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.