The Differences of Malondialdehyde Serum Level, Expression of Tumor Necrosis Factor Alpha and Vascular Endothelial Growth Factor, and the Area of Endometriotic Implants in Administration of Kebar Grass Extract (Biophytum petersianum) and Green Tea Extract (Camelia sinensis) to Mice

Yuli Trisetiyono(1*), Noor Pramono(2), Syarief Thaufik Hidayat(3), Widjiati Widjiati(4)

(1) Reproductive Endocrinology and Infertility Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Diponegoro University, Indonesia
(2) Reproductive Endocrinology and Infertility Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Diponegoro University, Indonesia
(3) Reproductive Endocrinology and Infertility Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Diponegoro University, Indonesia
(4) Department of Embryology, Faculty of Veterinary Medicine, Airlangga University, Indonesia
(*) Corresponding Author


The pathological pathway of endometriosis remains unclear and involves complex etiologies. Increased oxidative stress is understood to be related to this disease. Oxidative stress produces reactive oxygen species, causes inflammation that is characterized by recruiting lymphocytes and phagocyte activation, produces cytokines that induce oxidation enzyme, and supports epithelium growth. Oxidative stress conjointly will increase angiogenesis and promotes the proliferation of endometriosis tissue within the peritoneal cavity. Kebar grass and green tea contain high antioxidants, are expected to extend antioxidant defense leading to reduced oxidative stress, inflammation, angiogenesis, and reduced endometriosis tissue implants. The objective is to analyze the consequences of Kebar grass and green tea extract to MDA serum level, TNF-α, and VEGF expression, and the area of the endometriotic implants in the mice models.  The study was an experiment designed. It has been conducted within the Department of Obstetrics Gynecology, Faculty of Medicine Diponegoro University and Faculty of Veterinary Medicine Airlangga University. Twenty-one mice were divided into three groups, i.e., the first group of mouse models was given Kebar extract 3 mg/day; the second group was assigned green tea extract 1.1 mg/day; therefore the third group was a control group contains the untreated endometriosis mice. Each treatment was given for fourteen days. MDA serum level was measured by specto-photometric examination, the area of the endometriotic implants was measured by computer tracing technique, whereas TNF-α and VEGF expression of endometriotic implants were measured by IHC using Rammele Scale Index (ImmunoReactive Score). The MDA serum levels of the groups treated with Kebar grass extract and green tea extract were significantly lower than the control group (0.09±0.022 mmol, 0.07±0.019 mmol, and 0.30±0.062 mmol, respectively; p=0.001). TNF-α expression of the groups supplied with each treatment also lower than the control groups (2.43±1.521, 3.66±1.422, and 7.26±2.898, respectively; p=0.002). However, VEGF expression was not significantly different between Kebar grass extract group, green tea group, and the control (4.34±2.402, 4.57±1.998, 7.40±3.495, respectively; p=0.089). Finally, the area of the endometriotic implants of the mice models administered with all treatment was smaller than the control group (0.01±0.025 mm2, 8.76±18.776 mm2, and 34.80±13.079 mm2, respectively; p=0.003). Conclusion: Kebar grass extract, as well as green tea extract administration to endometriosis model mice, resulted in lower MDA serum level and TNF-α expression, smaller the area of endometriotic implants compared, but not resulted in a significant difference of VEGF expression.


endometriotic implants; green tea extract; kebar grass extract; malondialdehyde; tumor necrosis factor alpha; vascular endothelial growth factor

Full Text:



Fritz MA, Speroff L. Endometriosis. In: Clinical gynecologic endocrinology and infertility. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2010. p. 1221–48.

Sekhon LH, Agarwal A. Endometriosis and oxidative stress. In: Agarwal A, Aziz N, Rizk B, editors. Studies on women’s health. New York: Humana Press; 2013. p. 149–67.

Kralickova M, Vetvicka V. Role of angiogenesis in endometriosis. Pathol Discov. 2016;4(1):1–5.

Rocha ALL, Reis FM, Taylor RN. Angiogenesis and endometriosis. Obstet Gynecol Int. 2013;2013:1–8.

Sourial S, Tempest N, Hapangama DK. Theories on the pathogenesis of endometriosis. Int J Reprod Med. 2014;2014:1–9.

