Betulin isolated from Pyrola incarnata Fisch. inhibited lipopolysaccharide (LPS)-induced neuroinflammation with the guidance of computer-aided drug design.

Autor: Liu Q; Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironments, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China., Liu JP; Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironments, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China., Mei JH; Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironments, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China., Li SJ; Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironments, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China., Shi LQ; Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China., Lin ZH; CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China., Xie BY; Wuhan Institute for Drug and Medical Device Control, Wuhan 430075, China., Sun WG; Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China., Wang ZY; Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironments, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China., Yang XL; Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Infection, Immunology and Tumor Microenvironments, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China. Electronic address: yxlyxl117@163.com., Zou Y; Department of Pharmacy, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Institute of Pharmaceutical Innovation, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China. Electronic address: zouyu@wust.edu.cn., Fang W; Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China. Electronic address: wei.fang@nberc.com.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2020 Jun 15; Vol. 30 (12), pp. 127193. Date of Electronic Publication: 2020 Apr 13.
DOI: 10.1016/j.bmcl.2020.127193
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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