Betulin isolated from Pyrola incarnata Fisch. inhibited lipopolysaccharide (LPS)-induced neuroinflammation with the guidance of computer-aided drug design. Issue 12 (15th June 2020)

• Record Type: Journal Article
• Authors: Liu, Qian; Liu, Jin-Ping; Mei, Jia-Hui; Li, Shuang-Jun; Shi, Li-Qiao; Lin, Zong-Hao; Xie, Bai-Yan; Sun, Wei-Guang; Wang, Zhen-Yu; Yang, Xi-Liang; Zou, Yu; Fang, Wei
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 12(2020)
• Publication Date: 2020-06-15
• Subjects: P. incarnata Pyrola incarnata -- LPS lipopolysaccharide -- NO nitricoxide -- TNF-α tumornecrosis factor alpha -- IL-6 interleukin-6 -- IL-1β interleukin-1 beta -- NF-κB p65 nuclear factor kappaB p65 -- IκB-α inhibitory κB-α -- JNKs c-Jun N-terminal kinases -- CNS central nervous system -- ELISA Enzyme-linked immunosorbent assay -- DAPI 4', 6-diamidino-2-phenylindole -- ANOVA one-way analysis of variance -- GPCRs G Protein-Coupled Receptors; Betulin -- Lipopolysaccharide -- Microglia cells -- Neuroinflammation -- Pyrola incarnata; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127193
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: Ten compounds including betulin were isolated from P. incarnata and elucidated. Betulin suppressed LPS-induced activation by inhibiting inflammatory cytokines. Molecular docking suggested possible anti-inflammatory mechanism of betulin. Betulin reduced iNOS expression, prevented JNKs and phosphorylation of NF-κB/p65. Abstract: This study aims to investigate active phytochemicals isolated from Pyrola incarnata Fisch. ( P. incarnata ) and their protection against neuroinflammation induced by LPS. Betulin, accompanied with other 9 compounds, were isolated from P. incarnata and elucidated by spectroscopic analysis ( 1 H-, 13 C NMR). ELISA kits and the measurement of NO production based on Griess reaction showed that betulin (5 ) (250 μg/mL) could suppress LPS-induced activation of microglial cell BV-2 better than others by inhibiting inflammatory cytokines (TNF-α, IL-6, IL-1β) expression and NO production. With the guidance of computer-aided drug design and the analysis of biological experiment, we demonstrated betulin could reduce LPS-induced iNOS expression, prevent JNKs pathways, and down-regulate the phosphorylation levels of NF-κB/p65. In conclusion, betulin isolated from P. incarnata possessed outstanding anti-neuroinflammation potential, presumably related to iNOS expression, JNKs and NF-κB/p65 pathways. Therefore, Pyrola incarnata may be a valuable natural resource and betulin is a potential drug for the treatment of neurodegenerative disorders by inhibiting inflammatory mediators.