Neuroprotective Effect of Asiatic Acid in Rat Model of Focal Embolic Stroke
- Authors
- Lee, Ki Yong; Bae, Ok-Nam; Weinstock, Shelley; Kassab, Mounzer; Majid, Arshad
- Issue Date
- 8월-2014
- Publisher
- PHARMACEUTICAL SOC JAPAN
- Keywords
- asiatic acid; tissue-plasminogen activator (t-PA); neuroprotection; rat embolic stroke model; stroke
- Citation
- BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.37, no.8, pp.1397 - 1401
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOLOGICAL & PHARMACEUTICAL BULLETIN
- Volume
- 37
- Number
- 8
- Start Page
- 1397
- End Page
- 1401
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/97860
- DOI
- 10.1248/bpb.b14-00055
- ISSN
- 0918-6158
- Abstract
- 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 3h 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 3h 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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Collections - College of Pharmacy > Department of Pharmaceutical Science > 1. Journal Articles
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