目的 基于指纹图谱与网络药理学探究补骨脂Psoraleae Fructus盐炙后对四神丸中活性成分的影响。方法 构建10批生补骨脂组（SP）与10批盐补骨脂组（YZ）的四神丸UPLC指纹图谱，运用化学模式识别技术并结合网络药理学技术构建“活性成分-药物靶点-通路”网络，筛选补骨脂炮制前后的差异活性成分，并对其进行定量分析。结果 在构建的20批四神丸UPLC指纹图谱中，共标定22个共有峰，其中指认了12个共有成分，相似度均≥0.970，主成分分析（principal component analysis，PCA）和正交偏最小二乘法-判别分析（orthogonal partial least squares-discriminant analysis，OPLS-DA）结果显示，SP组与YZ组差异明显，根据变量重要性投影（variable importance projection，VIP）值大于1为标准出筛选炮制前后的11个差异性成分，依次为峰13、12、21（补骨脂酚）、15、10（补骨脂二氢黄酮）、7、17、4（补骨脂素）、19（五味子甲素）、3、5（异补骨脂素），根据中药质量标志物“五项原则”与网络药理学筛选出补骨脂酚、补骨脂二氢黄酮、补骨脂素、五味子甲素、异补骨脂素为补骨脂炮制前后差异活性成分，并可能通过雌激素受体1（estrogen receptor 1，ESR1）、类固醇受体辅激活因子（steroid receptor coactivator，SRC）、前列腺素内过氧化物合成酶2（prostaglandin-endoperoxide synthase 2，PTGS2）等基因靶点及癌症信号通路、磷脂酰肌醇-3-激酶-蛋白激酶B（phosphatidylinositol-3-hydroxykinaseprotein kinase B，PI3K-Akt）、丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）、叉头框蛋白O（forkhead box O，FoxO）等信号通路发挥药理作用；定量测定结果显示，补骨脂盐炙后，四神丸中补骨脂二氢黄酮与五味子甲素的含量略有升高，而补骨脂素和异补骨脂素的含量呈现降低趋势，补骨脂酚则显著降低。结论 建立的UPLC指纹图谱可稳定有效地对SP组与YZ组进行区分，结合网络药理学分析盐炙前后的主要差异成分群，为补骨脂盐炙对四神丸中活性成分的影响研究提供参考。

Objective Based on fingerprint and network pharmacology, the effect of salt-processed Psoraleae Fructus on the active components in Sishen Wan was explored. Methods The UPLC fingerprints of 20 batches of raw Psoraleae Fructus groups (SP) and salt-processed Psoraleae Fructus groups (YZ) were constructed. The “active component-drug target-pathway” network was constructed by chemical pattern recognition technology combined with network pharmacology technology to screen the differential active components of Psoraleae Fructus before and after salt-processed, and the quantitative analysis was carried out. Results A total of 22 common peaks were calibrated in the UPLC fingerprints of 20 batches of Sishen Wan, of which 12 common components were identified, and the similarity was greater than 0.970. The results of principal component analysis (PCA) and orthogonal partial least squares method-discriminant analysis (OPLS-DA) showed that there was a significant difference between the SP group and the YZ group. According to the variable importance projection (VIP) value greater than 1 as the standard, a total of 11 differential components before and after processing were screened, followed by peak 13, 12, 21 (bakuchiol), 15, 10 (bavachin), 7, 17, 4 (psoralen), 19 (schisandrin A), 3, 5 (isopsoralen). According to the “five principles” of traditional Chinese medicine quality markers and network pharmacology, bakuchiol, bavachin, psoralen, schisandrin A and isopsoralen were selected as the differential active ingredients before and after processing of Psoraleae Fructus and may play a pharmacological role through gene targets such as estrogen receptor 1 (ESR1), steroid receptor coactivator (SRC), prostaglandin-endoperoxide synthase 2 (PTGS2), cancer signaling pathways, phosphatidylinositol-3-hydroxykinaseprotein kinase B (PI3K-Akt), mitogen-activated protein kinase (MAPK), forkhead box O (FoxO) signaling pathways. Quantitative determination results revealed that the salt-processed Psoraleae Fructus led to a slight increase in the contents of bavachin and schisandrin A, but a decreasing trend for psoralen and isopsoralen, along with a significant reduction in bakuchiol within Sishen Wan. Conclusion The established UPLC fingerprint can reliably distinguish the SP group and YZ group. The main differential component groups before and after salt-processed were analyzed by combining network pharmacology to provide a reference for the study of the effect of salt-processed Psoraleae Fructu on the active components in Sishen Wan.

R283.6

成都中医药大学“杏林学者”学科人才科研提升计划（QJRC2023014）；国家中医药管理局胡昌江全国老药工传承工作室建设项目；中华中医药学会青年人才托举工程（CACM-2023-QNRC2-B15）