Integrative network pharmacology, transcriptomics, and molecular docking identify candidate Centella asiatica constituents and targets in neurodegenerative diseases.
Integrative network pharmacology, transcriptomics, and molecular docking identify candidate Centella asiatica constituents and targets in neurodegenerative diseases.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Zunyi, CN · Author affiliation
Department of Clinical Nutrition, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.Location evidence
MY · Author affiliation · country only
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.Location evidence
Toyama, JP · Author affiliation
Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.Location evidence
Cheras, MY · Author affiliation
M Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman Cheras, Kajang, Selangor, Malaysia.Location evidence
Kajang, MY · Author affiliation
M Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman Cheras, Kajang, Selangor, Malaysia.Location evidence
Jakarta, ID · Author affiliation
Fakultas Kedokteran, Universitas Pembangunan Nasional "Veteran" Jakarta, Jakarta, Indonesia.Location evidence
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Original abstract
BACKGROUND: Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), are progressive disorders with limited therapeutic options. Centella asiatica (C. asiatica), a medicinal and edible plant, has been reported to exert neuroprotective and anti-neuroinflammatory properties. Yet, the mechanisms underlying its effects against neurodegenerative diseases remain largely unclear. METHODS: We employed an integrative strategy combining network pharmacology, transcriptomic analyses, machine learning and molecular docking to prioritize disease-associated molecular networks and candidate compound-target relationships in AD, PD and HD. RESULTS: Sixteen candidate constituents of C. asiatica met the predefined drug-likeness, gastrointestinal absorption and blood-brain barrier permeability criteria, yielding 370 unique predicted targets. Disease-gene mining identified 983 AD-associated genes, 1,103 PD-associated genes, and 3,316 HD-associated genes. Integration of compound targets, disease-associated genes, and transcriptomic profiles prioritized five hub genes in PD (CCKAR, MAPK8, PSEN2, SLC6A3, and TH), four in AD (APP, PGK1, PIK3CA, and TTR), and four in HD (CHRND, HSP90AA1, PRKCQ, and TH). Enrichment analyses highlighted disease-relevant processes involving neurotransmitter signalling, cAMP and calcium pathways, MAPK-related responses and inflammatory regulation. ROC analyses provided additional support for the discriminatory performance of the prioritized genes in independent datasets, whereas molecular docking identified favourable predicted Vina docking scores and structurally plausible interactions between selected compounds and hub targets. CONCLUSION: This integrative computational analysis prioritizes candidate C. asiatica constituents, putative disease-associated targets, and molecular pathways in AD, PD, and HD. The findings provide a foundation for subsequent biochemical, cellular, and in vivo validation.