Betulin isolated from Pyrola incarnata Fisch. inhibited lipopolysaccharide (LPS)-induced neuroinflammation with the guidance of computer-aided drug design
| Autor: | Wei-Guang Sun, Qian Liu, Xiliang Yang, Zong-Hao Lin, Shuang-Jun Li, Li-Qiao Shi, Yu Zou, Zhen-Yu Wang, Jin-Ping Liu, Jia-Hui Mei, Wei Fang, Bai-Yan Xie |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Drug Lipopolysaccharide media_common.quotation_subject Clinical Biochemistry Molecular Conformation Nitric Oxide Synthase Type II Pharmaceutical Science Pharmacology Nitric Oxide 01 natural sciences Biochemistry Cell Line Proinflammatory cytokine Mice Structure-Activity Relationship chemistry.chemical_compound Griess test Drug Discovery Animals Pyrola Molecular Biology Neuroinflammation media_common Inflammation Betulin Dose-Response Relationship Drug 010405 organic chemistry Organic Chemistry Stereoisomerism Triterpenes 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry Drug Design Molecular Medicine Phosphorylation Pyrola incarnata Inflammation Mediators |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 30:127193 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2020.127193 |
| Popis: | 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 (1H-, 13C 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. |
| Databáze: | OpenAIRE |
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