural requirement for inhibition of tumor-promoter-induced epstein-barr virus activation. Planta Med. 1998;64(4):319-23. https://doi.org/10.1055/s-2006-957442
Faizi S, Siddiqui BS, Saleem R, Aftab K, Shaheen F, Gilani AUH. Hypotensive constituents from the pods of Moringa oleifera. Planta Med. 1998;64(3):225-28.
Patel P, Patel N, Patel D, Desai S, Meshram D. Phytochemical analysis and antifungal activity of Moringa oleifera. Int J Pharm Pharm Sci. 2014;6(5):144-47.
Cáceres A, Saravia A, Rizzo S, Zabala L, De Leon E, Nave F. Pharmacologie properties of Moringa oleifera. 2: Screening for antispasmodic, antiinflammatory and diuretic activity. J Ethnopharmacol. 1992;36(3):233-37. https://doi.org/10.1016/0378-8741(92)90049-w
Leone A, Fiorillo G, Criscuoli F, Ravasenghi S, Santagostini L, Fico G, et al. Nutritional characterization and phenolic profiling of Moringa oleifera leaves grown in chad, sahrawi refugee camps and Haiti. Int J Mol Sci. 2015;16(8):18923-37. https://doi.org/10.3390/ijms160818923
Nile SH, Keum YS, Nile AS, Jalde SS, Patel R V. Antioxidant, anti-inflammatory and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives. J Biochem Mol Toxicol. 2018;32(1). https://doi.org/10.1002/jbt.22002
Sinha M, Das DK, Datta S, Ghosh S, Dey S. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract. Indian J Exp Biol. 2012;50(3):209-15.
Han YM, Lee SK, Jeong DG, Ryu SE, Han DC, Kim DK, et al. Emodin inhibits migration and invasion of DLD-1(PRL-3) cells via inhibition of PRL-3 phosphatase activity. Bioorg Med Chem Lett. 2012;22:323–26. https://doi.org/10.1016/j.bmcl.2011.11.008
Manu KA, Shanmugam MK, Ong TH, Subramaniam A, Siveen KS, Perumal E, et al., Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS One. 2013;8(3):e57015.
Ok S, Kim SM, Kim C, Nam D, Shim BS, Kim SH, et al. Emodin inhibits invasion and migration of prostate and lung cancer cells by downregulating the expression of chemokine receptor CXCR4. Immunopharmacol Immunotoxicol. 2012;34(5):768–78. https://doi.org/10.3109/08923973.2012.654494
Harborne JB. Phytochemical Methods: A guide to modern techniques of plant analysis. Chapman and Hall Ltd., London. 1973.
Trease GE, Evans WC. Pharmacognosy Brailliar Tiridel Can, 13th ed. Macmillian Publishers. 1989.
Sofowara A. Medicinal Plants and Traditional Medicine in Africa. Spectrum Books Limited, Ibadan, Nigeria, 1993. pp. 289.
Kasote DM, Jayaprakasha GK, Patil BS. Leaf Disc Assays for rapid measurement of antioxidant activity. Sci Rep. 2019;9:1884. https://doi.org/10.1038/s41598-018-38036-x
Dolly Jaiswal, Prashant Kumar Rai, Shikha Mehta, Sanjukta Chatterji, Surekha Shukla, Devendra Kumar Rai et al. Role of Moringa oleifera in regulation of diabetes-induced oxidative stress. Asian Pacific Journal of Tropical Medicine. 2013;426-32. https://doi.org/10.1016/S1995-7645(13)60068-1
Awodelea O, Oreagbaa IA, Odomaa S, Teixeira da Silva JA, Osunkalu VO. Toxicological evaluation of the aqueous leaf extract of Moringa oleifera Lam. (Moringaceae). J Ethnopharmacol. 2012;139(2):330-36. https://doi.org/10.1016/j.jep.2011.10.008
Fraga CG, Leibovitz BE, Tappel AL. Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes. Free Radic Biol Med. 1988;4(3):155-61. https://doi.org/10.1016/0891-5849(88)90023-8
Talwar GP, Gupta SK. A Handbook of Practical and Clinical Immunology. CBS Publishers & Distributors. 1992. pp. 436.
Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem. 2009;31(2):455–61. https://doi.org/10.1002/jcc.21334
Charoensin S. Antioxidant and Anticancer Activities of Moringa oleifera Leaves. Journal of Medicinal Plants Research. 2014;8(7):318-25.
Mahdi JH, Yousif EM, Khan NA, Mahmud R, Murugaiyah V, Asmawi MZ. Optimizing extraction conditions of Moringa oleifera Lam. leaf for percent yield, total phenolics content, total flavonoids content and total radical scavenging activity. International Journal of Advanced Research. 2016;4(11):682-95. https://doi.org/10.21474/IJAR01/2133
Potterat O. Antioxidants and free radical scavengers of natural origin. Current Organic Chemistry. 1997;1(4):415-40.
Lin M, Zhang J, Chen X. Bioactive flavonoids in Moringa oleifera and their health-promoting properties. Journal of Functional Foods. 2018;47:469-79.
Sreelatha S, Padma PR. Antioxidant activity and total phenolic content of Moringa oleifera leaves in two stages of maturity. Plant Foods Hum Nutr. 2009;64(4):303-11. https://doi.org/10.1007/s11130-009-0141-0
Knekt P, Kumpulainen J, Järvinen R, Rissanen H, Heliövaara M, Reunanen A, et al. Flavonoid intake and risk of chronic diseases. Am J Clin Nutr. 2002;76(3):560-68. https://doi.org/10.1093/ajcn/76.3.560
Nile SH, Keum YS, Nile AS, Jalde SS, Patel R V. Antioxidant, anti-inflammatory and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives. J Biochem Mol Toxicol. 2018;32(1). https://doi.org/10.1002/jbt.22002
Sinha M, Das DK, Datta S, Ghosh S, Dey S. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract. Indian J Exp Biol. 2012;50(3):209-15.
Terao J, Piskula MK. Flavonoids and membrane lipid peroxidation inhibition. Nutrition. 1999;(10):790-91. https://doi.org/10.1016/s0899-9007(99)00159-8
Kirisattayakul W, Wattanathorn J, Tong-Un T, Muchimapura S, Wannanon P, Jittiwat J. Cerebroprotective effect of Moringa oleifera against focal ischemic stroke induced by middle cerebral artery occlusion. Oxid Med Cell Longev. 2013; 2013:951415. https://doi.org/10.1155/2013/951415
Idoga ES, Ambali SF, Ayo JO, Mohammed A. Assessment of antioxidant and neuroprotective activities of methanol extract of Moringa oleifera Lam. leaves in subchronic chlorpyrifos-intoxicated rats. Comp Clin Path. 2018;917–25. https://doi.org/10.1007/s00580-018-2682-9
Tiloke C, Phulukdaree A, Chuturgoon AA. The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on human esophageal cancer cells. J Med Food. 2016;19(4):398-403. https://doi.org/10.1089/jmf.2015.0113
Jafarain A, Asghari G, Ghassami E. Evaluation of cytotoxicity of Moringa oleifera Lam. callus and leaf extracts on Hela cells. Adv Biomed Res. 2014;3:194. https://doi.org/10.4103/2277-9175.140668
Tiloke C, Phulukdaree A, Chuturgoon AA. The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on cancerous human alveolar epithelial cells. BMC Complement Altern Med. 2013;16;13:226. https://doi.org/10.1186/1472-6882-13-226
Varalakshmi K, Nair S. Anticancer, cytotoxic potential of Moringa oleifera extracts on HeLa cell line. J Nat Pharm. 2011;2(3):138. https://doi.org/10.4103/2229-5119.86260
Özenver N, Saeed M, Demirezer L ömur, Efferth T. Aloe-emodin as drug candidate for cancer therapy. Oncotarget. 2018;9(25):17770-96. https://doi.org/10.18632/oncotarget.24880
Jelassi B, Anchelin M, Chamouton J, Cayuela ML, Clarysse L, Li J, et al. Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors. Carcinogenesis. 2013;34(7):1487-96. https://doi.org/10.1093/carcin/bgt099
Pérez-Tenorio G, Stål O, Arnesson LG, Malmström A, Nordenskjöld B, Nordenskjöld K, et al. Activation of Akt/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer. 2002;86(4):540–45. https://doi.org/10.1038/sj.bjc.6600126
Gonzalez E, McGraw TE. The Akt kinases: Isoform specificity in metabolism and cancer. Cell Cycle. 2009;15:8(16):2502–08. https://doi.org/10.4161/cc.8.16.9335
Chen WS, Xu PZ, Gottlob K, Chen ML, Sokol K, Shiyanova T, et al. Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 gene. Genes Dev. 2001;15(17):2203–08. https://doi.org/10.1101/gad.913901
Arcaro A, Guerreiro A. The phosphoinositide 3-kinase pathway in human cancer: Genetic alterations and therapeutic implications. Curr Genomics. 2007;8(5):271–306. https://doi.org/10.2174/138920207782446160
Moll UM, Petrenko O. The MDM2-p53 Interaction. Molecular Cancer Research. 2003. l. 1, 1001–08.
