2441 INTERLEUKIN-1B AND CYCLOOXYGENASE-2 PROINFLAMMATION ANALYSIS AND IN SILICO DOCKING NUCLEAR FACTOR KAPPA B ON ENDOMETRIOSIS CELL CULTURE GIVEN HEPTYL GALLATE AND OCTYL GALLATE TREATMENT

The aim of this study is to analyze the effect of octyl gallate and heptyl gallate toward the regulation of interleukin-1β and cyclooxygenase (COX)-2 proinflammatory factor on endometriosis cell culture and analyze its activity toward nuclear factor kappa B (NFkB) target protein through in silico docking technique.

In vitro study was performed on endometriosis cells cultured treated with two dosages each of heptyl and octyl gallate (51.2 μg/mL and 102.4 μg/mL) for 48 h, then followed by 10 ng/mL lipopolysaccharides (LPS) induction for 24 h. The positive control group was treated by LPS induced and the negative control was treated without LPS. Inflammation regulation was evaluated with enzyme-linked immunosorbent assay technique and in silico docking analyzed using bioinformatics technique.

Molecular docking analysis with gallic acid and their derivatives showed that more stable affinity and stronger binding found on octyl gallate than heptyl gallate and gallic acid at the active site of NFkB.

Based on this study results, octyl gallate and heptyl gallate were proven to be able to reduce COX-2 proinflammatory factor through NFkB pathway as an inflammatory regulator; thus, it has the potential to be developed as a therapy for endometriosis. Downloads

Hidetaka HR. Pathological Aspect and Pathogenesis of Endometriosis. In: Harada T, editor. Endometriosis Pathogenesis and Treatment. Japan: Springer; 2014. p. 9-18. Johnson NP, Hummelshoj L. World endometriosis society montpellier C. Consensus on current management of endometriosis. Hum Reprod 2013;28:1552-68. Halis G, Arici A. Endometriosis and inflammation in infertility. Ann N Y Acad Sci 2004;1034:300-15. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril 2012;98:511-9. Wu MH, Hsiao KY, Tsai SJ. Endometriosis and possible inflammation markers. Gynecol Minim Invasive Ther 2015;4:61-7. McKinnon BD, Bertschi D, Bersinger NA, Mueller MD. Inflammation and nerve fiber interaction in endometriotic pain. Trends Endocrinol Metab 2015;26:1-0. Rinata E, Noorhamdani S. Pemberian genistein pada kultur sel endometriosis dalam menurunkan kadar interleukin-1β. Obstet Ginekol 2014;22:39-45. Ahmad SF, Rakhila H, Akoum A. Macrophages in pathophysiology of endometriosis. In: Harada T, editor. Endometriosis Pathogenesis and Treatment. Canada: Springer; 2014. p. 61-85. Huang F, Cao J, Liu Q, Zou Y, Li H, Yin T, et al. MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1β induced in human endometriosis stromal cells in vitro. Int J Clin Exp Pathol 2013;6:2129-36. Tao X, Xie Y, Wang L, Gu W, Yu X, Zhou X, et al. The expression of cox-2, NF-κB, and VEGF in ectopic endometrial tissues within fallopian tubes suggests different etiologies. Int J Gynecol Pathol 2014;33:411-7. Wu Y, Guo SW. Suppression of IL-1beta-induced COX-2 expression by trichostatin A (TSA) in human endometrial stromal cells. Eur J Obstet Gynecol Reprod Biol 2007;135:88-93. Choubey S, Varughese LR, Kumar V, Beniwal V. Medicinal importance of gallic acid and its ester derivatives: A patent review. Pharm Pat Anal 2015;4:305-15. Locatelli C, Filippin-Monteiro FB, Creczynski-Pasa TB. Alkyl esters of gallic acid as anticancer agents: A review. Eur J Med Chem 2013;60:233-9. Feng Q, Kumagai T, Nakamura Y, Uchida K, Osawa T. Correlation of antimutagenic activity and suppression of CYP1A with the lipophilicity of alkyl gallates and other phenolic compounds. Mutat Res 2003;537:101-8. Tammela P, Laitinen L, Galkin A, Wennberg T, Heczko R, Vuorela H, et al. Permeability characteristics and membrane affinity of flavonoids and alkyl gallates in caco-2 cells and in phospholipid vesicles. Arch Biochem Biophys 2004;425:193-9. Bustami PS, Muharam R, Wibowo H. Effects of gallic acid and its derivates on inflammatory regulation of endometriotic primary cultures study on NFkB mRNA expression and IL6 secretion. Biomed Pharm J 2018;11:3. Syahputra AL, Sumaryada T. Simulasi docking kurkumin enol, bisdementoksikurkumin dan analognya sebagai inhibitor enzim12- lipoksigenase. J Biofis 2014;10:55-67. Ranganatha SS, Govindappa M, Ramachandra YL. In silico studies of NF-κB protein as anti-cancer and anti-inflammatory target. J Comp Method Mol Design 2013;3:26-33. Ulfa DM, Arsianti A, Radji M. In silico docking studies of gallic acid structural analogues as Bcl-Xl inhibitor in cancer. Asian J Pharm Clin Res 2017;10:119. Faried A, Kurnia D, Faried LS, Usman N, Miyazaki T, Kato H, et al. Anticancer effects of gallic acid isolated from indonesian herbal medicine, phaleria macrocarpa (Scheff.) boerl, on human cancer cell lines. Int J Oncol 2007;30:605-13. Arsianti AA, Astuty H, Fadilah F, Bahtiar A, Tanimoto H, Kakiuchi K. Design and screening of gallic acid derivatives as inhibitors of malarial dihydrofolate reductase (Dhfr) by in silico docking. Asian J Pharm Clin Res 2017;10:330. Wulandari OM, Tjandrawinata RR. Bioctive fraction DLBS2411 from Cinnamomum burmannii, (Nees and T.Nees) Blume as colon and gastroprotector by stimulating MUC5AC and cyclooxygenase-2 gene expression. Int J Pharm Pharm Sci 2016;8:202-7. Budi PG, Sumapraja K, Natadisastra M, Harzief HS, Pratama G, Hestiantoro A. Penggunaan DLBS1442 untuk terapi medikamentosa terkini pada penderita endometriosis. Medicinus 2013;26:4-7. Bustami SS, Sopiah PP, Zoya MA, Ade A, Natadisastra RM. Cell viability inhibition effect of gallic acid and its synthetic derivative forms on primary cultured endometriosis cells. Adv Sci Lett 2017;23:6681-3. Bustami HD, Adyasa ZM, Nareswari SS, Sopiah P, Arsianti A, Natadisastra RM. The apoptotic effect of gallic acid and its derivatives on primary cultured endometriosis cells. Adv Sci Lett 2017;23:6695-8. Published How to Cite Issue Section The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.