# Triterpene and Caffeoylquinic Acid Constituents Contribute to the Cognitive-Enhancing, but Not Anxiolytic, Effects of a Water Extract of Centella asiatica in Aged Mice

## TL;DR

A water extract of Centella asiatica improves learning and cognitive flexibility in aged mice, but these effects are likely due to specific compounds like triterpene and caffeoylquinic acid, not anxiolytic effects.

## Contribution

This study identifies triterpene and caffeoylquinic acid as key contributors to the cognitive benefits of Centella asiatica extract in aged mice.

## Key findings

- Triterpene and caffeoylquinic acid improved learning in aged mice of both sexes.
- Triterpene alone enhanced cognitive flexibility in aged mice of both sexes.
- No anxiolytic effects were observed with any treatment.

## Abstract

Background/objectives: A water extract of the plant Centella asiatica (CAW) has been shown to improve cognitive deficits in aged mice when administered for 5 weeks in drinking water. However, the contribution of the constituent compounds within CAW to the beneficial effects of the extract remains unelucidated. This study evaluated the effects of triterpene (TT) and caffeoylquinic acids (CQA) found within CAW, on learning, cognitive flexibility, memory, and anxiety-like behaviors in aged C57BL6 mice. Methods: Eighteen-month-old male and female C57BL6 mice were administered either TT, CQA, or the combination (TT+CQA) in their drinking water for a total of 5 weeks, at concentrations corresponding to their presence in CAW. During the final two weeks of treatment learning, executive function, memory, and anxiety were assessed. Results: Aged mice of both sexes showed significant improvement in learning when treated with TT and CQA separately and in combination. Treatment with TT also improved cognitive flexibility in aged mice of both sexes, but CQA and the combination of TT+CQA did not alter cognitive flexibility in aged male mice. There was no effect on recognition memory or anxiety in any of the treatment groups (TT, CQA, TT+CQA) relative to mice treated with the vehicle control although there was a trend towards improved recognition memory with TT treatment. Conclusions: These results suggest that the TT and CQA present in CAW likely contribute to its previously reported amelioration of age-related cognitive changes, especially in learning and cognitive flexibility, while other constituents may be responsible for CAW’s anxiolytic effects.