Abstract

Introduction Centella asiatica is a plant used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates age‐related spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its mechanism of improving age‐related cognitive impairment. This study investigates the effects of CAW on a variety of cognitive tasks as well as on synaptic density and mitochondrial and antioxidant pathways.MethodsTwenty‐month‐old CB6F1 mice were treated with CAW (2 mg/ml) in their drinking water for 2 weeks prior to behavioral testing. Learning, memory, and executive function were assessed using the novel object recognition task (NORT), object location memory task (OLM), and odor discrimination reversal learning (ODRL) test. Tissue was collected for Golgi analysis of spine density as well as assessment of mitochondrial, antioxidant, and synaptic proteins.ResultsCAW improved performance in all behavioral tests suggesting effects on hippocampal and cortical dependent memory as well as on prefrontal cortex mediated executive function. There was also an increase in synaptic density in the treated animals, which was accompanied by increased expression of the antioxidant response gene NRF2 as well as the mitochondrial marker porin.ConclusionsThese data show that CAW can increase synaptic density as well as antioxidant and mitochondrial proteins and improve multiple facets of age‐related cognitive impairment. Because mitochondrial dysfunction and oxidative stress also accompany cognitive impairment in many pathological conditions this suggests a broad therapeutic utility of CAW.

Highlights

  • Centella asiatica is a plant used for centuries to enhance memory

  • Our laboratory has previously reported that CAW improves performance in the Morris Water Maze (MWM) in mice exposed to Aβ as well as healthy older mice (Gray et al, 2016; Soumyanath et al, 2012)

  • We further explore the effects of CAW on age-­related cognitive impairment using a battery of behavioral tests assessing learning, memory, and executive function

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Summary

| INTRODUCTION

As the aging population in the United States continues to grow, so does the need for treating age-­related declines in health and cognitive function. The plant Centella asiatica (L) Urban, (Apiaceae), known in the United States as Gotu Kola, is used in traditional Chinese and Ayurvedic medicine to improve cognitive function (Kapoor, 1990; Shinomol, Muralidhara, & Bharath, 2011). A number of preclinical studies have demonstrated similar cognitive enhancing effects of Centella asiatica in multiple rodent models of pathological cognitive impairment (Gupta & Srivastava, 2003; Kumar & Gupta, 2002; Soumyanath et al, 2012; Veerendra Kumar & Gupta, 2003). Our laboratory has previously shown that a water extract of Centella asiatica (CAW) added to the drinking water can attenuate spatial memory impairments in healthy aged mice (Gray et al, 2016). We explore the effects of CAW on multiple cognitive domains beyond spatial memory, including recognition memory and executive function in healthy aged mice. We examine the effects of the extract on synaptic density as well as mitochondrial and antioxidant protein expression in the brains of treated animals

| MATERIALS AND METHODS
Findings
| DISCUSSION

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