Centella asiaticaExtract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action

Abstract

Centella asiatica (CA), commonly named gotu kola, is an Ayurvedic herb used to enhance memory and nerve function. To investigate the potential use of CA in Alzheimer's disease (AD), we examined the effects of a water extract of CA (GKW) in the Tg2576 mouse, a murine model of AD with high β-amyloid burden. Orally administered GKW attenuated β-amyloid-associated behavioral abnormalities in these mice. In vitro, GKW protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity induced by exogenously added and endogenously generated β-amyloid, respectively. GKW prevented intracellular β-amyloid aggregate formation in MC65 cells. GKW did not show anticholinesterase activity or protect neurons from oxidative damage and glutamate toxicity, mechanisms of current AD therapies. GKW is rich in phenolic compounds and does not contain asiatic acid, a known CA neuroprotective triterpene. CA thus offers a unique therapeutic mechanism and novel active compounds of potential relevance to the treatment of AD.

Medicinal Property of Gotu kola (Centella asiatica) from the Selection of Traditional Applications to the Novel Phytotherapy

“…In various studies testing cognitive improvements of rats and standard shuttle box, step-through paradigm, elevated plus maze and passive avoidance tests, C. asiatica improved learning and memory [10]. When aqueous extracts of C. asiatica at doses of 100-300 mg/kg per day were distributed to newborn mice from 15 days old to 30 days old, learning and spatial memory were improved without influencing motor functioning skills [10].…”

“…When aqueous extracts of C. asiatica at doses of 100-300 mg/kg per day were distributed to newborn mice from 15 days old to 30 days old, learning and spatial memory were improved without influencing motor functioning skills [10]. Soumyanath et al reported that doses of C. asiatica influenced the cell nerves of the pyramidal cells in the prefrontal cortex, the hippocampus, and other areas, in newborn and adult mice and rats [10]. Soumyanath et al suggest that results from these studies presents aqueous extract of C. asiatica as lowering the degenerative impairments of memory, learning and aging in relation to Alzheimer's disease [10].…”

“…Soumyanath et al reported that doses of C. asiatica influenced the cell nerves of the pyramidal cells in the prefrontal cortex, the hippocampus, and other areas, in newborn and adult mice and rats [10]. Soumyanath et al suggest that results from these studies presents aqueous extract of C. asiatica as lowering the degenerative impairments of memory, learning and aging in relation to Alzheimer's disease [10].…”

“…To test characteristics similar to Alzheimer's disease, the mutant human amyloid precursor protein (APP) was injected in each mouse. APP produces cortical β-amyloid (Aβ) plaques similar to Alzheimer's disease pathology [10]. Fifteen Tg2576 mice and twenty wild-type twenty-month-old female mice organized according to genotype.…”

“…Spatial memory impairment in Tg2576 mice progressed with C. asiatica treatment. The progression was correlated with the appearance of Aβ plaques [10].…”