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Ergosta-7,9(11),22-trien-3β-ol alleviates intracerebral hemorrhage-induced brain injury and BV-2 microglial activation


Hsueh, P-J and Wang, M-H and Hsiao, C-K and Chen, C-K and Lin, F-L and Huang, S-H and Yen, J-L and Tsai, P-H and Kuo, Y-H and Hsiao, G, Ergosta-7,9(11),22-trien-3β-ol alleviates intracerebral hemorrhage-induced brain injury and BV-2 microglial activation, Molecules, 26, (10) pp. 1-18. ISSN 1420-3049 (2021) [Refereed Article]

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Copyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons 4.0 International (CC BY 4.0) license (

DOI: doi:10.3390/molecules26102970


Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized by an exacerbation of neuroinflammation and neuronal injury, for which few effective therapies are available at present. Inhibition of excessive neuroglial activation has been reported to alleviate ICH-related brain injuries. In the present study, the anti-ICH activity and microglial mechanism of ergosta-7,9(11),22-trien-3β-ol (EK100), a bioactive ingredient from Asian medicinal herb Antrodia camphorate, were evaluated. Post-treatment of EK100 significantly attenuated neurobehavioral deficit and MRI-related brain lesion in the mice model of collagenase-induced ICH. Additionally, EK100 alleviated the inducible expression of cyclooxygenase (COX)-2 and the activity of matrix metalloproteinase (MMP)-9 in the ipsilateral brain regions. Consistently, it was shown that EK100 concentration-dependently inhibited the expression of COX-2 protein in Toll-like receptor (TLR)-4 activator lipopolysaccharide (LPS)-activated microglial BV-2 and primary microglial cells. Furthermore, the production of microglial prostaglandin E2 and reactive oxygen species were attenuated by EK100. EK100 also attenuated the induction of astrocytic MMP-9 activation. Among several signaling pathways, EK100 significantly and concentration-dependently inhibited activation of c-Jun N-terminal kinase (JNK) MAPK in LPS-activated microglial BV-2 cells. Consistently, ipsilateral JNK activation was markedly inhibited by post-ICH-treated EK100 in vivo. In conclusion, EK100 exerted the inhibitory actions on microglial JNK activation, and attenuated brain COX-2 expression, MMP-9 activation, and brain injuries in the mice ICH model. Thus, EK100 may be proposed and employed as a potential therapeutic agent for ICH.

Item Details

Item Type:Refereed Article
Keywords:ergosta-7,9(11),22-trien-3β-ol, intracerebral hemorrhage, COX-2, MMP-9, microglia, JNK
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Lin, F-L (Dr Fan-Li Lin)
ID Code:146926
Year Published:2021
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-10-04
Last Modified:2021-11-18
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