Centella asiatica Protects Against the Toxic Effects of Intracellular beta-amyloid Accumulation

Abstract

Centella asiatica has been used in Ayurvedic medicine as a nerve tonic and to enhance cognition. These effects have been confirmed experimentally in animals as well as human subjects. We have previously reported that the water extract of Centella asiatica (CAW) corrects β-amyloid (Aβ)-induced cognitive deficits in a transgenic mouse model of Alzheimer's disease and prevents Aβ toxicity in vitro. In this study we evaluated CAW's protective effects on Aβ-induced alterations in the MC65 neuroblastoma cell line, and identified potentially active compounds within the extract. In MC65 cells, CAW treatment reduced intracellular Aβ-induced cell death without changing Aβ accumulation. Concurrently, CAW attenuated Aβ-induced increases in total tau expression and site specific phosphorylation of tau. CAW also robustly increased expression of the antioxidant response gene NRF2 (nuclear factor erythroid-derived factor 2) as well as its target genes. While more studies are needed to confirm mechanisms, the effects on NRF2 suggest that the protective effect of CAW could be due, at least in part, to antioxidant actions. High performance liquid chromatography (HPLC) coupled to high-resolution mass spectrometry (HRMS) confirmed the absence in CAW of the triterpene compounds, asiatic acid, madecassic acid, asiaticoside and madecassoside, commonly found in the plant, and reported to have potent biological activities. Instead, using HRMS, several caffeoylquinic acids were determined to be present in CAW. Studies are currently underway to determine the efficacy of these compounds in the MC65 model system in order to evaluate their role in the neuroprotective effects of CAW.