Open AccessEthanol Extract of Elaeagnus glabra f. oxyphylla Branches Alleviates the Inflammatory Response Through Suppression of Cyclin D3/Cyclin-Dependent Kinase 11p58 Coupled to Lipopolysaccharide-Activated BV-2 Microglia
Author(s) -
HyeSun Lim,
Eunjin Sohn,
Yu Jin Kim,
Bu-Yeo Kim,
Joohwan Kim,
SooJin Jeong
Publication year - 2022
Publication title -
natural product communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.221
H-Index - 44
eISSN - 1934-578X
pISSN - 1555-9475
DOI - 10.1177/1934578x221075079
Subject(s) - tumor necrosis factor alpha , kinase , neuroinflammation , lipopolysaccharide , p38 mitogen activated protein kinases , microglia , chemistry , cyclin d1 , microbiology and biotechnology , protein kinase a , pharmacology , biology , inflammation , biochemistry , immunology , apoptosis , cell cycle
Neuroinflammation plays a pivotal role in the pathogenesis of neurodegenerative diseases and is characterized by microglial dysregulation. Here, we explored the beneficial effects of a leaf extract of Elaeagnus glabra f. oxyphylla (EGFO), a native medicinal plant to Korea, South China, Japan, and Taiwan, on neuroinflammation using lipopolysaccharide (LPS)-stimulated BV-2 microglia. Levels of the inflammatory mediators were determined by enzyme-linked immunosorbent assays and reverse transcription–polymerase chain reaction. The phospho levels of mitogen-activated protein kinases, which are key kinase molecules in the inflammatory signaling pathway in microglia, were analyzed by Western blotting. Treatment with EGFO significantly suppressed the LPS-mediated induction of nitric oxide and prostaglandin E 2 . Consistently, EGFO treatment in LPS-stimulated BV-2 cells markedly reduced the inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels. The best concentration of EGFO that could reduce TNF-α and IL-6 was 100 μg/mL. EGFO relatively reduced the messenger RNA expression of TNF-α and IL-6 by 0.36 and 0.32-fold ratio, respectively, compared to LPS treatment. Moreover, EGFO markedly reduced the phospho levels of p38 and the c-jun N-terminal kinase. Furthermore, antibody microarray and immunoblotting data revealed that the pharmacological mechanisms driving the antineuroinflammatory action of EGFO involve prevention of the cyclin D3/cyclin-dependent kinase 11 p58 (CDK11 p58 ) interaction. In conclusion, our results demonstrate that EGFO alleviates the inflammatory response through the suppression of cyclin D3/CDK11 p58 coupling in LPS-activated BV-2 microglia. We propose the potential of EGFO as a novel drug candidate for neurodegenerative diseases by targeting neuroinflammation.