# Mechanisms underlying the cognitive effects of Centella asiatica water extract and constituent compounds in the 5xFAD mouse model of Alzheimer's Disease

> **NIH NIH U19** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $43,432

## Abstract

Project Summary/Abstract
Oxidative stress, mitochondrial dysfunction and neuroinflammation are inter-related processes central to the
pathogenesis and progression of Alzheimer's disease (AD). Mitochondrial dysfunction increases levels of
reactive oxygen species (ROS), and together these increase pro-inflammatory cytokines. Pro-inflammatory
cytokines, along with the increased ROS, cause further damage to mitochondria perpetuating a destructive
cycle that contributes to cell death and cognitive decline. This underlying biology suggests that a multi-targeted
agent could be an effective treatment strategy for AD. The traditional use of Centella asiatica herb to improve
cognitive function is supported by a substantial body of preclinical literature. We have shown that a water
extract of Centella asiatica (CAW) enhances synaptic density, activates the antioxidant response pathway and
improves mitochondrial deficits in isolated neurons as well as in mouse models of aging and AD, in which CAW
also improved cognitive performance. Our in vitro preliminary data also suggest anti-inflammatory effects of
CAW; however, this remains to be confirmed in vivo. The 5xFAD mouse model of Aβ accumulation shows
elevated neuroinflammation compared to wild type (WT) mice. This project will examine changes in markers of
neuroinflammation in stored brains from male and female 5xFAD mice whose cognition improved following
treatment with CAW in their drinking water. We have also found also triterpenes (TTs) and caffeoylquinic acids
(CQAs) present in CAW affect antioxidant, mitochondrial and synaptic health in vitro and can improve cognition
in 5xFAD mice. However, the specific associations of these compounds with the neuroprotective activities of
CAW remain to be elucidated. Using additional stored brain samples, we will investigate the effects CAW or
equivalent amounts of TTs and CQAs mixed in the diet, on markers of antioxidant response, mitochondrial
activity, synaptic density, neuroinflammation and Aβ pathology in male and female 5xFAD mice. We will
measure CQA and TT levels in the plasma following each treatment, both to corelate to their biological effects
and to explore reasons for the differential behavioral response seen when CAW was administered in the
drinking water versus in the diet. This project will inform future clinical trials of CAW by evaluating the role of
neuroinflammatory markers as biological signatures of target engagement by CA, the validity of using TT and
CQA as chemical markers to standardize CAW preparations, and the optimum mode of administration of CAW.
This work complements the parent grant investigating resilience promoting effects of CAW, CQAs and TTs in
healthy aged mice, where oxidative stress, declining mitochondrial function and neuroinflammation may occur.

## Key facts

- **NIH application ID:** 10285483
- **Project number:** 3U19AT010829-01S1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Amala Soumyanath
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $43,432
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285483

## Citation

> US National Institutes of Health, RePORTER application 10285483, Mechanisms underlying the cognitive effects of Centella asiatica water extract and constituent compounds in the 5xFAD mouse model of Alzheimer's Disease (3U19AT010829-01S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10285483. Licensed CC0.

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