Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus

Abstract

Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.

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

“…The OLM is a hippocampal‐dependent test of location memory (Assini, Duzzioni, & Takahashi, ; Cipolotti, ) which is known to be impaired with aging in both humans and rodents (Arias‐Cavieres, Adasme, Sánchez, Muñoz, & Hidalgo, ; Sapkota, van der Linde, Lamichhane, Upadhyaya, & Pardhan, ; Wimmer, Hernandez, Blackwell, & Abel, ). The improvement in the OLM seen in this study is consistent with previous studies showing that asiatic acid, a major triterpene component of Centella asiatica (Siddiqui, Aslam, Ali, Khan, & Begum, ), improves performance in the same task in healthy as well as cognitively impaired rodents (Chaisawang et al., ; Sirichoat et al., ; Umka Welbat et al., ). It is also in line with reports that OLM performance by aged mice is improved by treatment with polyphenols (Carey, Gomes, & Shukitt‐Hale, ; Matsui et al., ), a class of compounds which both Centella asiatica in general (Siddiqui et al., ; Subban, Veerakumar, Manimaran, Hashim, & Balachandran, ) and CAW specifically are rich in (Gray, Zweig, Matthews, et al., ; Gray, Zweig, Murchison, et al., ; Soumyanath et al., ).…”

Hippocampal amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid GluA1 (AMPAGluA1) receptor subunit involves in learning and memory improvement following treatment withCentella asiaticaextract in adolescent rats

“…The graph shows the mean (±SEM) of escape latency in the reversal learning test. One way ANOVA showed no significant changes between the control and treatment animals (p > 0.05) with Cronbach's alpha: 1.000 reported health benefit of this herb is its improvement of brain function, particularly related to memory and learning, as the whole plant is very useful in improving these functions (Sari et al, 2014;Sirichoat et al, 2015;Yolanda et al, 2015). These benefits are due to the protective effect of the phytochemicals contained in the C. asiatica plant.…”

“…This plant has been widely used in Ayurvedic, African, and Chinese traditional medicine (Giribabu, Srinivasarao, Swapna Rekha, Muniandy, & Salleh, 2014;Vasavi et al, 2016). The best known beneficial effects of C. asiatica are its neuroprotective effect and its effects on cognitive function, particularly learning and memory (Doknark, Mingmalairak, Vattanajun, Tantisira, & Tantisira, 2014;Giribabu et al, 2014;Gray, Harris, Quinn, & Soumyanath, 2016;Gray et al, 2017;Sirichoat et al, 2015).…”

Molecular Targets Involved in the Neuroprotection Mediated by Terpenoids

“…Moreover, asiatic acid was able to enhance Notch1 and doublecortin (DCX) levels, which were strongly correlated with increased neurogenesis in the hypocampal dentante gyrus and, thus, a marked improvement in the spatial working memory in adult rats [114].…”