Uncovering the Q-marker and potential mechanisms of Qishan Formula for lung cancer based on multi-technology

Qishan Formula (QSF) is mainly used to treat lung cancer and its side effects of radiotherapy and chemotherapy. Although the clinical efficacy of QSF has been recognized, its mechanism of action and active ingredients are still unclear. This study aims to explore the potential Q-Marker of QSF and reveal its anti-lung cancer mechanism. Firstly, the fingerprints of 10 batches of QSF were established, and the potential Q-markers were screened by chemometrics, then network pharmacology and molecular docking methods were used to explore its anti-lung cancer mechanism. Finally, the potential Q-markers were quantitatively by UPLC-QDA. The results showed that 48 common peaks were identified by the established fingerprint, and calycosin, ginsenoside Rg1, atractylenolide III, atractylenolide I and ginsenoside Rb1 were screened as potential Q-Markers of QSF by chemometrics. Network pharmacology and molecular docking found that the potential Q-Markers may regulate various signaling pathways through targets such as FOS, IL6, EGFR, ESR1, MAPK1, and MAPK3, and play a therapeutic role in lung cancer. Besides, the established UPLC-QDA can also perform quality control for Q-Markers of QSF. This study can provide academic ideas and lay a foundation for the comprehensive quality control and mechanism research of QSF and other compound preparation.

芪参方（Qishan Formula, QSF）主要用于治疗肺癌及其放化疗相关不良反应。尽管芪参方的临床疗效已得到广泛认可，但其作用机制与活性成分仍尚不明确。本研究旨在探究芪参方的潜在质量标志物（Q-Marker），并揭示其抗肺癌的作用机制。首先，本研究建立了10批芪参方的指纹图谱，通过化学计量学方法筛选潜在质量标志物；随后采用网络药理学与分子对接技术，探究其抗肺癌的作用机制；最后，通过超高效液相色谱-四极杆检测器（UPLC-QDA）对潜在质量标志物进行定量分析。研究结果显示，所建立的指纹图谱共鉴定出48个共有峰，经化学计量学方法筛选得到毛蕊异黄酮（calycosin）、人参皂苷Rg1（ginsenoside Rg1）、苍术内酯Ⅲ（atractylenolide III）、苍术内酯Ⅰ（atractylenolide I）与人参皂苷Rb1（ginsenoside Rb1）作为芪参方的潜在质量标志物。网络药理学与分子对接分析结果表明，潜在质量标志物可通过FOS、IL6、EGFR、ESR1、MAPK1及MAPK3等靶点调控多条信号通路，进而发挥抗肺癌治疗作用。此外，所建立的UPLC-QDA分析方法可实现芪参方质量标志物的质量控制。本研究可为芪参方及其他中药复方制剂的全面质量控制与作用机制研究提供学术思路与研究基础。