Analyzing of the Composition and Medicinal Properties of Gastrodia elata during Cooking Based on Metabonomics and Network Pharmacology
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摘要: 目的：通过代谢组学、网络药理学及分子对接技术阐述天麻在熟制过程中成分及其药理活性变化。方法：使用LC-QTOF-MS及R语言对天麻成分进行检测和分析；通过PubChem数据库及文献查找筛选出具有生物活性的成分；使用Swiss target prediction数据库及SEA数据库对成分靶点进行预测，GeneCards数据库和OMIM数据库获取疾病靶点；通过STRING 11.5数据库及Cytoscape3.8.2软件绘制药物-化合物-靶点网络及靶点蛋白互作网络，筛选关键成分及靶点；通过DAVID数据库和OmicShare Tools对交集靶点进行GO富集和KEGG通路注释分析。结果：在熟制天麻和新鲜天麻中找出89种在含量方面具有差异的成分；分别筛选出11种具有治疗惊厥作用的成分以及410个潜在靶点，5种具有治疗糖尿病及其并发症作用的成分及698个潜在靶点；GO和KEGG富集分析发现天麻通过IL-17信号通路、cAMP信号通路、神经活性物质受体信号通路、阿尔茨海默病信号通路以及多巴胺能神经突触信号通路治疗惊厥，通过AGE-RAGE信号通路、HIF-1、VEGF以及TNF信号通路治疗糖尿病；分子对接结果显示筛选出的成分均结合在靶点蛋白的空腔中，结合自由能均小于0 kcal/mol，分子对接构象稳定。结论：熟制天麻具有更好的神经保护作用，新鲜天麻在治疗糖尿病及其引发的心血管疾病等方面具有更好的效果。Abstract: Objective: To explain the changes of composition and medicinal properties of Gastrodia elata during cooking by metabonomics, network pharmacology and molecular docking techniques. Methods: The components of Gastrodia elata were detected by LC-QTOF-MS and analyzed by R language. The bioactive ingredients were screened through PubChem database and literature. Swiss target prediction database and SEA database were used to predict the potential targets of the active ingredients, while GeneCards database and OMIM database were used to search for diseases-related targets. The STRING 11.5 database and Cytoscape3.8.2 software were used to construct drug-compound-target network and target protein interaction network. GO enrichment and KEGG pathway annotation analysis of intersection targets were performed by DAVID database and OmicShare Tools. Results: 89 Components with different contents were found in cooked Gastrodia elata and fresh Gastrodia elata. 11 Compounds were screened for the treatment of convulsion by 410 potential targets, and 5 compounds were screened for the treatment of diabetes and its complications by 698 potential targets. GO and KEGG enrichment analysis showed that Gastrodia elata treated convulsion through IL-17 signaling pathway, cAMP signaling pathway, neuroactive substance receptor signaling pathway, Alzheimer's disease signaling pathway and dopaminergic synaptic signaling pathway, while treated diabetes through AGE-RAGE signaling pathway, HIF-1, VEGF and TNF signaling pathway. The results of molecular docking showed that the selected components were all bound to the cavity of the target protein, and the binding free energy was less than 0 kcal/mol, and the molecular docking conformation was stable. Conclusion: Cooked Gastrodia elata has better neuroprotective effect, and fresh Gastrodia elata has better effect in treating diabetes mellitus and cardiovascular diseases.
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Key words:
- Gastrodia elata /
- cooking /
- metabonomics /
- network pharmacology /
- molecular docking
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图 1 熟制天麻及新鲜天麻差异成分的主成分分析（A）及热图（B）
Figure 1. Principal component analysis (A) and heat map (B) of different components of cooked and fresh Gastrodia elata
图 2 差异成分靶点与疾病靶点的韦恩图及网络图
Figure 2. Venn diagram and network diagram of differential component targets and disease targets
注：A、C为熟制天麻，B、D为新鲜天麻。
图 4 天麻成分干预惊厥及糖尿病基因GO富集及KEGG富集分析结果
Figure 4. Analysis results of GO enrichment and KEGG enrichment of genes affected by Gastrodia elata components in convulsion and diabetes
注：A、B为熟制天麻干预惊厥靶点基因进行富集分析结果；C、 D为新鲜天麻干预糖尿病靶点基因进行富集分析结果。
表 1 熟制天麻及新鲜天麻的成分及功能
Table 1. Ingredients and functions of cooked and fresh Gastrodia elata
化合物 PubChem ID 成分 分子式 功能 熟制天麻 4-Hydroxybenzaldehyde 126 4-羟基苯甲醛 C7H6O2 降血糖[20]，抗氧化[21]，
抗惊厥与癫痫[22]Daidzein 5281708 大豆黄酮 C15H10O4 抗肿瘤[23]，抗健忘[24]，治疗2型糖尿病[25]，降血压[26] Nicotinamide 936 烟酰胺 C6H6N2O 保护神经元[27]，抗惊厥[28]治疗1型糖尿病[29]，缓解胰岛素抵抗[30] p-Coumaric Acid 637542 p-香豆酸 C9H8O3 神经保护作用[31]，抗癌[32-33]，修复肝损伤[34]，调节免疫及抗炎活性[35] Bavachinin 10337211 补骨脂二氢黄酮甲醚 C21H22O4 治疗哮喘[36]，抗肿瘤[37-38] Cordycepin 6303 虫草素 C10H13N5O3 神经保护作用[39-40]，治疗哮喘[41] Gastrodin 115067 天麻素 C13H18O7 抗健忘[42]，促进记忆[43]，神经保护作用[44-45]，保肝护肝[46] Isoferulic acid 736186 异阿魏酸 C10H10O4 抗健忘[47] Biotin 171548 生物素 C10H16N2O3S 治疗脑损伤及记忆障碍[48]，治疗糖尿病[49] Peonidin-3-O-glucoside 14311151 芍药苷-3-O-葡萄糖苷 C22H23O11+ 降血糖血脂[50]，抗氧化[51] Luteolin-7-O-glucoside 5280637 木犀草素-7-O-葡萄糖苷 C21H20O11 调节免疫[52]，抗炎[53] 新鲜天麻 Agmatine 199 精胺 C5H14N4 治疗脑梗塞及认知障碍[54]，缓解疼痛[55] Spermidine 1102 亚精胺 C7H19N3 抗癌[56]，治疗心血管疾病[57] Ferulic acid 445858 阿魏酸 C10H10O4 抗氧化[58]，抗炎[59] Ononin 442813 芒柄花素-7-O-葡萄糖苷 C22H22O9 抗氧化[60]，抗炎[61] Nicotinic acid 938 烟酸 C6H5NO2 治疗心血管疾病[62] 
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