Grund EM, Kagan D, Tran CA, Zeitvogel A, Starzinski-Powitz A, Nataraja S, et al. Tumor necrosis factor-a regulates inflammatory and mesenchymal responses via mitogen-activated protein kinase, p38, and nuclear factor B in human endometriotic epithelial cells. Mol Pharmacol. 2008;73:1394–404.

Sanchez G, Zubor P, Szunyogh N, Kajo K, Machalekova K, Biringer K, et al. [TNF-alpha serum levels in women with endometriosis: prospective clinical study]. Ces Gynekol. 2005;70(4):286–90.

Harada T, Taniguchi F, Izawa M, Ohama Y, Takenaka Y, Tagashira Y, et al. Apoptosis and endometriosis. Front Biosci. 2007;12:3140–51.

Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.

Sadsoeitoeboen PD. [Benefits of Kebar Grass extract (Biophytum petersianum Klotzsch) on the reproductive appearance of white female mice]. Vol. Pasca Sarj. [Bogor]: Institut Pertanian Bogor; 2005.

Alok S, Jain SK, Verma A, Kumar M, Mahor A, Sabharwal M. Herbal antioxidant in clinical practice: a review. Asian Pac J Trop Biomed. 2014;4(1):78–84.

Sembiring B, Darwati I. [Identification of chemical components of accession of Kebar Grass (Biophytum petersianum) from Papua and Java]. Obat BPTR dan, editor. 2014;25(1):37–44.

Sukarsono. [Profile of secondary metabolite content of medicinal plants Biophytum petersianum and Biophytum sensitivum]. J Gamma. 2012;6(1):69–76.

Man GCW, Xu H, Wang CC. Green Tea for Endometriosis. Chaudhury K, Chakravarty B, editors. Endometriosis. IntechOpen; 2012.

Hendarto H, Widjiati, Johari S. [Curcumin supplementation to improve oocyte maturation and results of in vitro fertilization in endometriosis mice]. Maj Obstet Ginekol. 2014;22(2):53–7.

Nowak M, Madej JA, Dziegiel P. Intensity of cox2 expression in cells of soft tissue fibrosacrcomas in dogs as related to grade of tumour malignancy. Bull Vet Inst Pulawy. 2007;51:275–9.

Gupta S, Chandra A, Kesavan S, Eapen D, Agarwal A. Oxidative Stress and the Pathogenesis of Endometriosis. In: Garcia-Velasco JA, Rizk BRMB, editors. Endometriosis: Current management and future trends. Cleveland: ClevelandClinic; 2010. p. 31–9.

Xu H, Lui WT, Chu CY, Ng PS, Wang CC, Rogers MS. Anti-angiogenic effects of green tea catechin on an experimental endometriosis mouse model. Hum Reprod. 2009;24(3):608–18.

Xu H, Becker CM, Lui WT, Chu CY, Davis TN, Kung AL, et al. Green tea epigallocatechin-3-gallate inhibits angiogenesis and suppresses vascular endothelial growth factor C/vascular endothelial growth factor receptor 2 expression and signaling in experimental endometriosis in vivo. Fertil Steril. 2011;96(4):1021–8.

Laschke MW, Schwender C, Scheuer C, Vollmar B, Menger MD. Epigallocatechin-3-gallate inhibits estrogen-induced activation of endometrial cells in vitro and causes regression of endometriotic lesions in vivo. Hum Reprod. 2008;23(1):2308–18.

Panjaitan BC, Sa’adi A, Hendarto H, Widjiati. Comparison of ovarial malondialdehyde (MDA) level between endometriosis rat given with and without curcumine supplementation. Maj Obstet Ginekol. 2012;20(1):30–4.

Sukina B, Prabowo GI, Suhartati S, Harianto N. [Green tea catechins (Camellia sinensis) against malondialdehyde and superoxide dismutase]. Indones J Clin Pathol Med Lab. 2013;19(2):92–7.

Artika FN, Susetyowati, Pramantara IDP, Lestari LA. [Effect of green tea extract (Camellia sinensis) to plasma malondialdehyde (MDA) level and hand grip strength of elderly]. 2016;13(2):59–66.

