[1]杨鹤年,张津铖,吴宿慧,等.生、熟地黄“生熟异用”功效差异的机制及质量标志物探析[J].西部中医药,2025,38(11):47-60.[doi:10.12174/j.issn.2096-9600.2025.11.09]
　YANG Henian,ZHANG Jincheng,WU Suhui,et al.Preliminary Study on the Mechanism of Efficacy Difference between Raw and Prepared Rhizoma Rehmanniae, and Quality Markers[J].Western Journal of Traditional Chinese Medicine,2025,38(11):47-60.[doi:10.12174/j.issn.2096-9600.2025.11.09]
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生、熟地黄“生熟异用”功效差异的机制及质量标志物探析()

《西部中医药》[ISSN:2096-9600/CN:62-1204/R]

卷:
38
期数:
2025年11期
页码:
47-60
栏目:
二次研究
出版日期:
2025-11-15

文章信息/Info

Title:
Preliminary Study on the Mechanism of Efficacy Difference between Raw and Prepared Rhizoma Rehmanniae, and Quality Markers
作者:
杨鹤年1, 张津铖2, 吴宿慧1,3, 李寒冰1,4, 李根林1,4
1.河南中医药大学药学院，河南 郑州 450046
2.北京中医药大学研究生院，北京 100105
3.河南省仲景方药健康衰老产业工程研究中心，河南 郑州 450046
4.河南中医药大学，河南 郑州 450046
Author(s):
YANG Henian1, ZHANG Jincheng2, WU Suhui1,3, LI Hanbing1,4, LI Genlin1,4
1.College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China
2.Graduate School, Beijing University of Chinese Medicine, Beijing 100105, China
3.Henan Engineering Research Center for Zhang Zhongjing Medical Heritage and Healthy Aging Industry, Zhengzhou 450046, China
4.Henan University of Chinese Medicine, Zhengzhou 450046, China
关键词:
生地黄; 熟地黄; 网络药理学; 生熟异用; 功效差异; 质量标志物
Keywords:
raw rhizoma rehmanniae; prepared rhizoma rehmanniae; network pharmacology; different uses of raw and processed herbs; efficacy difference; quality markers
分类号:
R285
DOI:
10.12174/j.issn.2096-9600.2025.11.09
文献标志码:
A
摘要:
目的探究生、熟地黄“生熟异用”功效差异的科学内涵及潜在质量标志物。 方法采用网络药理学方法，构建生、熟地黄炮制前后的“差异成分-靶点-通路”网络。通过文献检索筛选差异成分，利用Swiss Target Prediction预测潜在靶点；借助STRING数据库筛选最高置信度靶点，使用Cytoscape 3.7.2软件构建蛋白-蛋白互作网络，依据Degree值筛选关键靶点；通过Metascape数据库对核心靶点进行基因本体（gene ontology，GO）生物功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）信号通路富集分析；采用Autodock Vina平台开展分子对接，明确介导炮制前后药理作用差异的“核心成分-核心靶点-核心通路”及潜在功效差异质量标志物；结合中药质量标志物（Q-marker）“五原则”分析差异成分，预测炮制前后功效差异的关键Q-marker。 结果通过文献检索筛选出17种差异成分，预测获得299个潜在靶点，去重后得到96个靶点（含66个关键靶点）；富集分析得到4139个GO注释及334条KEGG通路，最终筛选出1个核心通路（神经活性配体-受体相互作用）、1个核心靶点［基质金属蛋白酶12（macrophage elastase 12，MMP12）］及4个核心糖类成分（棉子糖、甘露三糖、蔗糖、水苏糖），上述核心要素共同介导生、熟地黄功效差异；同时发现地黄多糖类成分为潜在功效差异质量标志物，结合Q-marker理论确定地黄苷D、毛蕊花糖苷、益母草苷、梓醇、地黄多糖、5-羟甲基糠醛、异麦角甾苷为地黄炮制前后功效差异的潜在Q-marker。 结论生、熟地黄通过“神经活性配体-受体相互作用”核心通路、MMP12核心靶点及棉子糖、甘露三糖、蔗糖、水苏糖4个核心糖类成分调控功效差异；地黄苷D、毛蕊花糖苷、益母草苷、梓醇、地黄多糖、5-羟甲基糠醛、异麦角甾苷可作为介导二者功效差异的质量标志物。
Abstract:
ObjectiveTo explore scientific connotation of efficacy difference between raw and prepared rhizoma rehmanniae, and potential quality markers. MethodsNetwork pharmacology was adopted to construct the network of "differential ingredients-targets-signaling pathways" for raw and processed rhizoma rehmanniae before and after processing. Differential components were screened out through literature retrieval, the potential targets were identified using Swiss Target Prediction; STRING database was applied to screen out the targets with highest confidence, Cytoscape 3.7.2 was adopted to construct protein-protein interaction network, and the key targets were screened in light of Degree values; Metascape data base was applied to conduct GO and KEGG signaling pathway enrichment analysis of the core targets; Autodock Vina platform was adopted to perform molecular docking, for the identification of "core ingredients-core targets-core pathways" that mediates pharmacological differences before and after processing, and potential efficacy-related quality markers; the differential components were analyzed based on "five-principle" of Q-marker for Traditional Chinese Medicine, and the key Q-markers of efficacy difference were predicted before and after processing. ResultsLiterature retrieval identified 17 differential ingredients, and yielded 299 potential targets after prediction, 96 targets were obtained after overlapping(containing 66 key targets); enrichment analysis yielded 4,139 GO annotations and 334 KEGG pathways, consequently to screen out one core pathway (neuroactive ligand-receptor interactions), one core target (MMP12) and four core polysaccharides including raffinose, levidulinose, saccharose and stachyose, and the above core elements jointly participated in the mediation of efficacy difference of raw and processed rhizoma rehmanniae; meanwhile, rehmanniae polysaccharides were the potential efficacy difference Q-markers. In light of Q-marker theory, rehmannioside D, verbascoside, leonuride, catalpol, rehmannia glutinosa polysaccharide, 5-hydroxyme-thylfurfural and isoverbascoside were the potential Q-markers of efficacy difference before and after processing. ConclusionRaw and prepared rhizoma rehmanniae could regulate efficacy difference via signaling pathway of "neuroactive ligand-receptor interactions", MMP12 core targets and four core polysaccharides including raffinose, levidulinose, saccharose and stachyose; rehmannioside D, verbascoside, leonuride, catalpol, rehmannia glutinosa polysaccharide, 5-hydroxymethylfurfural and isoverbascoside could be taken as the quality markers to mediate efficacy difference between the raw and processed ones.

备注/Memo

备注/Memo:
国家自然科学基金（81503363）；河南省科技厅科技研发专项资助项目（192102310173）。杨鹤年（1994—），男，硕士学位，助教。研究方向：中药药理学技术。
更新日期/Last Update: 2025-11-15