Centella asiatica Attenuates Amyloid-beta-Induced Oxidative Stress and Mitochondrial Dysfunction

作者：Gray Nora E^*; Sampath Harini; Zweig Jonathan A; Quinn Joseph F; Soumyanath Amala

来源：Journal of Alzheimer's Disease, 2015, 45(3): 933-946.

DOI：10.3233/JAD-142217

• Amyloid-beta toxicity
• calcium homeostasis
• Centella asiatica
• mitochondrial dysfunction
• neuroprotection
• reactive oxygen species

Background: We previously showed that a water extract of the medicinal plant Centella asiatica (CAW) attenuates amyloid-beta (A beta)-induced cognitive deficits in vivo, and prevents A beta-induced cytotoxicity in vitro. Yet the neuroprotective mechanism of CAW is unknown.
Objective: The goal of this study was to identify biochemical pathways altered by CAW using in vitro models of A beta toxicity.
Methods: The effects of CAW on aberrations in antioxidant response, calcium homeostasis, and mitochondrial function induced by A beta were evaluated in MC65 and SH-SY5Y neuroblastoma cells.
Results: CAW decreased intracellular reactive oxygen species and calcium levels elevated in response to A beta, and induced the expression of antioxidant response genes in both cell lines. In SH-SY5Y cells, CAW increased basal and maximal oxygen consumption without altering spare capacity, and attenuated A beta-induced decreases in mitochondrial respiration. CAW also prevented A beta-induced decreases in ATP and induced the expression of mitochondrial genes and proteins in both cell types. Caffeoylquinic acids from CAW were shown to have a similar effect on antioxidant and mitochondrial gene expression in neuroblastoma cells. Primary rat hippocampal neurons treated with CAW also showed an increase in mitochondrial and antioxidant gene expression.
Conclusions: These data suggest an effect of CAW on mitochondrial biogenesis, which in conjunction with activation of antioxidant response genes and normalizing calcium homeostasis, likely contributes to its neuroprotective action against A beta toxicity.

• 出版日期2015