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Pharmacological research

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Regulation of microglia inflammation and oligodendrocyte demyelination by Engeletin via the TLR4/RRP9/NF-κB pathway after spinal cord injury

Published:10 October 2024 DOI: 10.1016/j.phrs.2024.107448
Wang Chen , Leshu Zhang , Guangdi Zhong , Shuang Liu , Yuxuan Sun , Jiayun Zhang , Zehan Liu , Lichun Wang

Abstract

Microglia polarization is crucial for neuroinflammatory response after spinal cord injury (SCI). Small molecule compounds and hub genes play an important role in regulating microglia polarization, reducing neuroinflammatory response and oligodendrocyte demyelination after SCI. In this study, suitable data sets were used to screen hub genes, and Western blot and Immunofluorescence (IF) experiments were used to confirm the expressions of proteins related to SDAD1, RRP9 and NF-κB pathways under LPS/SCI conditions. Engeletin (ENG) reduced microglia polarization and inflammation in vivo and in vitro via the SDAD1, RRP9 or NF-κB signaling pathways. In addition, ENG binds to the membrane receptor Toll-like receptor 4 (TLR4) through small molecule-protein docking. COIP experiment and protein-protein docking revealed protein-protein interaction (PPI) between RRP9 and SDAD1. By gene knock-down (KD) / overexpression (OE) and Western blot experiments, RRP9 and SDAD1 can regulate inflammatory response through NF-κB signaling and ribosome biogenesis pathway. Western blot analysis showed that CU increased the expression of SDAD1, RRP9 and NF-κB pathway related proteins through TLR1/2, while C34 decreased the expression of SDAD1 and RRP9 proteins through TLR4. These results suggest that ENG can reduce inflammation through TLR4/RRP9(SDAD1)/NF-κB signaling pathway. In addition, we demonstrated that oligodendrocyte apoptosis and demyelination could be influenced by the regulation of microglia and tissue inflammation. In conclusion, this study found the gene Rrp9/Sdad1 and the small molecule compound ENG, which control the inflammatory response of microglia, and further explored the related mechanism of oligodendrocyte demyelination, which has important theoretical significance.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
(2R,3R)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2S,3R,4R,5S,6S)-3,4,5-trihydroxy-6-methyl-oxan-2-yl]oxy-chroman-4-one 572-31-6 C21H22O10 194 suppliers $22.00-$2890.00
(2R,3R)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2S,3R,4R,5S,6S)-3,4,5-trihydroxy-6-methyl-oxan-2-yl]oxy-chroman-4-one 572-31-6 C21H22O10 194 suppliers $22.00-$2890.00
(2R,3R)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2S,3R,4R,5S,6S)-3,4,5-trihydroxy-6-methyl-oxan-2-yl]oxy-chroman-4-one 572-31-6 C21H22O10 194 suppliers $22.00-$2890.00
(2R,3R)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3-[(2S,3R,4R,5S,6S)-3,4,5-trihydroxy-6-methyl-oxan-2-yl]oxy-chroman-4-one 572-31-6 C21H22O10 194 suppliers $22.00-$2890.00
CU-T12-9 1821387-73-8 C17H13F3N4O2 58 suppliers Inquiry
CU-T12-9 1821387-73-8 C17H13F3N4O2 58 suppliers Inquiry
CU-T12-9 1821387-73-8 C17H13F3N4O2 58 suppliers Inquiry
CU-T12-9 1821387-73-8 C17H13F3N4O2 58 suppliers Inquiry

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