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

文献类型： 外文期刊

作者： Liu, Qian 1 ; Liu, Jin-Ping 1 ; Mei, Jia-Hui 1 ; Li, Shuang-Jun 1 ; Shi, Li-Qiao 2 ; Lin, Zong-Hao 3 ; Xie, Bai-Yan 4 ; S 1 ;

作者机构： 1.Wuhan Univ Sci & Technol, Med Coll, Inst Infect Immunol & Tumor Microenvironm, Dept Pharm,Hubei Prov Key Lab Occupat Hazard Iden, Wuhan 430081, Peoples R China

2.Hubei Acad Agr Sci, Hubei Biopesticide Engn Res Ctr, 8 Nanhu Ave, Wuhan 430064, Peoples R China

3.Chinese Acad Sci, South China Sea Inst Oceanol, CAS Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, Guangzhou 510301, Peoples R China

4.Wuhan Inst Drug & Med Device Control, Wuhan 430075, Peoples R China

5.Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Pharm, Hubei Key Lab Nat Med Chem & Resource Evaluat, Wuhan 430030, Peoples R China

6.Wuhan Univ Sci & Technol, Inst Pharmaceut Innovat, Dept Pharm,Med Coll, Hubei Prov Key Lab Occupat Hazard Identificat & C, Wuhan 430081, Peoples R China

关键词： Betulin; Lipopolysaccharide; Microglia cells; Neuroinflammation; Pyrola incarnata

期刊名称：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS （ 影响因子：2.823； 五年影响因子：2.677 ）

ISSN： 0960-894X

年卷期： 2020 年 30 卷 12 期

页码：

收录情况： SCI

摘要： 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 (H-1-, C-13 NMR). ELISA kits and the measurement of NO production based on Griess reaction showed that betulin (5) (250 mu g/mL) could suppress LPS-induced activation of microglial cell BV-2 better than others by inhibiting inflammatory cytokines (TNF-alpha, IL-6, IL-1 beta) 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-kappa B/p65. In conclusion, betulin isolated from P. incarnata possessed outstanding anti-neuroinflammation potential, presumably related to iNOS expression, JNKs and NF-kappa B/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.

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