Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid overexpressing mice
Open accessAbstract
Centella asiatica is a medicinal plant used to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates β-amyloid (Aβ)-induced spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its in vivo mechanism of improving Aβ-related cognitive impairment. This study investigates the effects of CAW on learning, memory and executive function as well as mitochondrial function and antioxidant response in the 5xFAD model of Aβ accumulation. Seven month old 5xFAD female mice were treated with CAW (2 mg/mL) in their drinking water for two weeks prior to behavioral testing. Learning, memory and executive function were assessed using the object location memory task (OLM), conditioned fear response (CFR) and odor discrimination reversal learning (ODRL) test. Mitochondrial function was profiled using the Seahorse XF platform in hippocampal mitochondria isolated from these animals and tissue was harvested for assessment of mitochondrial, antioxidant and synaptic proteins. CAW improved performance in all behavioral tests in the 5xFAD but had no effect on WT animals. Hippocampal mitochondrial function was improved and hippocampal and cortical expression of mitochondrial genes was increased in CAW-treated 5xFAD mice. Gene expression of the transcription factor NRF2, as well as its antioxidant target enzymes, was also increased with CAW treatment in both WT and 5xFAD mice. CAW treatment also decreased Aβ-plaque burden in the hippocampus of treated 5xFAD mice but had no effect on plaques in the cortex. These data show that CAW can improve many facets of Aβ-related cognitive impairment in 5xFAD mice. Oral treatment with CAW also attenuates hippocampal mitochondrial dysfunction in these animals. Because mitochondrial dysfunction and oxidative stress accompany cognitive impairment in many pathological conditions beyond Alzheimer's disease, this suggests potentially broad therapeutic utility of CAW.
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Centella asiatica is a potential anti-Alzheimer's herbal drug.
“Research reports have proven CA to be a potential anti-AD herbal drug.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [106]
Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid-overexpressing mice.
“In a preclinical animal model, CA was reported to attenuate hippocampal mitochondrial dysfunction and improve memory and executive function in β-amyloid-overexpressing mice [106].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [106]
Activation of Nrf2 by Centella asiatica extracts improved mitochondrial and cognitive function and enhanced synaptic density in Alzheimer's disease and aging mouse models.
“Another Nrf2 activating compound is Centella asiatica extracts, which can activate Nrf2 in neuroblastoma cells, isolated primary neurons and in the brains of AD and aging mouse models. This activation improved mitochondrial and cognitive function, and enhanced synaptic density [113,114,115].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [114]
In previous experiments, CAW treatment reduced Aβ plaques in 5XFAD hippocampus when higher baseline Aβ burden (>3%) was present.
“However, in our previous experiments, CAW treatment has been seen to reduce Aβ plaques in 5XFAD hippocampus [33] where a higher baseline Aβ burden (> 3%) was present.”
From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [33]
Previous lab work showed Nrf2 expression is elevated further with CAW treatment in seven month old 5XFAD female mice.
“Our laboratory has shown Nrf2 expression, specifically, is elevated further with CAW treatment in seven month old 5XFAD female mice [33], an observation shown in the present study to occur in a CAW dose-dependent manner.”
From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [33]
Previous studies observed increased hippocampal and cortical mitochondrial gene expression and increased mitochondrial activity in response to CAW treatment.
“We have previously observed increased hippocampal and cortical mitochondrial gene expression [46] and increased mitochondrial activity [33] in response to CAW treatment.”
From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [33]
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- Authors
- Gray, N. E., Zweig, J. A., Caruso, M., Zhu, J. Y., Wright, K. M., Quinn, J. F., & Soumyanath, A.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- Gray, Nora E.
- ORCID
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 93
- Pages
- 1-9
- ISSN
- 1044-7431 (ISSN-L)
- PMC
- PMC6242741
- OpenAlex
- W2894301429
- Cited by
- 85
- References
- 72
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 17 · 2023: 8 · 2022: 7 · 2021: 13 · 2020: 14 · 2019: 9
- FWCI
- 12.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular and Cellular Neuroscience (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH-NCCIH (R00AT008831, R01AT008099, T32 AT002688)
- Department of Veterans Affairs
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Centella asiatica, amyloid-beta, 5xFAD mice, executive function, memory, learning, Nrf2, oxidative stress, antioxidant response, amyloid plaques, Alzheimer's disease, medicinal plant extracts, object location memory, conditioned fear response
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Hippocampus, Learning, Memory, Mice, Transgenic, Mitochondria, Neurons, Plant Extracts, Triterpenes, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Centella, Executive Function
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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