Potential of Bitter Melon (Momordica charantia L.) Extract for Chronic Kidney Disease Based on In Vitro Study via TGF/SMADs Signaling, Antioxidant, Antiinflammation, Apoptosis Inducer Activities
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Keywords:
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Anti-inflammatory, Antioxidant, Apoptosis, Bitter Melon, Chronic Kidney Disease
Abstract
Chronic kidney disease (CKD) is a physiological abnormality in the kidneys whose prevalence is expected to continue to increase. On the other hand, Bitter melon (Momordica charantia L.) is known to have the potential to manage CKD. This study explores the compound content of M. charantia ethanol extract (MCEE) and its potential for CKD based on in vitro assays. To model chronic kidney disease (CKD), SV40 MES-13 (mouse glomerular mesangial) cells were exposed for 3 days to 20 mM glucose. After glucose induction, the cells were subjected with different concentrations of MCEE (Momordica charantia L. ethanolic extract). The chemical profile of MCEE was analyzed using LC/MS-MS. Cell viability was examined through the WST assay, while intracellular ROS and apoptosis levels were measured by flowcytometry. Colorimetry was used to analyze SOD, MDA, and CAT levels. ELISA was used to analyze inflammatory proteins (TGF-β 1, IL-6, TNF-α, IL-1β ) levels. Meanwhile, the relative gene expression of SMAD-2, SMAD-3, SMAD-4, SMAD-7 was examined through qRT-PCR. The results exhibited that MCEE contains cucurbitane p-coumaric, ferulic acid, caffeic acid, gallic acid, chlorogenic acid, and epicatechin. MCEE was also known to be non-toxic to SV40 MES-13 cells. In addition, MCEE reduced intracellular ROS levels, MDA, necrosis levels, and inflammatory proteins, while also regulating SMAD-2, SMAD-3, and SMAD-4 gene expression. MCEE increased levels of CAT, and SOD, and regulated SMAD-7 gene expression in the CKD cells model. The most effective MCEE is MCEE 50 μg/mL. MCEE demonstrated potential as a CKD treatment based on in vitro studies through TGF/SMADs signaling activity, antioxidant, anti-inflammatory, and apoptosis inducer.
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Han, H., A. Cao, L. Wang, H. Guo, Y. Zang, Z. Li, and W. Peng (2017). Huangqi Decoction Ameliorates Streptozotocin-Induced Rat Diabetic Nephropathy Through Antioxidant and Regulation of the TGF-MAPK/PPAR-???? Signaling. Cellular Physiology and Biochemistry, 42(5); 1934–1944.
Hidayat, M., S. Prahastuti, E. Afifah, W. Widowati, M. Yusuf, and K. Hasan (2022). The Role of Green Peas Protein Hydrolysate in TGF/SMAD Signaling to Prevent Renal Fibrosis. Journal of King Saud University-Science, 34(4); 101920.
Hill, N. R., S. T. Fatoba, J. L. Oke, J. A. Hirst, C. A. O’Callaghan, D. S. Lasserson, and F. R. Hobbs (2016). Global Prevalence of Chronic Kidney Disease–A Systematic Review and Meta-Analysis. PloS One, 11(7); e0158765.
Huang, H. T., L. J. Zhang, H. C. Huang, S. Y. Hwang, C. L. Wu, Y. C. Lin, and Y. H. Kuo (2020). Cucurbitane-Type Triterpenoids From the Vines of Momordica charantia and Their Anti-Inflammatory Activities. Journal of Natural Products, 83(5); 1400–1408.
Hustrini, N. M., E. Susalit, and J. I. Rotmans (2022). Prevalence and Risk Factors for Chronic Kidney Disease in Indonesia: An Analysis of the National Basic Health Survey 2018. Journal of Global Health, 12.
Irazabal, M. V. and V. E. Torres (2020). Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease. Cells, 9(6); 1342.
Jin, Q., T. Liu, Y. Qiao, D. Liu, L. Yang, H. Mao, and Y. Zhan (2023). Oxidative Stress and Inflammation in Diabetic Nephropathy: Role of Polyphenols. Frontiers in Immunology, 14; 1185317.
Kimura, K., T. Hosoya, S. Uchida, M. Inaba, H. Makino, S. Maruyama, and Y. Ehara (2018). Febuxostat Therapy for Patients With Stage 3 CKD and Asymptomatic Hyperuricemia: A Randomized Trial. American Journal of Kidney Diseases, 72(6); 798–810.
Klemis, V., H. Ghura, G. Federico, C. Würfel, A. Bentmann, N. Gretz, and I. A. Nakchbandi (2017). Circulating Fibronectin Contributes to Mesangial Expansion in a Murine Model of Type 1 Diabetes. Kidney International, 91(6); 1374–1385.
Kovesdy, C. P. (2022). Epidemiology of Chronic Kidney Disease: An Update 2022. Kidney International Supplements, 12(1); 7–11.
Landau, S. I., X. Guo, H. Velazquez, R. Torres, E. Olson, R. Garcia-Milian, and R. Safirstein (2019). Regulated Necrosis and Failed Repair in Cisplatin-Induced Chronic Kidney Disease. Kidney International, 95(4); 797–814.
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Malinda, K., H. Sutanto, and A. Darmawan (2017). Characterization and Antioxidant Activity of Gallic Acid Derivative. In AIP Conference Proceedings, volume 1904. AIP Publishing.
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Authors
Prahastuti, S., Rahardja, F., Wargasetia, T. L. ., Zahiroh, F. H., Sabrina, A. H. N. ., Kusuma, H. S. W. ., Azis, R., Hadiprasetyo, D. S. ., Ningrum, S. R. R. ., Widowati, W., & Sarwono, S. (2025). Potential of Bitter Melon (Momordica charantia L.) Extract for Chronic Kidney Disease Based on In Vitro Study via TGF/SMADs Signaling, Antioxidant, Antiinflammation, Apoptosis Inducer Activities. Science and Technology Indonesia, 10(2), 538–551. https://doi.org/10.26554/sti.2025.10.2.538-551
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