Phytotherapy for ageing-related multimorbidity: Systems-level insights into Centella asiatica in diabetes and Alzheimer's Disease.

BACKGROUND: The increasing burden of age-related illnesses underscores the urgent necessity for integrative treatment approaches that simultaneously address the complex connections between metabolic and neurodegenerative disorders. Diabetes mellitus (DM) and Alzheimer's disease (AD) are strongly interconnected through shared pathological mechanisms. Plant-based therapeutics with their rich diversity of multitarget bioactive compounds are able to compromise such a complex network. Centella asiatica (l.) Urb. (C. asiatica), A medicinal herb, it has garnered significant attention for its metabolic and neuroprotective activities in ethnopharmacology, as well as preclinical and clinical studies. PURPOSE: In this study, we employ a computational approach to elucidate the key bioactive constituents of C. asiatica and their ability to modulate shared pathological mechanisms linking DM and AD. Provide a scientific rationale for its use as a multitarget phyto-therapeutic candidate against ageing-associated comorbidities. METHODS: Relevant keywords were used to search databases Scopus, Science Direct, PubMed, Google Scholar and WOS. To gather the scientific evidence of its phytoconstituents, anti-diabetic activity and anti-Alzheimer's activity. Further, a network pharmacology-based approach was adopted. RESULTS: From the identified phytoconstituents, fifty-four have favourable oral bioavailability, targeting 486 proteins. Venn interaction revealed 404 genes are cross-linked among C. asiatica, DM, and AD. Network pharmacology and enrichment analysis suggested that the PI3K-Akt signalling pathway is the key regulatory axis. CONCLUSION: C. asiatica demonstrates potential as a multi-target phyto-therapeutic agent for managing interconnected ageing disorders, i.e., DM and AD, through modulation of the PI3K-Akt signalling pathway.