An ancient Ayurvedic remedy, Centella asiatica (L.) Urb. (Apiaceae), also known by the synonym Hydrocotyle asiatica L., is reputed to restore youth, memory and longevity. In Sanskrit, and commonly as an herbal product, it is known as ‘gotu kola’. An Ayurvedic formulation composed of four herbs including Centella asiatica, is used to retard age and prevent dementia, and the herb combined with milk is given to improve memory. In TCM Centella asiatica has been used for various disorders, such as traumatic diseases, and for combating physical and mental exhaustion. The essential oil from Centella asiatica leaf contains monoterpenoids, including bornyl acetate, α-pinene, β-pinene and γ-terpinene, all of which are reported to inhibit acetylcholinesterase. However, monoterpenoid acetylcholinesterase inhibitors are weak compared to the anti-cholinesterase alkaloid, physostigmine. In view of the relatively weak anti-cholinesterase activity of monoterpenoids reported to date, it is unlikely that they would be therapeutically effective in cognitive disorders.
The pharmacological basis to explain the reputed antiamnesic effects of Centella asiatica has been explored in a number of studies. An alcoholic extract of Centella asiatica was tranquillising in rats, an activity that was attributed to a triterpenoid, brahmoside. Further studies showed the extract of Centella asiatica leaf to be sedative, antidepressant and potentially cholinomimetic in vivo, and asiaticoside, a triterpenoid saponin from Centella asiatica, is a reported anxiolytic. These findings suggest that Centella asiatica may be appropriate to treat symptoms of depression and anxiety in Alzheimer’s disease, and that it may also influence cholinergic activity and, thus, cognitive function. Cognitive enhancing effects have been observed in rats following oral administration of an aqueous extract of Centella asiatica; this effect was associated with an antioxidant mechanism in the CNS. Further evidence for the antioxidant benefits of Centella asiatica extract were observed when it was administered orally to rats and was shown to protect the rat brain against age-related oxidative damage. Knowledge regarding the compounds responsible for these effects is lacking, although phenolic compounds in Centella asiatica have been correlated with antioxidative activity in vitro. An aqueous extract of this plant has also been shown to decrease seizures and prevent cognitive impairment in an animal model for epilepsy.
Alterations in other neurotransmitter systems have been associated with Alzheimer’s disease pathology. Interestingly, an aqueous extract of Centella asiatica leaf modulated dopamine, 5-hydroxytryptamine (5-HT) and noradrenaline systems in rat brain and improved learning and memory processes in vivo. Glutamate may induce neuronal degeneration by overstimulation of NMDA receptors, and memantine, an NMDA receptor antagonist, is therapeutically effective in Alzheimer’s disease patients. The triterpenoid asiatic acid (found in Centella asiatica) and its derivatives have been shown to protect cortical neurons from glutamate-induced excitotoxicity in vitro. A neuroprotective action may contribute to changes in the dendritic morphology of neurons in the CNS. This has been suggested by a study in which stimulation of neuronal dendritic growth in hippocampal neurons was observed following administration of leaf extracts of Centella asiatica to neonatal rat pups. Components in Centella asiatica including asiatic acid have also been suggested to accelerate repair of damaged neurons. This action, perhaps in conjunction with other observed biological activities relevant to the alleviation of cognitive dysfunction, could explain the basis for the reputed memory-enhancing effects of this plant.