PMID- 36465851
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221206
IS  - 1319-0164 (Print)
IS  - 2213-7475 (Electronic)
IS  - 1319-0164 (Linking)
VI  - 30
IP  - 11
DP  - 2022 Nov
TI  - Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver 
      disease: Insights from systems pharmacology and molecular docking approaches.
PG  - 1572-1588
LID - 10.1016/j.jsps.2022.09.001 [doi]
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications 
      of a metabolic syndrome 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 accumulation and to further use the computational systems 
      pharmacology approach to identify the pharmacokinetic 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 
      cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 
      cells. The bioactive compounds 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 targets. 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 beta-oxidation, inflammatory 
      signalling pathways, insulin signalling, 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 computational 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.
CI  - (c) 2022 The Author(s).
FAU - Alshehade, Salah Abdulrazak
AU  - Alshehade SA
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains 
      Malaysia, Penang 11800, Malaysia.
AD  - Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 
      50603, Malaysia.
FAU - Al Zarzour, Raghdaa Hamdan
AU  - Al Zarzour RH
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains 
      Malaysia, Penang 11800, Malaysia.
AD  - Department of Pharmacology, Faculty of Pharmacy, Arab International University 
      (AIU), Damascus, Syria.
FAU - Murugaiyah, Vikneswaran
AU  - Murugaiyah V
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains 
      Malaysia, Penang 11800, Malaysia.
FAU - Lim, Sharoen Yu Ming
AU  - Lim SYM
AD  - Division of Biomedical Sciences, School of Pharmacy, University of Nottingham 
      Malaysia, Semenyih 43500, Malaysia.
FAU - El-Refae, Huda Ghaleb
AU  - El-Refae HG
AD  - College of Pharmacy, Al Ain University, Al Ain 64141, United Arab Emirates.
FAU - Alshawsh, Mohammed Abdullah
AU  - Alshawsh MA
AD  - Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 
      50603, Malaysia.
LA  - eng
PT  - Journal Article
DEP - 20220914
PL  - Saudi Arabia
TA  - Saudi Pharm J
JT  - Saudi pharmaceutical journal : SPJ : the official publication of the Saudi 
      Pharmaceutical Society
JID - 9705695
PMC - PMC9715956
OTO - NOTNLM
OT  - Cellular target
OT  - Inflammation
OT  - Medicinal plant
OT  - Molecular docking
OT  - Non-alcoholic fatty liver disease
OT  - Orthosiphon aristatus
OT  - Orthosiphon stamineus
OT  - Oxidative stress
OT  - Pathway enrichment analysis
OT  - Protein-protein interaction
OT  - Systems pharmacology
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2022/12/06 06:00
MHDA- 2022/12/06 06:01
PMCR- 2022/09/14
CRDT- 2022/12/05 03:49
PHST- 2022/05/17 00:00 [received]
PHST- 2022/09/03 00:00 [accepted]
PHST- 2022/12/05 03:49 [entrez]
PHST- 2022/12/06 06:00 [pubmed]
PHST- 2022/12/06 06:01 [medline]
PHST- 2022/09/14 00:00 [pmc-release]
AID - S1319-0164(22)00223-7 [pii]
AID - 10.1016/j.jsps.2022.09.001 [doi]
PST - ppublish
SO  - Saudi Pharm J. 2022 Nov;30(11):1572-1588. doi: 10.1016/j.jsps.2022.09.001. Epub 
      2022 Sep 14.