Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210029, Jiangsu, China; Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu, China.
Children's Hospital of Soochow University, Suzhou 215025, Jiangsu, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118848. doi: 10.1016/j.jep.2024.118848. Epub 2024 Sep 21.
Quality control is a critical element for Traditional Chinese medicine (TCM). Due to the varied chemical components, mechanisms of action, and pharmacological functions in TCM, ensuring quality is more challenging compared to chemical drugs. Then, the concept of quality markers (Q-markers) was proposed and ideal Q-markers for TCM prescriptions need to compliant with "five principles", including pharmacological effectiveness, specificity, transfer and traceability, measurability, and prescription compatibility.
To establish a mathematical multiple-dimensional "spider-web" strategy and identify the Q-markers of Tianshu capsule (TSC), a Chinese patent medicine for the treatment of migraine, following the "five principles" rules.
Q-marker candidates of TSC were firstly screened according to the HPLC fingerprints. Their contents in 10 batches of TSC and stabilities under high temperature, high humidity and in work solutions were determined quantitatively by HPLC-UV (measurability). Their existences in Gastrodiae Rhizoma, Chuanxiong Rhizoma, TSC, rat plasma and brain samples were investigated using HPLC-Q-TOF/MS (transfer and traceability). Their anti-migraine efficacies were evaluated by network pharmacology and mice hot-plate analgesia test; and their relationships with the property (flavor) of Gastrodiae Rhizoma or Chuanxiong Rhizoma were studied by molecular docking (effectiveness). Their contributions were defined based on their herb source according to the compatibility theories of Da Chuan Xiong Fang (compatibility). Their biosynthetic pathways were studied, and their frequencies detected in different plant families were calculated (specificity). Finally, an eight dimensional "spider-web" mode was developed for 10 components, and the regression area (RA) and the coefficient variation (CV) of each candidate were calculated after data normalization.
Ten components including gastrodin, parishin E, chlorogenic acid, ferulic acid, isochlorogenic acid A, senkyunolide I, H, A, Z-ligustilide and levistilide A were selected and evaluated as the Q-marker candidates. The results showed that gastrodin, senkyunolide I, and senkyunolide A had the higher RA and lower CV than other compounds with the established "spider-web" mode, indicating that they could be used as the Q-markers of TSC.
The multi-dimensional "spider-web" mode based on "five principles" was firstly applied to identify the Q-markers of TSC, and it can be used as a practical strategy to discover Q-markers of other compounded prescriptions.
质量控制是中药（TCM）的关键要素。由于 TCM 中化学物质成分、作用机制和药理学功能的多样性，与化学药物相比，确保质量更具挑战性。因此，提出了质量标志物（Q-标志物）的概念，TCM 处方的理想 Q-标志物需要符合“五个原则”，包括药理学功效、特异性、可传递性和可追溯性、可测量性和处方兼容性。
根据“五个原则”规则，建立一种多维“蛛网”策略，并确定用于治疗偏头痛的中药天舒胶囊（TSC）的 Q-标志物。
首先根据 HPLC 指纹图谱筛选 TSC 的 Q-标志物候选物。通过 HPLC-UV（可测量性）定量测定 10 批 TSC 中的含量及其在高温、高湿和工作溶液中的稳定性。使用 HPLC-Q-TOF/MS（可传递性和可追溯性）研究其在天麻、川芎、TSC、大鼠血浆和脑组织样本中的存在情况。通过网络药理学和小鼠热板镇痛试验评价其抗偏头痛功效；并通过分子对接（功效）研究其与天麻或川芎药性（味）的关系。根据大川芎方的配伍理论，根据其草药来源定义其贡献（兼容性）。研究其生物合成途径，并计算其在不同植物科中的检出频率（特异性）。最后，为 10 种成分建立了一个八维“蛛网”模式，并在数据归一化后计算每个候选物的回归面积（RA）和系数变化（CV）。
筛选出包括天麻素、parishin E、绿原酸、阿魏酸、异绿原酸 A、升麻素 I、H、A、Z-藁本内酯和左旋延胡索乙素在内的 10 种成分作为 Q-标志物候选物。结果表明，天麻素、升麻素 I 和升麻素 A 与所建立的“蛛网”模式相比，具有更高的 RA 和更低的 CV，表明它们可作为 TSC 的 Q-标志物。
首次将基于“五个原则”的多维“蛛网”模式应用于 TSC 的 Q-标志物鉴定，可作为发现其他复方制剂 Q-标志物的实用策略。
