Neuroprotective effect of asiatic acid in rat model of focal embolic stroke
Open accessAbstract
Asiatic acid (AA) is a pleiotropic neuroprotective agent that has been shown to attenuate infarct volume in mouse and rat models of focal ischemia and has a long clinically relevant therapeutic time-window. Because in a future trial AA would be administered with tissue-plasminogen activator (t-PA), the only approved acute stroke therapy, we sought to determine the effect of AA when co-administered with t-PA in a rat focal embolic stroke model. Male rats were treated with AA (75 mg/kg) alone, low-dose t-PA (2.5 mg/kg) alone, or a combination of AA and low-dose t-PA at 3 h after inducing embolic stroke. AA significantly reduced infarct volume whereas low-dose t-PA alone did not reduce infarct volume compared with vehicle. Significantly, combination treatment further enhanced reduction of infarct volume versus AA alone. Treatment with AA reduced cytochrome c (CytoC) and apoptosis-inducing factor (AIF) release from brain mitochondria after ischemia. AA was also neuroprotective against L-glutamate-induced toxicity in primary cortical neurons. In summary, combination treatment with AA and low-dose t-PA at 3 h after embolic stroke reduces infarct volume, improves neurological outcome, and provides neuroprotection. The neuroprotective effects of AA were partially associated with reduction of AIF and CytoC release.
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In vitro studies show CAW whole extract and isolated compounds facilitate neurite outgrowth and elicit neuroprotection.
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From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [111]
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- Authors
- Lee, K. Y., Bae, O.-N., Weinstock, S., Kassab, M., & Majid, A.
- Affiliations
- Korea University (KR)
- Hanyang University (KR)
- ZYMES, LLC
- Michigan State University (US)
- Venue
- Biological and Pharmaceutical Bulletin
- Publisher
- Pharmaceutical Society of Japan
- Published
- 2014
- Volume
- 37
- Issue
- 8
- Pages
- 1397-1401
- ISSN
- 0918-6158 (ISSN-L)
- 1347-5215
- OpenAlex
- W2085392936
- Cited by
- 31
- References
- 25
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 1
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Biological and Pharmaceutical Bulletin (publishedVersion)
- PubMed (publishedVersion)
- The Royal Society of Chemistry’s Journals, Books and Databases (The Royal Society of Chemistry) (submittedVersion)
- Funders
- National Research Foundation
- National Research Foundation of Korea
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- asiatic acid, neuroprotection, embolic stroke, focal cerebral ischemia, tissue plasminogen activator, combination therapy, infarct size, apoptosis-inducing factor, cytochrome c release, mitochondrial apoptosis, cortical neurons, neurological outcome
- MeSH terms
- Animals, Disease Models, Animal, Male, Mitochondria, Neurons, Rats, Sprague-Dawley, Rats, Wistar, Neuroprotective Agents, Infarction, Middle Cerebral Artery, Cytochromes c, Apoptosis Inducing Factor, Pentacyclic Triterpenes
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