Ergosta-7,9(11),22-trien-3β-ol Alleviates Intracerebral Hemorrhage-Induced Brain Injury and BV-2 Microglial Activation

Autor: Mong Heng Wang, Shu Hsien Huang, Jing Lun Yen, Fan Li Lin, Chih Kuang Chen, Ping Huei Tsai, Po Jen Hsueh, Che Jen Hsiao, Yueh-Hsiung Kuo, George Hsiao
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
MAPK/ERK pathway
Lipopolysaccharide
Pharmaceutical Science
microglia
Organic chemistry
Pharmacology
Analytical Chemistry
Mice
chemistry.chemical_compound
0302 clinical medicine
QD241-441
Ergosterol
Drug Discovery
Prostaglandin E2
0303 health sciences
biology
Microglia
Brain
medicine.anatomical_structure
Matrix Metalloproteinase 9
Chemistry (miscellaneous)
Molecular Medicine
Signal transduction
MMP-9
Signal Transduction
medicine.drug
MAP Kinase Signaling System
Article
03 medical and health sciences
medicine
Animals
Physical and Theoretical Chemistry
Neuroinflammation
Cerebral Hemorrhage
030304 developmental biology
Intracerebral hemorrhage
Macrophages
JNK Mitogen-Activated Protein Kinases
Macrophage Activation
COX-2
medicine.disease
intracerebral hemorrhage
Mice
Inbred C57BL
chemistry
Cyclooxygenase 2
Brain Injuries
biology.protein
Cyclooxygenase
ergosta-7
9(11)
22-trien-3β-ol
JNK
Polyporales
030217 neurology & neurosurgery
Zdroj: Molecules, Vol 26, Iss 2970, p 2970 (2021)
Molecules
Volume 26
Issue 10
ISSN: 1420-3049
Popis: 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.
Databáze: OpenAIRE
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