Ficus elastica Leaf Extract Effect Toward IL-10 and TNF-? as a Preeclampsia Model on Hypoxia-induced EA.hy926
DOI:
https://doi.org/10.5614/j.math.fund.sci.2021.53.3.10Keywords:
EA.hy926, Ficus elastica, hypoxia, IL-10, preeclampsia, TNF-?Abstract
Preeclampsia is a pregnancy complication characterized by proteinuria, hypertension, hypoxia as well an increased systemic inflammatory response. It affects 5 to 10% of all births and is a leading factor in fetal and maternal morbidity and death. Ficus elastica L. leaves are known to have natural compounds with anti-inflammatory and antioxidant properties. This research assessed the potential of F. elastica leaf extract (FEE) as anti-inflammatory agent in a hypoxic-induced human endothelial cell line (EA.hy926) as preeclampsia model. F. elastica leaves were extracted using 70% ethanol. Cytotoxic assay of the FEE in different concentrations (3.13 to 100 g/ml) against EA.hy926 was done using MTS assay. The FEE?s anti-inflammatory activity was measured with ELISA for the TNF-? and IL-10 parameters. The FEE did not cause cytotoxicity to the EA.hy926 cells, with viability above 80% at the highest concentration. The FEE could decrease the pro-inflammatory TNF-? level and increase the IL-10 level as anti-inflammatory markers in the preeclampsia model at significance level p<0.05. This study suggests that FEE is a safe alternative herbal medicine for preeclampsia treatment.
References
Portelli, M. & Baron, B., Clinical Presentation of Preeclampsia and the Diagnostic Value of Proteins and Their Methylation Products as Biomarkers in Pregnant Women with Preeclampsia and Their Newborns, J. Pregnancy., 2018(1), pp. 1-23, 2018.
Peres, G., Mariana, M. & Cairr, E., Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied in Portugal, J. Cardiovasc. Dev. Dis., 5(1), pp. 1-13, 2018.
Cheraghi, Z., Esfahani, B.O., Mohammadian, Z. & Nooreldinc, R.S., Prevalence of Preeclampsia and Eclampsia in Iran, Arch. Iran. Med., 19(1), pp. 64-71, 2016.
Cornelius, D.C., Preeclampsia: From Inflammation to Immunoregulation, Clin. Med. Insights Blood Disord., 11(2018), pp.1-6, 2018.
Nair, M.P., Mahajan, S., Reynolds, J.L., Aalinkeel, R., Nair, H., Schwartz, S.A. et al., The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral Blood Mononuclear Cells via Modulation of the NF-System, Clin. Vaccine Immunol., 13(3), pp. 319-328, 2006.
Hung, T-H., Charnock-Jones, D.S., Skepper, J.N. & Burton, G.J., Secretion of Tumor Necrosis Factor-Alpha from Human Placental Tissues Induced by Hypoxia-Reoxygenation Causes Endothelial Cell Activation In Vitro: A Potential Mediator of The Inflammatory Response in Preeclampsia, Am. J. Pathol., 164(3), pp. 1049-1061, 2004.
Iyer, N.V., Kotch, L.E., Agani, F., Leung, S.W., Laughner, E. & Wenger, R.H., et al., Cellular and Developmental Control of O2 Homeostasis by Hypoxia-Inducible Factor 1-Alpha, Genes. Dev., 12(2), pp. 149-162, 1998.
Eltzschig, H.K. & Carmeliet, P., Hypoxia and Inflammation, N. Engl. J. Med., 364(7), pp. 656-665, 2011.
Sammour, M.B., El-Kabarity, H., Fawzy, M.M. & Schindler, A.E., Prevention and Treatment of Pre-Eclampsia and Eclampsia, J. Steroid Biochem. Mol. Biol., 97(5), pp. 439-440, 2011.
Friedman, J.M., ACE Inhibitors and Congenital Anomalies, N. Engl. J. Med., 354(23), pp. 24982500, 2006.
