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Abstract

Intracerebral hemorrhage (ICH) is a devastating neurological disorder characterized byan exacerbation of neuroinflammation and neuronal injury, for which few effective therapies areavailable at present. Inhibition of excessive neuroglial activation has been reported to alleviateICH-related brain injuries. In the present study, the anti-ICH activity and microglial mechanismof 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 neurobehavioraldeficit 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 matrixmetalloproteinase (MMP)-9 in the ipsilateral brain regions. Consistently, it was shown that EK100concentration-dependently inhibited the expression of COX-2 protein in Toll-like receptor (TLR)-4activator lipopolysaccharide (LPS)-activated microglial BV-2 and primary microglial cells. Furthermore, the production of microglial prostaglandin E2 and reactive oxygen species were attenuatedby EK100. EK100 also attenuated the induction of astrocytic MMP-9 activation. Among severalsignaling pathways, EK100 significantly and concentration-dependently inhibited activation of c-JunN-terminal kinase (JNK) MAPK in LPS-activated microglial BV-2 cells. Consistently, ipsilateral JNKactivation was markedly inhibited by post-ICH-treated EK100 in vivo. In conclusion, EK100 exertedthe inhibitory actions on microglial JNK activation, and attenuated brain COX-2 expression, MMP-9activation, and brain injuries in the mice ICH model. Thus, EK100 may be proposed and employedas a potential therapeutic agent for ICH.

Item Type:	Article
Authors/Creators:	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
Keywords:	ergosta-7,9(11),22-trien-3β-ol, intracerebral hemorrhage, COX-2, MMP-9, microglia, JNK
Journal or Publication Title:	Molecules
Publisher:	Molecular Diversity Preservation International
ISSN:	1420-3049
DOI / ID Number:	10.3390/molecules26102970
Copyright Information:	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 (https://creativecommons.org/licenses/by/4.0/).
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