Centella asiatica is a medicinal plant used to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates β-amyloid (Aβ)-induced spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its in vivo mechanism of improving Aβ-related cognitive impairment. This study investigates the effects of CAW on learning, memory and executive function as well as mitochondrial function and antioxidant response in the 5xFAD model of Aβ accumulation.

Seven month old 5xFAD female mice were treated with CAW (2 mg/mL) in their drinking water for two weeks prior to behavioral testing. Learning, memory and executive function were assessed using the object location memory task (OLM), conditioned fear response (CFR) and odor discrimination reversal learning (ODRL) test. Mitochondrial function was profiled using the Seahorse XF platform in hippocampal mitochondria isolated from these animals and tissue was harvested for assessment of mitochondrial, antioxidant and synaptic proteins.

CAW improved performance in all behavioral tests in the 5xFAD but had no effect on WT animals. Hippocampal mitochondrial function was improved and hippocampal and cortical expression of mitochondrial genes was increased in CAW-treated 5xFAD mice. Gene expression of the transcription factor NRF2, as well as its antioxidant target enzymes, was also increased with CAW treatment in both WT and 5xFAD mice. CAW treatment also decreased Aβ-plaque burden in the hippocampus of treated 5xFAD mice but had no effect on plaques in the cortex.

These data show that CAW can improve many facets of Aβ-related cognitive impairment in 5xFAD mice. Oral treatment with CAW also attenuates hippocampal mitochondrial dysfunction in these animals. Because mitochondrial dysfunction and oxidative stress accompany cognitive impairment in many pathological conditions beyond Alzheimer's disease, this suggests potentially broad therapeutic utility of CAW.

积雪草是用于增强记忆力的药用植物。我们以前已经表明，积雪草（CAW）的水提取物可减轻β-淀粉样蛋白（Aβ）诱导的小鼠空间记忆不足，并改善神经元健康。然而，CAW对其他认知领域的作用及其改善Aβ相关认知障碍的体内机制尚待探索。这项研究调查了CAW对Aβ积累的5xFAD模型中学习，记忆和执行功能以及线粒体功能和抗氧化反应的影响。

在行为测试之前，对七个月大的5xFAD雌性小鼠在其饮用水中用CAW（2 mg / mL）处理了两周。使用对象位置记忆任务（OLM），条件恐惧反应（CFR）和气味识别逆向学习（ODRL）测试评估学习，记忆和执行功能。使用Seahorse XF平台分析从这些动物分离的海马线粒体中的线粒体功能，并收集组织以评估线粒体，抗氧化剂和突触蛋白。

在5xFAD中，CAW在所有行为测试中均改善了性能，但对野生动物没有影响。在CAW处理的5xFAD小鼠中，海马线粒体功能得到改善，海马和线粒体基因的皮质表达增加。在野生型和5xFAD小鼠中，通过CAW处理，转录因子NRF2的基因表达及其抗氧化剂靶酶也增加了。CAW处理还可以降低经治疗的5xFAD小鼠海马的Aβ斑块负担，但对皮质斑块没有影响。

这些数据表明，CAW可以改善5xFAD小鼠Aβ相关认知障碍的许多方面。用CAW口服治疗还可以减轻这些动物的海马线粒体功能障碍。由于线粒体功能障碍和氧化应激伴随着除阿尔茨海默氏病之外的许多病理状况中的认知障碍，因此，这提示了CAW的潜在治疗用途。