目的 在考虑中药整体观特点前提下,采用虚拟筛选-成分敲除-效应成分指数联合的新策略,筛选通关藤潜在质量标志物(quality marker,Q-Marker),并建立以临床功效为导向的基于效应成分指数的通关藤质量评价新方法。方法 采用网络药理学,虚拟筛选通关藤抗肿瘤潜在Q-Marker;通过成分敲除方法,以H₂₂荷瘤小鼠为模型,验证潜在Q-Marker筛选的正确性;采用高效液相色谱-紫外检测器-蒸发光散射检测器(HPLC-VWD-ELSD)技术,测定30批药材中各潜在Q-Marker的含量,并以人胃癌细胞HGC-27、人肝癌细胞SMMC-7721为体外模型,检测各Q-Marker对22种细胞的生长抑制率;最后结合自定义权重系数分配法,建立基于潜在Q-Marker含量和药效值的效应成分指数方法。结果 确定了通关藤抗肿瘤的潜在Q-Marker为通关藤苷G、通关藤苷H和通关藤苷I,三者药效可达药材整体药效的50%以上;建立的效应成分指数与HGC-27、SMMC-7721细胞抑制率呈显著正相关,r分别为0.757、0.884,说明效应成分指数越大,抗肿瘤药效越强。结论 采用虚拟筛选-成分敲除-效应成分指数联合新策略,构建了“以效论质、效从质变”的通关藤质量评价新模式,兼顾了中药质量整体性和临床特异性的双重属性,为中药质量评价提供新思路。

Objective Considering the holistic characteristics of traditional Chinese medicine (TCM), a novel integrated strategy combining virtual screening, component knockout, and the efficacy component index (ECI) was employed to screen for potential quality markers (Q-Markers) of Marsdenia tenacissima and establish a novel clinical efficacy-oriented quality assessment method based on the ECI. Methods Network pharmacology was first used to virtually screen for anti-tumor potential Q-Markers of M. tenacissima. The accuracy of marker screening was then verified using the component knockout method in H₂₂ tumor-bearing mice. The contents of each identified marker in 30 batches of medicinal material were determined using HPLC-VWD-ELSD technology. The growth inhibition rates of these markers against 22 types of cells were assessed, with HGC-27 and SMMC-7721 cells as in vitro models. Finally, an ECI method based on potential Q-Marker content and efficacy value was established by integrating a custom weight coefficient assignment method. Results The results identified tenacissosides G, H, and I as the anti-tumor Q-Markers of M. tenacissima, collectively accounting for over 50% of the whole herb’s efficacy. The established ECI showed significant positive correlations with the inhibition rates against HGC-27 and SMMC-7721 cells (correlation coefficients r of 0.747 and 0.884, respectively), indicating that a higher ECI corresponds to stronger anti-tumor efficacy. Conclusion The integrated “virtual screening-component knockout-ECI” strategy established a novel quality assessment model for M. tenacissima, characterized as “quality assessment based on efficacy” and “efficacy changes with quality variation”. This model addresses the dual attributes of holistic quality and clinical specificity in TCM, providing a new approach for TCM quality evaluation.

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国家自然科学基金面上项目（82173935）；辽宁省自然科学基金博士启动项目（2024-BS-134）；辽宁省教育厅面上项目（LJKMZ20221312）；辽宁省教育厅重点攻关项目（JYTZD2023198）；国家中管局全国老药工（康廷国）传承工作室建设项目