Ginting, C., Lister, I.N.E., Girsang, E., Putri, Y., Mutia, M., Purba, R. et al., In Silico Anti-Preeclampsia Potential of Phytochemical Found in Ficus elastica, Pharmacog. Res., 11(3), pp. 279-282, 2019.
Comalada, M., Camuesco, D., Sierra, S., Ballester, I., Xaus, J., Gvez, J. et al. In Vivo Quercitrin Anti-Inflammatory Effect Involves Release of Quercetin, which Inhibits Inflammation through Down-Regulation of the NF-?B Pathway, Eur. J. Immunol., 35(2), pp. 584-592, 2005.
di Gesso, J.L., Kerr, J.S., Zhang, Q., Raheem, S., Yalamanchili, S.K., O?Hagan, D., et al., Flavonoid Metabolites Reduce Tumor Necrosis Factor-? Secretion to a Greater Extent than their Precursor Compounds in Human THP-1 Monocytes, Mol. Nutr. Food Res., 59(6), pp. 1143-1154, 2015.
Ginting, C.N., Lister, I.N.E., Girsang, E., Riastawati, D., Kusuma, H.S.W. & Widowati, W. Antioxidant Activities of Ficus elastica Leaves Ethanol Extract and Its Compounds. Mol. Cell. Biomed. Sci., 4(1), pp. 27-33, 2020.
Widowati, W., Wijaya, L., Bachtiar, I., Gunanegara, R.F., Sugeng, S.U., Irawan, Y.A. et al., Effect of Oxygen Tension on Proliferation and Characteristics of Wharton?s Jelly-derived Mesenchymal Stem Cells, Biomarkers Genomic Med., 6(1), pp. 43-48, 2014.
Widowati, W., Wijaya, L., Murti, H., Widyastuti, H., Agustina, D., Laksmitawati, D.R., et al., Conditioned Medium from Normoxia (WJMSCs-norCM) and Hypoxia-Treated WJMSCs (WJMSCs-hypoCM) in Inhibiting Cancer Cell Proliferation, Biomarkers Genomic Med., 7(1), pp. 8-17, 2015.
Ginting, C.N., Lister, I.N.E., Girsang, E., Mutia, M.S., Lubis, Y.E.P., Amalia, A., et al., Anti-inflammatory Activity of Quercitrin on Hypoxia-induced EA. hy926. J. Phys. Conf. Ser., 1374(1), pp. 1-7, 2019.
Luo, R., Wang, Y., Xu, P., Cao, G., Zhao, Y., Shao, X. et al., Hypoxia-Inducible miR-210 Contributes to Preeclampsia Via Targeting Thrombospondin Type I Domain Containing 7A. Sci. Rep., 6(1), pp. 1-11, 2016.
Aouache, R., Biquard, L., Vaiman, D & Miralles, F., Oxidative Stress in Preeclampsia and Placental Diseases, Int. J. Mol. Sci., 19(5), pp. 1-29, 2018.
Kruger, NJ., The Bradford Method for Protein Quantitation, in The Protein Protocols Handbook, Humana Press, pp. 17-24, 2009.
Widowati, W., Murti, H., Jasaputra, D.K., Sumitro, S.B., Widodo, M.A., Fauziah, N. et al., Selective Cytotoxic Potential of IFN-? and TNF-? on Breast Cancer Cell Lines (T47D and MCF7), Asian. J. Cell Biol., 11(1), pp. 1-12, 2016.
Sandhiutami, N.M.D., Moordiani, M., Laksmitawati, D.R., Fauziah, N., Maesaroh, M. & Widowati, W., In Vitro Assesment of Anti-Inflammatory Activities of Coumarin and Indonesian Cassia Extract in RAW264.7 Murine Macrophage Cell Line, Iran. J. Basic Med. Sci., 20(1), pp. 99-106, 2017.
Banimuslem, T.A.J., Al-Yassari, A.K.S. & Marza, A.D., Modulation of Lipopolysaccharide-Induced Cytokines Response in Mice by Graviola Leaf Powder, Plant Arch., 19(1), pp. 791-797, 2019.
