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J Herbmed Pharmacol. 2024;13(4): 630-639.
doi: 10.34172/jhp.2024.52544
  Abstract View: 83
  PDF Download: 45

Original Article

Computational investigation of Pluchea indica mechanism targeting peroxisome proliferator-activated receptor gamma

Purnawan Pontana Putra 1* ORCID logo, Raden Bayu Indradi 2 ORCID logo, Tegar Achsendo Yuniarta 3 ORCID logo, Dini Hanifa 1 ORCID logo, Mokhamad Fahmi Rizki Syaban 4 ORCID logo, Netty Suharti 5 ORCID logo

1 Departement of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Andalas, Padang, 25163, Indonesia
2 Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
3 Departement of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Surabaya, Surabaya, 60293, Indonesia
4 Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia
5 Departement of Biology Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, 25163, Indonesia
*Corresponding Author: Purnawan Pontana Putra, Email: purnawanpp@phar.unand.ac.id

Abstract

Introduction: Pluchea indica is known to have diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. However, there is a pressing need to thoroughly investigate the molecular interactions between P. indica compounds and peroxisome proliferator-activated receptor gamma (PPARG). This study aimed to elucidate the molecular mechanisms behind P. indica and PPARG, and its potential implications for diabetes mellitus.

Methods: The computational investigation employed Pharmacological Network pharmacology, homology modeling, deep learning docking, and molecular dynamics to explore the active compounds and targets within P. indica against the PPARG.

Results: Three active compounds were identified namely pinoresinol, syringaresinol, and plucheoside A, all of which complied with the Lipinski rule of five. The deep learning-based pose scores were determined as follows: Pinoresinol 0.55, syringaresinol 0.32, and plucheoside A 0.44. Additionally, protein-protein interactions were observed with PPARG and associated with the PPAR signaling pathway. Molecular dynamics simulation analysis showed the stability of the three compounds over a 100 ns period. Free energy calculations using Molecular Mechanics-Generalized Born and Surface Area (MM-GBSA) yielded ΔG values of -44.39 kcal/mol, -51.83 kcal/mol, and -40.27 kcal/mol for pinoresinol, syringaresinol, and plucheoside A, respectively.

Conclusion: Pluchea indica might be developed to treat various diseases, particularly those involving the PPARG signaling pathway. It suggests the possibility of being developed as a focused medication for diabetes.


Implication for health policy/practice/research/medical education:

Three active compounds found in Pluchea indica that could be developed into orally absorbable drugs, showing promise in treating conditions like diabetes by targeting PPARG. The study suggests that these compounds have the potential to become targeted medications, as indicated by their favorable binding energies and stability in molecular dynamics, supported further by free energy calculations.

Please cite this paper as: Putra PP, Indradi RB, Yuniarta TA, Hanifa D, Syaban MFR, Suharti N. Computational investigation of Pluchea indica mechanism targeting peroxisome proliferator-activated receptor gamma. J Herbmed Pharmacol. 2024;13(4):630-639. doi: 10.34172/jhp.2024.52544.

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Submitted: 16 Mar 2024
Accepted: 29 May 2024
ePublished: 01 Oct 2024
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