International Journal of Molecular and Cellular Medicine

en An In Silico Study of Transforming Growth Factor-β Inhibitors: A Potential Target for Diabetic Nephropathy Treatment with Active Compounds from the Active Fraction of Physalis angulata Bioinformatic Bioinformatic Original Article Original Article Transforming growth factor beta (TGF-β) initiates epithelial-mesenchymal transition (EMT) in tubular and glomerular epithelial cells, resulting in excessive production and deposition of extracellular matrix through its interaction with TGF-β receptors, which play a crucial role in TGF-β signaling involving two receptor types, namely TGF-β type I (TβRI) and type II (TβRII). EMT contributes to the pathogenesis of interstitial renal fibrosis, a marker of end-stage kidney disease. This study aimed to identify the bioactive compounds in the active fraction of P. angulata and evaluate their ability to inhibit the TGF-β activity and their potential as drug candidates. The active components in the active fraction of P. angulata were analyzed using gas chromatography-mass spectrometry (GC-MS). The bioactive compound structures were obtained from the PubChem database, while the protein targets, TβRI and TβRII, were retrieved from the Protein Data Bank (PDB). The molecular docking analyses were performed using PyRx 0.8 and Discovery Studio. SwissADME was used to evaluate ligand properties and druglikeness. Three dominant active compounds were identified, namely palmitic acid, campesterol, and stigmasterol. In silico studies demonstrated strong energy bonds existed between TβRI and palmitic acid, campesterol, stigmasterol, and SB431542 with binding energy values of -5.7, -10, -9.4, and -10.9 kcal/mol, respectively. Similarly, they strongly bound to TβRII with binding energy values of -5.2, -7.1, -7.5, and -6.1 kcal/mol, respectively. All compounds meet Lipinski’s criteria for druglikeness. Among the identified active compounds, campesterol exhibited the highest affinity for TβRI, while stigmasterol exhibited a strong affinity for TβRII. These findings suggested that the three compounds have potential as drug candidates.   Diabetic nephropathy, transforming growth factor beta, TGF-β inhibitor, Physalis angulata 234 247 http://ijmcmed.org/browse.php?a_code=A-10-7500-1&slc_lang=en&sid=1 Ika Rahayu ikarahayu@mail.ugm.ac.id 100319475328460032721 100319475328460032721 No Doctoral Program of the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia. Nur Arfian nur_arfian@ugm.ac.id 100319475328460032722 100319475328460032722 Yes Department of Anatomy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia . Kris Herawan Timotius kh_timotius@ukrida.ac.id 100319475328460032723 100319475328460032723 No Department of Biochemistry, Faculty of Medicine and Health Sciences, Universitas Kristen Krida Wacana, Indonesia. Mae Sri Hartati Wahyuningsih maeshw@ugm.ac.id 100319475328460032724 100319475328460032724 No Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.