Mihu, D., Razvan, C., Malutan, A. & Mihaela, C., Evaluation of Maternal Systemic Inflammatory Response in Preeclampsia, Taiwan J. Obstet. Gynecol., 54(2), pp. 160-166, 2015.
Zhou, J., Xiao, D., Hu, Y., Wang, Z., Paradis, A., Mata-Greenwood, E. et al., Gestational Hypoxia Induces Preeclampsia-like Symptoms via Heightened Endothelin-1 Signaling in Pregnant Rats, Hypertension, 62(3), pp. 599-607, 2013.
Bartels, K., Grenz, A. & Eltzschig, H.K., Hypoxia and Inflammation are Two Sides of The Same Coin, Proc. Natl. Acad. Sci., 110(46), pp. 18351-18352, 2013.
Vitoratos, N., Economou, E., Iavazzo, C., Panoulis, K. & Creatsas, G., Maternal Serum Levels of TNF-Alpha and IL-6 Long after Delivery in Preeclamptic and Normotensive Pregnant Women, Mediators. Inflamm., 2010(2010), pp. 1-6, 2010.
Heo, Y-J., Joo, Y-B., Oh, H-J., Park, M-K., Heo, Y-M., Cho, M-L. et al., IL-10 Suppresses Th17 Cells and Promotes Regulatory T Cells in the CD4+ T Cell Population of Rheumatoid Arthritis Patients, Immunol. Lett., 127(2), pp. 150-156, 2010.
Harmon, A.C., Cornelius, D.C., Amaral, L.M., Faulkner, J.L., Cunningham, M.W., Wallace, K. et al., The Role of Inflammation in the Pathology of Preeclampsia, Clin. Sci., 130(6), pp. 409-419, 2016.
Mittal, M., Siddiqui, M.R., Tran, K., Reddy, S.P. & Malik, A.B., Reactive Oxygen Species in Inflammation and Tissue Injury, Antioxid. Redox Signaling 20(7), pp. 1126-1167, 2014.
Rajan, T.S., Giacoppo, S., Iori, R., De Nicola, G.R., Grassi, G., Pollastro, F. et al., Anti-Inflammatory and Antioxidant Effects of a Combination of Cannabidiol and Moringin in LPS-Stimulated Macrophages, Fitoter. 112(2016), pp. 104-115, 2016.
Qutub, A.A. & Popel, A.S., Reactive Oxygen Species Regulate Hypoxia-Inducible Factor 1-Alpha Differentially in Cancer and Ischemia, Mol. Cell Biol., 28(16), pp. 5106-5119, 2008.
Azimi, I., Petersen, R.M., Thompson, E.W., Roberts-Thomson, S.J. & Monteith, G.R., Hypoxia-Induced Reactive Oxygen Species Mediate N-Cadherin and SERPINE1 Expression, EGFR Signalling and Motility in MDA-MB-468 Breast Cancer Cells, Sci. Rep., 7(1), pp.1-11, 2017.
Arulselvan, P., Fard, M.T., Tan, W.S., Gothai, S., Fakurazi, S., Norhaizan, M.E. et al., Role of Antioxidants and Natural Products in Inflammation, Oxid. Med. Cell. 20 Longevity, 2016, pp. 1-15, 2016.
Kiem, P.V., Minh, C.V., Nhiem, N.X., Tai, B.H., Quang, T.H., Anh, H.L.T. et al., Chemical Constituents of the Ficus elastica Leaves and Their Antioxidant Activities, Bull. Korean Chem. Soc., 33(10), pp. 3461-3464, 2012.
Ginting, C.N., Lister, I.N.E., Girsang, E., Artie, D.S., Aviani, J.K., Widowati, W. Apoptotic, MDA, and FGF2 Level of Quercitrin Treatment on Hypoxic-Induced EA. hy926 Cell Line, J. Rep. Pharm. Sci., 10(1), pp. 22-28, 2021.
