Prooxidant Effect of the Crude Ethanolic Leaf Extract of Ficus odorata Blanco Merr. in vitro: It’s Medical Significance

Alongside with antioxidant, pro-oxidant activity is also observed in phytochemical compounds. In the study, Ficus odorata, an endemic medicinal plant in the Philippines, was screened for the potential medical application of its pro-oxidant activity.

Phytochemical screening revealed the presence of terpenes, glycosides and phenolic acids. The crude extract was found to contain low gallic acid and quercetin equivalence. The TLC chromatogram of the crude extract showed that none of the 11 spots obtained has antioxidant activity nor correspond to gallic acid and quercetin standards. Experiments showed that the crude extract has stimulatory activity towards DPPH radicals, hydrogen peroxide, hydroxyl radicals, superoxide anions and nitric oxide. Moreover, the extract exhibited a low ferric reducing power.

The prooxidant activity was evident in the crude ethanolic leaf extract of F. odorata, which may provide a better understanding of the plant’s pharmacological importance in the prevention of diseases.





References:
[1] E.G. Guardado, E.M. Perez, M.J. Matos and E.U. Villares, "Antioxidant and Pro-oxidant Effects of Polyphenolic Compounds and Structure-Activity Relationship Evidence,” Nutrition, Well-Being and Health. Chapter 2, pp. 23-48, 2012.
[2] I.M.C.M. Rietjens, M.G. Boersma, L. de Haan, B. Spenkelink, H.M. Awad, N.H.P. Cnubben, J.J. van Zanden, H. van der Woude, G.M. Alink and J.H. Koeman, "The Pro-oxidant Chemistry of the Natural Antioxidants Vitamin C, Vitamin E, Carotenoids and Flavonoids”. Env Toxicol Pharmacol. Vol. 11 pp. 321-333, 2002.
[3] M. Carocho, and I.C.F.R. Ferreira, "A Review on Antioxidants, Prooxidants and Related Controversy: Natural and Synthetic Compounds, Screening and Analysis Methodologies and Future Perspectives,” Food Chem Toxicol vol. 51, pp. 15-25, 2013.
[4] J. Bouayed and T. Bohn, "Exogenous antioxidants—Double-edged swords in cellular redox state.Health beneficial effects at physiologic doses versus deleterious effects at high doses", Oxi Med Cell Long, vol. 3, no. 4, pp. 228-237, 2010.
[5] J.L. Schwartz, "The Dual Roles of Nutrients as Antioxidant and Prooxidants: Their Effects on Tumor Cell Growth,” J. Nutri, vol. 126, no. 4, pp. 1221S-1227S, 1996.
[6] J. Lambert and R. Elias, "The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention", Arch Biochem Biophys, vol. 501 No. 1, pp. 65-72, 2010.
[7] A.S. Azmi, S.H. Bhat, S. Hanif and S.M. Hadi, "Plant Polyphenols Mobilize Endogenous Copper in Human Peripheral Lymphocytes Leading to Oxidative DNA Breakage: A Putative Mechanism for Anticancer Properties,” FEBS Letters, vol. 580, no. 2, pp. 533-538, 2006.
[8] S.M. Hadi, S.H. Bhat, A.S. Azmi, S. Hanif, U. Shamim and M.F. Ullah, "Oxidative Breakage of Cellular DNA by Plant Polyphenols: A Putative Mechanism for Anticancer Properties,” Seminars Cancer Bio, vol. 17, no. 5, pp. 370-376, 2007.
[9] E.M. Odiatou, A.L. Skaltsounis and A.I. Constatinou, "Identification of the Factors Responsible for the In vitro Pro-oxidant and Cytotoxic Activities of the Olive Oil Polyphenols Oleuropein and Hydroxytyrosol,” Cancer Let, vol. 330, pp. 113-121, 2013.
[10] A.A. Herrera, J.B. Ramos and L.A. Ipulan, "Teratogenic activity of Ficus odorata (Blanco) Merr. And Baccaureate tandra (Baill.) Mull in mice embryos,” Phil Agri Sci, vol. 93, pp. 255-262, 2010.
[11] J.G.D. Alejandro, "Floristic Study and Flower Biology of Ficus species (Moraceae) Found in Mts. Palay-Palay-Mataas na Gulod National Park (Ternate, Cavite),” University of Santo Tomas: Manila, 1999.
[12] J.V. Pancho JV, "Vascular Flora of Mount Makiling and Vicinity (Luzon: Philippines). Kalikasan Press: Manila, 1983.
