基于网络药理学的研究揭示了肉桂的抗寒及产热机制。

Network pharmacology-based research uncovers cold resistance and thermogenesis mechanism of Cinnamomum cassia.

作者信息

Jiang Xiao-Wen, Lu Hong-Yuan, Xu Zi-Hua, Zhang Ying-Shi, Zhao Qing-Chun

机构信息

Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, China.

Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, China.

出版信息

Fitoterapia. 2021 Mar;149:104824. doi: 10.1016/j.fitote.2020.104824. Epub 2020 Dec 31.

DOI:10.1016/j.fitote.2020.104824

PMID:33388379

Abstract

BACKGROUND

Cinnamomum cassia (L.) J.Presl (Cinnamon) was known as a kind of hot herb, improved circulation and warmed the body. However, the active components and mechanisms of dispelling cold remain unknown.

METHODS

The effects of several Chinses herbs on thermogenesis were evaluated on body temperature and activation of brown adipose tissue. After confirming the effect, the components of cinnamon were identified using HPLC-Q-TOF/MS and screened with databases. The targets of components were obtained with TCMSP, SymMap, Swiss and STITCH databases. Thermogenesis genes were predicted with DisGeNET and GeneCards databases. The protein-protein interaction network was constructed with Cytoscape 3.7.1 software. GO enrichment analysis was accomplished with STRING databases. KEGG pathway analysis was established with Omicshare tools. The top 20 targets for four compounds were obtained according to the number of edges of PPI network. In addition, the network results were verified with experimental research for the effects of extracts and major compounds.

RESULTS

Cinnamon extract significantly upregulated the body temperature during cold exposure.121 components were identified in HPLC-Q-TOF/MS. Among them, 60 compounds were included in the databases. 116 targets were obtained for the compounds, and 41 genes were related to thermogenesis. The network results revealed that 27 active ingredients and 39 target genes. Through the KEGG analysis, the top 3 pathways were PPAR signaling pathway, AMPK signaling pathway, thermogenesis pathway. The thermogenic protein PPARγ, UCP1 and PGC1-α was included in the critical targets of four major compounds. The three major compounds increased the lipid consumption and activated the brown adipocyte. They also upregulated the expression of UCP1, PGC1-α and pHSL, especially 2-methoxycinnamaldehyde was confirmed the effect for the first time. Furthermore, cinnamaldehyde and cinnamon extract activated the expression of TRPA1 on DRG cells.

CONCLUSION

The mechanisms of cinnamon on cold resistance were investigated with network pharmacology and experiment validation. This work provided research direction to support the traditional applications of thermogenesis.

摘要

背景

肉桂是一种性热的草药，能促进血液循环、温暖身体。然而，其散寒的活性成分及作用机制尚不清楚。

方法

通过观察体温及棕色脂肪组织的激活情况，评估几种中药对产热的影响。确认效果后，采用高效液相色谱-四极杆飞行时间串联质谱（HPLC-Q-TOF/MS）鉴定肉桂的成分，并利用数据库进行筛选。通过中药系统药理学数据库与分析平台（TCMSP）、SymMap、Swiss和STITCH数据库获取成分的作用靶点。利用DisGeNET和GeneCards数据库预测产热相关基因。使用Cytoscape 3.7.1软件构建蛋白质-蛋白质相互作用网络。通过STRING数据库进行基因本体（GO）富集分析。利用Omicshare工具进行京都基因与基因组百科全书（KEGG）通路分析。根据蛋白质-蛋白质相互作用网络的边数，获得四种化合物的前20个作用靶点。此外，通过提取物和主要化合物作用效果的实验研究对网络结果进行验证。

结果

肉桂提取物在冷暴露期间显著上调体温。通过HPLC-Q-TOF/MS鉴定出121种成分，其中60种化合物被纳入数据库。这些化合物共获得116个作用靶点，其中41个基因与产热相关。网络结果显示有27种活性成分和39个靶基因。通过KEGG分析，前3条通路为过氧化物酶体增殖物激活受体（PPAR）信号通路、腺苷酸活化蛋白激酶（AMPK）信号通路、产热通路。产热蛋白PPARγ、解偶联蛋白1（UCP1）和过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1-α）包含在四种主要化合物的关键作用靶点中。这三种主要化合物增加脂质消耗并激活棕色脂肪细胞。它们还上调UCP1、PGC1-α和激素敏感脂肪酶（pHSL）的表达，尤其是2-甲氧基肉桂醛的这种作用首次得到证实。此外，肉桂醛和肉桂提取物激活背根神经节（DRG）细胞上瞬时受体电位阳离子通道亚家族A成员1（TRPA1）的表达。