Mayo LD, Donner DB. The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network. Trends in Biochemical Sciences. 2002;27(9):462-67. https://doi.org/10.1016/s0968-0004(02)02166-7
Song W, Mazzieri R, Yang T, Gobe GC. Translational significance for tumor metastasis of tumor-associated macrophages and epithelial-mesenchymal transition. Frontiers in Immunology. 2017;8:1106. https://doi.org/10.3389/fimmu.2017.01106
Zhong L, Chen XF, Wang T, Wang Z, Liao C, Wang Z, et al. Soluble TREM2 induces inflammatory responses and enhances microglial survival. J Exp Med. 2017;6;214(3):597-607. https://doi.org/10.1084/jem.20160844
Tosello V, Bordin F, Yu J, Agnusdei V, Indraccolo S, Basso G, et al. Calcineurin and GSK-3 inhibition sensitizes T-cell acute lymphoblastic leukemia cells to apoptosis through X-linked inhibitor of apoptosis protein degradation. Leukemia. 2016; 30(4):812-22. https://doi.org/10.1038/leu.2015.335
Kwon HJ, Choi GE, Ryu S, Kwon SJ, Kim SC, Booth C, et al. Stepwise phosphorylation of p65 promotes NF-ΰ B activation and NK cell responses during target cell recognition. Nat Commun. 2016;7:11686. https://doi.org/10.1038/ncomms11686
Nelson EA, Walker SR, Kepich A, Gashin LB, Hideshima T, Ikeda H, et al. Nifuroxazide inhibits survival of multiple myeloma cells by directly inhibiting STAT3. Blood. 2008; 15;112(13):5095-102. https://doi.org/10.1182/blood-2007-12-129718
Certo M, Moore VDG, Nishino M, Wei G, Korsmeyer S, Armstrong SA, et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 2006;9(5):351-65. https://doi.org/10.1016/j.ccr.2006.03.027
Cheng EHY, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, et al. BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell. 2001;8(3):705-11. https://doi.org/10.1016/s1097-2765(01)00320-3
Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis serving as prototype cancer therapeutics. Cancer Cell. 2002;2(3):183-92. https://doi.org/10.1016/s1535-6108(02)00127-7
Lessene G, Czabotar PE, Colman PM. BCL-2 family antagonists for cancer therapy. Nature Reviews Drug Discovery. 2008. 7(12):989-1000. https://doi.org/10.1038/nrd2658
Delbridge ARD, Grabow S, Strasser A, Vaux DL. Thirty years of BCL-2: Translating cell death discoveries into novel cancer therapies. Nature Reviews Cancer. 2016;16(2):99-109. https://doi.org/10.1038/nrc.2015.17
Petros AM, Dinges J, Augeri DJ, Baumeister SA, Betebenner DA, Bures MG, et al. Discovery of a potent inhibitor of the antiapoptotic protein Bcl-X L from NMR and parallel synthesis. J Med Chem. 2006;49(2):656–63. https://doi.org/10.1021/jm0507532
Safa AR. c-FLIP, a master anti-apoptotic regulator. Experimental Oncology. 2012;34(3):176–84.
Shirley S, Micheau O. Targeting c-FLIP in cancer. Cancer Letters. 2013;28;332(2):141-50. https://doi.org/10.1016/j.canlet.2010.10.009
Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-?B in cell growth regulation. American Journal of Pathology. 2001;159(2):387–97. https://doi.org/10.1016/s0002-9440(10)61708-7
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