Centella asiatica Attenuates Mitochondrial Dysfunction and Oxidative Stress in Aβ-Exposed Hippocampal Neurons.

Nora E Gray,Amala Soumyanath,Joseph F Quinn,Maya Caruso,Jonathan A Zweig,Donald G Matthews

doi:10.1155/2017/7023091

Abstract

Centella asiatica has been used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) protects against the deleterious effects of amyloid-β (Aβ) in neuroblastoma cells and attenuates Aβ-induced cognitive deficits in mice. Yet, the neuroprotective mechanism of CAW has yet to be thoroughly explored in neurons from these animals. This study investigates the effects of CAW on neuronal metabolism and oxidative stress in isolated Aβ-expressing neurons. Hippocampal neurons from amyloid precursor protein overexpressing Tg2576 mice and wild-type (WT) littermates were treated with CAW. In both genotypes, CAW increased the expression of antioxidant response genes which attenuated the Aβ-induced elevations in reactive oxygen species (ROS) and lipid peroxidation in Tg2576 neurons. CAW also improved mitochondrial function in both genotypes and increased the expression of electron transport chain enzymes and mitochondrial labeling, suggesting an increase in mitochondrial content. These data show that CAW protects against mitochondrial dysfunction and oxidative stress in Aβ-exposed hippocampal neurons which could contribute to the beneficial effects of the extract observed in vivo. Since CAW also improved mitochondrial function in the absence of Aβ, these results suggest a broader utility for other conditions where neuronal mitochondrial dysfunction occurs.

Highlights

Alzheimer’s disease (AD) is the most common form dementia affecting an estimated 5.4 million people in the United States alone [1]
Dried Centella asiatica was purchased (Oregon’s Wild Harvest, GOT03193c-OHQ01), and its identity was confirmed by comparing its thin layer chromatographic profile with that reported in the literature [23] and the Centella asiatica samples used in our previous studies [18]
We found that after seven days in culture, Tg2576 neurons showed a significant increase in intracellular reactive oxygen species (ROS) relative to WT neurons (Figure 1(a))

Summary

Introduction

Alzheimer’s disease (AD) is the most common form dementia affecting an estimated 5.4 million people in the United States alone [1]. Despite continued increase in the prevalence of AD, effective therapies remain limited owing, at least in part, to an incomplete understanding of the underlying biology of the disease. In AD patients, the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles is accompanied by synaptic dysfunction, cell death, and severe cognitive impairment [2, 3]. Increased oxidative stress is likewise considered to be an early event in the brains of AD patients [9, 10]. These abnormalities have been observed in many in vitro and in vivo AD model systems as well [11,12,13]

Objectives

Methods

Results

Conclusion