Alshehade, Salah Abdulrazak and Zarzour, Raghdaa Hamdan Al and Murugaiyah, Vikneswaran and Lim, Sharoen Yu Ming and El-Refae, Huda Ghaleb and Alshawsh, Mohammed Abdullah (2022) Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches. Saudi Pharmaceutical Journal, 30 (11). pp. 1572-1588. ISSN 1319-0164, DOI https://doi.org/10.1016/j.jsps.2022.09.001.
Full text not available from this repository.Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syn-drome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accu-mulation and to further use the computational systems pharmacology approach to identify the pharma-cokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cyto-toxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive com-pounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted tar-gets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial b-oxidation, inflammatory signalling pathways, insulin sig-nalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computa-tional systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya, Malaysia ST070-2021, Ministry of Higher Education Malaysia Fundamental Research Grant Scheme 304/PFARMASI/6315201, Universiti Sains Malaysia ST070-2021, FRGS/1/2021/SKK0/USM/02/27 |
| Uncontrolled Keywords: | Orthosiphon aristatus; Orthosiphon stamineus; Medicinal plant; Systems pharmacology; Non-alcoholic fatty liver disease; Cellular target; Pathway enrichment analysis; Protein-protein interaction; Molecular docking; Oxidative stress; Inflammation |
| Subjects: | R Medicine > RC Internal medicine R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 17 Oct 2023 04:46 |
| Last Modified: | 24 Oct 2023 04:52 |
| URI: | http://eprints.um.edu.my/id/eprint/40329 |
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