[13] L.A. Santiago and V.L.M. Valerio, "Assessment of Antioxidant Activities of Crude Ethanolic Leaf Extract of Ficus pseudopalma Blanco (Moraceae),” Intl. J. Pharma. Front. Res, vol. 3, no. 1, pp. 1-11, 2013.
[14] R. Manian, N. Anusuya, P. Siddhuraju and S. Manian, "The antioxidant activity and free radical scavenging potential of two different solvent extracts of Camellia sinensis (L.) O. Kuntz, Ficus bengalensis L. and Ficus racemosa L.,” Food Chem, vol. 107, pp. 1000-1007, 2008.
[15] J. Uttara and U. Mohini, "Evaluation of Antioxidant Activity of Aqueous Extract Bark of Ficus glomerata,” Res J Phar Tech, vol. 1, no. 4, pp. 537-538, 2008.
[16] P.R.P. Bueno, C.B.M. Buno, D.L.M. Santos and L.A. Santiago LA., "Assessment of the Antioxidant Activity of Ficus pseudopalma Blanco and its Cytotoxic Effect on Hepatocellular Carcinoma and Peripheral Blood Mononuclear Cells,” Curr Res Bio Pharma Sci, vol. 2, no. 2, pp. 14-21, 2013.
[17] B.Q. Guevarra, "A Guidebook to Plant Screening: Phytochemical and Biological”, Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila, 2005.
[18] M.B. Medina, "Determination of Total Phenolics in juices and superfruits by a novel chemical method,” J Func Food, vol. 3, pp. 79-87, 2011.
[19] M.A. Ebrahimzadeh, S.Y. Nabavi, S.F. Nabavi, F. Bahramian and A.R. Bekharadnia, "Antioxidant and free radical scavenging activity of H. officinalis I. var. angustifolius, v. odorata, b. hyrcana and c. specious,” Pakistan J. Pharma. Sci, vol. 23, p. 29-34, 2010.
[20] V. Kren and L. Martinkova, "Glycosides in Medicine: "The Role of Glycosidic Residues in Biological Activity,” Curr. Med. Chem, vol. 8, pp. 1303-1328, 2001.
[21] P.W. Tsai, K.H. De Castro-Cruz, C.C. Shu, C.T. Chiou and C.Y. Ragasa, "Chemical Constituents of F. odorata,” Pharma Chem J, vol. 46, no. 4, pp. 225-227, 2012.
[22] M.E. Leterlier, A. Molina-Berrios, J. Cortes-Troncoso, J. Jara-Sandoval, M. Holst, K. Palma, M. Montoya, D. Miranda and V. Gonzalez-Lira V, "DPPH and Oxygen Free Radicals as Pro-Oxidant of Biomolecules,” Toxicol In Vitro, vol. 22, pp. 279-286, 2008.
[23] R.M. Patel and N.J. Patel, "In vitro Antioxidant Activity of Coumarin Compounds by DPPH, Super Oxide and Nitric Oxide Free Radical Scavenging Methods,” J Adv Pharm Educ Res, vol. 1, pp. 52-68, 2011.
[24] A.S. Ahmed, E.E. Elgorashi, N. Moodley, L.J. McGaw, V. Naidoo and J.N. Eloff, "The Antimicrobial, Antioxidative, Anti-Inflammatory Activity and Cytotoxicity of Different Fractions of Four South African Bauhinia species Used Traditionally to Treat Diarrhoea,” J. Ethnopharmacol, http://dx.doi.org/10.1016/j.jep.2012.08.004, 2012.
[25] Y.X. Shi, Y.K. Xu, H.B. Hu, Z. Na and W.H. Wang, "Preliminary Assessment of Antioxidant Activity of Young Edible Leaves of Seven Ficus species in the Ethnic Diet in Xishuangbanna, Soutwest China,” Food Chem, Doi: 10.1016/j.foodchem.2011.03.113, 2011.
[26] P. Bellavite, "The Superoxide-forming Enzymatic System of Phagocytes,” Free Rad Bio Med, vol. 4, no. 4, pp. 225-261, 1988.
[27] M.K. Cathcart, "Regulation of Superoxide Anion Production by NADPH oxidase in Monocytes/Macrophages: Contributions to Atherosclerosis,” Arterios Thromb Vasc Bio, vol. 24, no. 1, pp. 23-28, 2004.
