目的 在考慮中藥整體觀特點前提下,采用虛擬篩選-成分敲除-效應(yīng)成分指數(shù)聯(lián)合的新策略,篩選通關(guān)藤潛在質(zhì)量標志物(quality marker,Q-Marker),并建立以臨床功效為導(dǎo)向的基于效應(yīng)成分指數(shù)的通關(guān)藤質(zhì)量評價新方法。方法 采用網(wǎng)絡(luò)藥理學(xué),虛擬篩選通關(guān)藤抗腫瘤潛在Q-Marker;通過成分敲除方法,以H₂₂荷瘤小鼠為模型,驗證潛在Q-Marker篩選的正確性;采用高效液相色譜-紫外檢測器-蒸發(fā)光散射檢測器(HPLC-VWD-ELSD)技術(shù),測定30批藥材中各潛在Q-Marker的含量,并以人胃癌細胞HGC-27、人肝癌細胞SMMC-7721為體外模型,檢測各Q-Marker對22種細胞的生長抑制率;最后結(jié)合自定義權(quán)重系數(shù)分配法,建立基于潛在Q-Marker含量和藥效值的效應(yīng)成分指數(shù)方法。結(jié)果 確定了通關(guān)藤抗腫瘤的潛在Q-Marker為通關(guān)藤苷G、通關(guān)藤苷H和通關(guān)藤苷I,三者藥效可達藥材整體藥效的50%以上;建立的效應(yīng)成分指數(shù)與HGC-27、SMMC-7721細胞抑制率呈顯著正相關(guān),r分別為0.757、0.884,說明效應(yīng)成分指數(shù)越大,抗腫瘤藥效越強。結(jié)論 采用虛擬篩選-成分敲除-效應(yīng)成分指數(shù)聯(lián)合新策略,構(gòu)建了“以效論質(zhì)、效從質(zhì)變”的通關(guān)藤質(zhì)量評價新模式,兼顧了中藥質(zhì)量整體性和臨床特異性的雙重屬性,為中藥質(zhì)量評價提供新思路。

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.

R286.2

國家自然科學(xué)基金面上項目（82173935）；遼寧省自然科學(xué)基金博士啟動項目（2024-BS-134）；遼寧省教育廳面上項目（LJKMZ20221312）；遼寧省教育廳重點攻關(guān)項目（JYTZD2023198）；國家中管局全國老藥工（康廷國）傳承工作室建設(shè)項目