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

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

doi:10.12991/jrespharm.1642714

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

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

References

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Details

Primary Language

English

Subjects

Basic Pharmacology

Journal Section

Research Article

Authors

Sekararum Narwasyhu
0009-0007-5814-9632
Indonesia

Titin Andri Wihastuti
0000-0001-6476-0541
Indonesia

Turhadi Turhadi
0000-0003-4906-3769
Indonesia

Nia Kurnianingsih
0000-0003-4497-9487
Indonesia

Fatchiyah Fatchiyah ^*
0000-0001-6241-9665
Indonesia

Publication Date

January 11, 2026

Submission Date

February 19, 2025

Acceptance Date

May 15, 2025

Published in Issue

Year 2026 Volume: 30 Number: 1

DOI

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

IZ

https://izlik.org/JA63DR55MJ

Cite

RIS / Bibtex

APA

Narwasyhu, S., Wihastuti, T. A., Turhadi, T., Kurnianingsih, N., & Fatchiyah, F. (2026). Computational Exploration of Tomato’s Bioactive Compounds as Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent. Journal of Research in Pharmacy, 30(1), 106-116. https://doi.org/10.12991/jrespharm.1642714

AMA

1.Narwasyhu S, Wihastuti TA, Turhadi T, Kurnianingsih N, Fatchiyah F. Computational Exploration of Tomato’s Bioactive Compounds as Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent. J. Res. Pharm. 2026;30(1):106-116. doi:10.12991/jrespharm.1642714

Chicago

Narwasyhu, Sekararum, Titin Andri Wihastuti, Turhadi Turhadi, Nia Kurnianingsih, and Fatchiyah Fatchiyah. 2026. “Computational Exploration of Tomato’s Bioactive Compounds As Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent”. Journal of Research in Pharmacy 30 (1): 106-16. https://doi.org/10.12991/jrespharm.1642714.

EndNote

Narwasyhu S, Wihastuti TA, Turhadi T, Kurnianingsih N, Fatchiyah F (January 1, 2026) Computational Exploration of Tomato’s Bioactive Compounds as Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent. Journal of Research in Pharmacy 30 1 106–116.

IEEE

[1]S. Narwasyhu, T. A. Wihastuti, T. Turhadi, N. Kurnianingsih, and F. Fatchiyah, “Computational Exploration of Tomato’s Bioactive Compounds as Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent”, J. Res. Pharm., vol. 30, no. 1, pp. 106–116, Jan. 2026, doi: 10.12991/jrespharm.1642714.

ISNAD

Narwasyhu, Sekararum - Wihastuti, Titin Andri - Turhadi, Turhadi - Kurnianingsih, Nia - Fatchiyah, Fatchiyah. “Computational Exploration of Tomato’s Bioactive Compounds As Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent”. Journal of Research in Pharmacy 30/1 (January 1, 2026): 106-116. https://doi.org/10.12991/jrespharm.1642714.

JAMA

1.Narwasyhu S, Wihastuti TA, Turhadi T, Kurnianingsih N, Fatchiyah F. Computational Exploration of Tomato’s Bioactive Compounds as Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent. J. Res. Pharm. 2026;30:106–116.

MLA

Narwasyhu, Sekararum, et al. “Computational Exploration of Tomato’s Bioactive Compounds As Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent”. Journal of Research in Pharmacy, vol. 30, no. 1, Jan. 2026, pp. 106-1, doi:10.12991/jrespharm.1642714.

Vancouver

1.Sekararum Narwasyhu, Titin Andri Wihastuti, Turhadi Turhadi, Nia Kurnianingsih, Fatchiyah Fatchiyah. Computational Exploration of Tomato’s Bioactive Compounds as Potential CREBBP, PPAR-γ, and SIRT1 Antagonists for Candidates of Obesity Therapeutic Agent. J. Res. Pharm. 2026 Jan. 1;30(1):106-1. doi:10.12991/jrespharm.1642714