Depression-Related Mechanistic and Translational Evidence for Centella asiatica and Its Triterpenoids: A Scoping Review.

BACKGROUND: Depression is a multifactorial psychiatric disorder involving monoaminergic, neurotrophic, inflammatory, oxidative, and stress-response pathways. Centella asiatica and its triterpenoids have demonstrated neuroprotective and stress-modulating properties, but depression-focused evidence remains fragmented. OBJECTIVE: The aim of this scoping review was to map the available evidence on C. asiatica, its standardized extracts, and its bioactive triterpenoids in relation to depression-related outcomes and mechanisms. METHODS: A protocol was registered before formal screening, full-text assessment, data charting, and evidence synthesis (INPLASY202670003). Scopus, PubMed/MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched from inception to 2 July 2026. Eligible studies included human, animal, cell-based, and ex vivo studies reporting depression, depressive-like behavior, antidepressant-like effects, or mechanisms explicitly linked to depression-related pathophysiology. Two reviewers independently screened the identified records and charted the data using a standardized form, with disagreements resolved through consensus or consultation with a third reviewer. The findings were synthesized descriptively and narratively. RESULTS: A total of 14 studies published between 2008 and 2025 were included, comprising 13 preclinical studies and 1 open-label human study. No eligible cell-based or ex vivo studies were identified. The included studies primarily examined C. asiatica extracts and isolated triterpenoids, particularly asiaticoside and asiatic acid. Most studies reported favorable depression-related or antidepressant-like findings. The principal reported mechanisms involved BDNF/CREB-related signaling and neuroplasticity, monoaminergic regulation, attenuation of neuroinflammation and oxidative stress, and modulation of the hypothalamic-pituitary-adrenal axis. However, the evidence base is heterogeneous and predominantly derived from animal models. CONCLUSIONS: The available evidence supports the biological plausibility and preclinical antidepressant-like activity of C. asiatica and its triterpenoids; however, the evidence remains insufficient to establish clinical efficacy in humans. Future studies should prioritize standardized preparations, dose justification, pharmacokinetic and safety evaluation, validated depression-specific outcomes, and rigorously controlled clinical trials.