Greene AD, Lang SA, Kendziorski JA, Sroga-rios JM, Herzog TJ, Burns KA. Endometriosis : Where are We and Where are We Going ? 2017;152(3):1–29.

Wu M-H, Tsai S-J. Endometriosis and possible inflammation markers. Gynecol Minim Invasive Ther. 2015;4(3):61–7.

Rizzo MR, Abbatecola AM, Barbieri M, Vietri MT, Cioffi M, Grella R, et al. Evidence for anti-inflammatory effects of combined administration of vitamin E and C in older persons with impaired fasting glucose: impact on insulin action. J Am Coll Nutr. 2008;27(4):505–11.

Desai SJ, Prickril B, Rasooly A. Mechanisms of phytonutrient modulation of Cyclooxygenase-2 (COX-2) and inflammation related to cancer. Nutr Cancer. 2018;70(3):350–75.

Suganuma M, Takahashi A, Watanabe T, Iida K, Matsuzaki T, Yoshikawa HY, et al. Biophysical approach to mechanisms of cancer prevention and treatment with green tea catechins. Molecules. 2016;21(11):1–17.

Chen Z, Lin Z. Tea and human health: biomedical functions of tea active components and current issues. J Zhejiang Univ B. 2015;16(2):87–102.

Helieh SO. Chronic Inflammatory Diseases and Green Tea Polyphenols. Nutrients. 2017;9(6):561.

Lin Y-H, Chen Y-H, Chang H-Y, Au H-K, Tzeng C-R, Huang Y-H. Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies. Int J Mol Sci. 2018;19(8):2385.

Laschke MW, Menger MD. Anti-angiogenic treatment strategies for the therapy of endometriosis. Hum Reprod Update. 2012;18(6):682–702.

Schindler R, Mentlein† R. Flavonoids and Vitamin E Reduce the Release of the Angiogenic Peptide Vascular Endothelial Growth Factor from Human Tumor Cells. Journals Nutr. 2006;136:1477–2006.

Granese R, Bitto A, Polito F, Triolo O, Giordano D, Santamaria A, et al. Genistein reduces angiogenesis and apoptosis in women with endometrial hyperplasia. Bot Targets Ther. 2014;5(5):27–32.

Jehanara, Sutrisno, Santoso S. [Effect of Genistein on Decreasing Vascular Levels of Endothelial Growth Factor-A in Endometriosis Cell Culture]. Maj Obstet Ginekol. 2014;22(2):94–100.

Jackson LW, Schisterman EF, Dey-Rao R, Browne R, Armstrong D. Oxidative Stress and Endometrosis. Hum Reprod. 2005;20(7):2014–20.

Agarwal A, Gupta S, Agarwal A, Krajcir N, Alvarez JG. Role of oxidative stress in endometriosis. Reprod Biomed Online. 2006;13(1):126–34.

Das K, Bhattacharyya J. Antioxidant Functions of Green and Black Tea. In: Preedy VR, editor. Tea in Health and Disease Prevention. London: Elsevier; 2013. p. 521–8.

Santanam N, Kavtaradze N, Murphy A, Dominguez C, Parthasarathy S. Antioxidant supplementation reduces Eendometriosis related pelvic pain in humans. Transl Res J Lab Clin Med. 2014;161(3):189–95.

Erten OU, Ensari T gba A, Dilbaz B, Cakiroglu H, Altinbas SK, Çaydere M, et al. Vitamin C is effective for the prevention and regression of endometriotic implants in an experimentally induced rat model of endometriosis. Taiwan J Obstet Gynecol. 2016;55:251–7.

Tsuchiya M, Miura T, Hanaoka T, Iwasaki M, Sasaki H, Tanaka T, et al. Effect of soy isoflavones on endometriosis: interaction with estrogen receptor 2 gene polymorphism. Epidemiology. 2007;18(3):402–8.


Article Metrics

Abstract views : 1846 | views : 1831


  • There are currently no refbacks.

Copyright (c) 2019 Majalah Obat Tradisional

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

©Majalah Obat Tradisional (Traditional Medicine Journal)
 ISSN 2406-9086
Faculty of Pharmacy
Universitas Gadjah Mada