[28] J.R. Stone and S. Yang, "Hydrogen Peroxide: A Signaling Messenger,” Antioid Redox Signal, vol. 8, no. 3-4, pp: 243-270, 2006
[29] T. Djordjevic, A. Pogrebniak, R.S. Bel Aiba, S. Bonello, C. Wotzlaw, H. Acker, J. Hess and A. Gorlach, "The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells,” Free Rad Bio Med, vol. 38, pp. 616–630, 2005.
[30] H. Elouil, A.K. Cardozo, D.L. Eizirik , J.C. Henquin and J.C. Jonas JC, "High glucose and hydrogen peroxide increase c-Myc and haeme-oxygenase 1 mRNA levels in rat pancreatic islets without activating NFkB,” Diabetologia, vol. 48, pp. 496–505, 2005.
[31] Y.H. Hong, H.B. Peng, V. La Fata and J.K. Liao JK, "Hydrogen peroxide-mediated transcriptional induction of macrophage colony-stimulating factor by TGF-1,” J. Immuno, vol. 159, pp. 2418–2423 1997.
[32] A. Saccani, S. Saccani, S. Orlando, M. Sironi, S. Bernasconi, P. Ghezzi, A. Mantovani and A. Sica, "Redox regulation of chemokine receptor expression,” Pro Natl Acad Sci USA, vol. 97, pp. 2761–2766, 2000.
[33] D.A. Siwik, P.J. Pagano and W.S. Colucci, "Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts,” American J. Physio, vol. 280, pp.C53–C60, 2001.
[34] D. Bayer, J. Jansen and L.A. Beltz LA, "Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes,” Func Food Health Dis. 2 (4): 72-85, 2012.
[35] A. Gorman, A. McGowan and T.G. Cotter, "Role of Peroxide and Superoxide Anion during Tumor Cell Apoptosis,” FEBS Letter, vol. 404, no. 1, pp. 27-33, 1997.
[36] B. Halliwell, "Biochemistry of Oxidative Stress,” Biochem Soc Trans, vol. 35, pp. 1147-1150, 2007.
[37] K.M. Naseem, "The Role of Nitric Oxide in Cardiovascular Diseases,” Mol. Asp. Med. 26 (1-2): 33-65, 2005.
[38] M.K.O. Grant and E.E. El-Fakahany, "Therapeutic Interventions Targeting the Nitric Oxide System: Current and Potential Uses in Obstetrics, Bone Disease and Erectile Dysfunction,” Life Sciences, vol. 74, no. 14, pp. 1701-1721, 2004.
[39] C. Napoli, F. de Nigris, S. Williams-Ignarro, O. Pignalosa, V. Sica and L.J. Ignarro, "Nitric Oxide and Atherosclerosis: An Update,” Nitric Oxide, vol. 15 no. 4, pp. 265-279, 2006.
[40] P.O. Bonetti, L.O. Lerman and A. Lerman, "Endothelial Dysfunction: A Marker of Atherosclerotic Risk,” Arter Thromb Vasc Biol, vol. 23, no. 2, pp. 168-175, 2003.
[41] P.K. Kim, R. Zamora, P. Petrosko and T.R. Billiar, "The Regulatory Role of Nitric Oxide in Apoptosis,” Intl. Immunopharma, vol. 1, no. 8, pp. 1421-1441, 2001.
[42] L.J. Ignarro, P.A. Bush, G.M. Buga, K.S. Wood, J.M. Fukuto and J. Rajfer, "Nitric Oxide and Cyclic GMP Formation Upon Electrical Field Stimulation Cause Relaxation of Corpus Cavernosum Smooth Muscle,” Biochem Biophysic Res Com, vol. 170, no. 2, pp. 843-850, 1990.
[43] C. Marin-Cordero, A.J. Leon-Gonzales, J.M. Calderon-Monero, E. Burgos-Moron and M. M. Lopez-Lazaro, "Pro-oxidant Natural Products as Anticancer Agents,” Cur Drug Tar, vol. 13, no. 8, pp. 1006-1028, 2012.
[44] C. Puglia and S. Powell, "Inhibition of cellular antioxidants: a possible mechanism of toxic cell injury. ", Environ. Health Perspect. , vol. 57, pp. 307-311, 1984.
[45] O. Aruoma, "Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods", Mut Res, vol. 523-524, pp. 9-20, 2003.
[46] L. James, et al., "Acetaminophen-induced hepatotoxicity", Drug Metab.Dispos., vol. 31, no. 12, pp. 1499-1506, 2003.
[47] S. Astley and D. Lindsay, "European Research on the Functional Effects of Dietary Antioxidants", Mol Asp Med, vol. 23 pp. 1-3, 2002.