Pharmacological Activities of Centella asiatica: A Systematic Review of Preclinical and Clinical Evidence on Cardiovascular, Neurological, Antioxidant, and Anti-inflammatory Effects.

Centella asiatica (L.) (Gotu Kola) is a medicinal herb traditionally used in Asia for cognitive enhancement, wound healing, and systemic disorders. This systematic review appraises preclinical and clinical evidence on its cardiovascular and neurological effects. Following PRISMA 2020, we searched PubMed, ScienceDirect, Scopus, Embase, and ClinicalTrials.gov (to June 2026) for studies of whole-plant extracts or bioactive compounds (asiatic acid, asiaticoside, madecassoside, madecassic acid, caffeoylquinic acids) in vitro, in animals, or in humans, excluding dermatological studies, reviews, and articles lacking methods. Sixty-two studies met criteria: 54 preclinical and eight clinical trials, assessed using SYRCLE, an in vitro checklist, and Cochrane RoB 2. Preclinically, C. asiatica modulated ischemia-reperfusion injury, reduced doxorubicin-induced cardiotoxicity, improved cognitive deficits in Alzheimer's and Parkinson's models, and showed antidepressant-like effects, via Nrf2/HO-1 antioxidant activation and NF-κB/MAPK anti-inflammatory suppression. Clinical evidence was mixed: Gotu Kola matched or exceeded folic acid for poststroke vascular cognitive impairment, and three trials of a standardized triterpenic fraction (TTFCA) improved microcirculation in venous hypertensive and diabetic microangiopathy; however, a type 2 diabetes trial found no significant effect on glycated hemoglobin, glucose, or LDL cholesterol, a mild cognitive impairment trial found no added benefit over exercise alone, and a Phase 1 safety trial is ongoing. C. asiatica shows preclinical promise as a multitarget cardiovascular and neurological agent, but clinical evidence remains limited and inconsistent, compounded by an 800-fold preclinical dosing range, variable treatment durations, and geographic concentration (47% from one country). Larger, standardized, multiregion trials targeting these outcomes are needed before therapeutic claims are warranted.