Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice

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.

Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

“…CAW dose-dependent effects on behavior were not modulated by pathology or gender. A treatment benefit of CAW (200 mg/kg/d for four weeks) in WT animals was previously reported both in male and female aged (20 month old) WT mice (as measured by Morris water maze, object location, and novel object recognition) [1,46]. This was recapitulated by CAW dose-dependent (200-1000 mg/kg/d for 3-4 weeks) cognitive benefits to both male and female 7-9 month old WT mice in the present study.…”

“…We have confirmed that these mechanisms also operate in aging wild-type (WT) mice [1]. In this study, we expand on our previous studies in female Tg2576 [13] and female 5XFAD mice [33] treated with 200 mg/kg/d CAW.…”

“…Centella asiatica (CA) has been utilized for its cognitive benefits for centuries in traditional Chinese and Ayurvedic medicine. Modern scientific studies in rodents [1][2][3] and in human subjects [4,5] have shown cognitive-enhancing or neurotropic properties of whole CA extracts, as well as some of its known active components [6]. These properties of CA may have relevance for the treatment of Alzheimer's disease (AD).…”

Centella asiaticaextract prevents visual impairment by promoting the production of rhodopsin in the retina

“…In addition, plant sterols and flavonoids are present in the whole extract, in addition to tannins, essential acids, phytosterols, mucilages, resins, free amino acids, flavonoids, alkaloids, bitter components, and fatty acids that are known to have no pharmacological activity [6]. Known preclinical efficacy includes pharmacological effects such as wound healing [7], venous strengthening [8], cognitive enhancement [9], antioxidant and DNA damage preventive properties [10], epilepsy prevention [11], antiinflammatory effects [12], and antidepressant properties [13]. Based on these findings, we investigated the protective effects of C. asiatica extract in model systems including human retinal pigment epithelial cells and experimental animals in which we induced oxidative stress and cytotoxicity.…”

The use of nootropics in Alzheimer’s disease: is there light at the end of the tunnel?

“…Increased in synaptic density and improvement in executive functions was also observed in healthy aged mice after treatment with CA 53 . Similarly, short treatment with CA has increased the expression of synaptic, mitochondrial, and antioxidant response genes and improved different domains of cognitive performance (executive function, memory, and learning) in 5xFAD animals as well as reduced the burden of Aβ plaque burden in the hippocampus 54 .…”