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

Po Jen Hsueh, Mong Heng Wang, Che Jen Hsiao, Chih Kuang Chen, Fan Li Lin, Shu Hsien Huang, Jing Lun Yen, Ping Huei Tsai, Yueh Hsiung Kuo, George Hsiao

Research output: Contribution to journalArticlepeer-review

Abstract

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 Antro-dia 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. Further-more, 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.

Original languageEnglish (US)
Article number2970
JournalMolecules
Volume26
Issue number10
DOIs
StatePublished - May 2 2021

Keywords

  • COX-2
  • Ergosta-7,9(11),22-trien-3β-ol
  • Intracerebral hemorrhage
  • JNK
  • MMP-9
  • Microglia

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Ergosta-7,9(11),22-trien-3β-ol alleviates intracerebral hemorrhage-induced brain injury and bv-2 microglial activation'. Together they form a unique fingerprint.

Cite this