Computational Exploration of Tomato's Bioactive Compounds as Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent

Year 2026, Volume: 30 Issue: 1, 106 - 116, 11.01.2026

Sekararum Narwasyhu , Titin Andri Wihastuti , Turhadi Turhadi , Nia Kurnianingsih , Fatchiyah Fatchiyah

https://doi.org/10.12991/jrespharm.1642714

https://izlik.org/JA63DR55MJ

Abstract

Tomato (Solanum lycopersicum) is a plant native to the tropics and has been widely recognized for its various health benefits. Previous studies have revealed that tomato extracts have the ability to treat obesity. This study was designed to explore the potential of bioactive compounds from S. lycopersicum in suppressing obesity through inhibiting the peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling pathway. S. lycopersicum bioactive compounds were screened for bioactivity, toxicity, and drug similarity. The STRING database was employed to predict protein targets, which was followed by functional annotation analysis. Potential binding sites between bioactive compounds and target proteins, including CREB-binding protein (CREBBP), PPAR-γ, and Sirtuin1 (SIRT1), were determined via molecular docking. Molecular dynamics simulations were conducted using Yet Another Scientific Artificial Reality Application (YASARA) to evaluate the stability of ligand-protein interactions under physiological conditions. Owing to its toxicological profile, bioactivity, and similarity to drugs, kaempferol has become a potential choice for countering anti-obesity. Molecular docking experiments showed that kaempferol can bind to CREBBP, PPAR-γ, and SIRT1. These results were corroborated by molecular dynamics simulations, which demonstrated persistent interactions between kaempferol and the target proteins as indicated by ligand movement, hydrogen bonding patterns, and root mean square deviation backbone analysis. This study concludes that tomato-derived compounds, especially kaempferol, may have therapeutic effects on obesity by acting as PPAR-γ antagonists

Keywords

Kaempferol , Obesity , PPAR-γ , Tomato

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