基于指纹图谱和网络药理学的经典名方三化汤质量标志物预测

目的：建立三化汤的指纹图谱，利用网络药理学方法筛选质量控制指标性成分。方法：建立15批三化汤的高效液相色谱法（HPLC）指纹图谱，采用“中药色谱指纹图谱相似度评价系统”（2012A版）进行相似度评价后确定共有峰；通过与对照药材、对照品比对，对峰进行归属和指认；并采用正交偏最小二乘法-判别分析（OPLS-DA）对15批三化汤进行质量评价；利用网络药理学筛选三化汤的核心作用靶点和通路，通过分子对接将核心靶点与13个成分进行对接验证，筛选出三化汤质量控制的指标性成分。结果：三化汤物质基准的HPLC指纹图谱共标定17个共有峰，相似度均大于0.97；共指认13个色谱峰，分别为辛弗林、柚皮苷、橙皮苷、新橙皮苷、芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚、厚朴酚、和厚朴酚、紫花前胡苷、异欧前胡素，其中含量排名前4的成分为柚皮苷、新橙皮苷、辛弗林、紫花前胡苷；OPLS-DA将样品分为3类，通过变量重要性投影得出新橙皮苷、柚皮苷、紫花前胡苷、大黄酸对三化汤物质基准影响较大；网络药理学预测13个成分可能通过肿瘤蛋白P53 (TP53)、蛋白激酶B1 (Akt1)、90 kDa热休克蛋白αA1 (HSP...

Prediction of Quality Markers of Classical Formula Sanhua Tang Based on Fingerprint and Network Pharmacology

Objective To establish the fingerprints of Sanhua Tang and screen the quality control index ingredients by using the network pharmacology method.Methods First, the HPLC fingerprints of 15 batches of Sanhua Tang were established, and the common peaks were identified after the similarity evaluation using the Chinese Medicine Chromatographic Fingerprints Similarity Evaluation System (version 2012A); then, the peaks were attributed and identified by comparing with the control herbs and the control products, and the quality evaluation of the 15 batches of Sanhua Tang was carried out by using the OPLS-DA method. Secondly, the core targets and pathways of Sanhua Tang were screened by using the network pharmacology method. Finally, the core targets were verified by molecular docking with 13 components, and the index components of Sanhua Tang were screened for quality control.Results The HPLC fingerprints of the benchmarking of Sanhua Tang substances identified 17 common peaks with similarity greater than 0.97, and 13 chromatographic peaks were recognized, such as aloe-emodin, rhein, emodin, physcioner, chrysophanol, naringin, neohesperidin, hesperidin, synephrine, magnolol, honokiol, isoimperatorin, and nodakenin. Among them, the top four components were naringin, neohesperidin, synephrine, and nodakenin. The OPLS-DA classified the samples into three categories, and the variable importance projection showed that neohesperidin, naringin, nodakenin, and rhein had a greater impact on the benchmarking of Sanhua Tang substances. Network pharmacology predicted that the 13 active compounds might exert their pharmacodynamic effects through 38 core targets such as TP53, Akt1, HSP90AA1, SRC, PIK3CA, as well as 157 major pathways such as endocrine resistance, lipid and atherosclerosis, prostate cancer, colorectal cancer, and PI3K-Akt1 signaling pathway. The top five components were emodin, chrysophanol, physcioner, honokiol, and magnolol. The molecular docking results showed that 13 components could bind stably to the Akt1.Conclusion By integrating content determination, chemometrics, and network pharmacology, a total of 10 components, including rhein, emodin, physcioner, chrysophanol, naringin, neohesperidin, synephrine, magnolol, honokiol, and nodakenin were screened as they may be quality markers for the Sanhua Tang.