目的 基于中药超分子（supramolecules of traditional Chinese medicine，STCM）理论，系统探讨黄芪Astragali Radix-莪术Curcumae Rhizoma（AC）药对协同增效抗肝癌的物质基础，旨在揭示其配伍的科学内涵。方法 采用离心-透析法对STCM进行分离；并借助动态光散射（dynamic light scattering，DLS）技术和透射电子显微镜（transmission electron microscope，TEM）对其粒径、形貌进行表征，结合光谱技术分析其形成机制；进一步利用液相色谱-质谱联用（liquid chromatograph mass spectrometer，LC-MS）技术分析其化学成分；并对其体外抗肝癌活性进行评价。结果 黄芪-莪术合煎液与物理混合液中均存在STCM，但黄芪-莪术合煎液中STCM（AC-STCM）的粒径更小、分布更均匀且稳定性更高；其自组装过程中可能由毛蕊异黄酮、芒柄花素、双去甲氧基姜黄素等成分通过氢键和π-π堆积作用共同驱动；AC-STCM对人肝癌HepG2细胞具有显著抑制作用（P＜0.01），其体外抗肿瘤活性显著优于合煎液、物理混合STCM（Mix-STCM）（P＜0.01），同时，合煎液本身的抗肿瘤效果亦优于物理混合液（P＜0.01）。结论 在煎煮过程中，黄芪-莪术药对通过非共价键实现成分的自组装，形成稳定的STCM体系，构成其协同增效抗肝癌作用的重要物质基础。首次从STCM的新视角阐释黄芪-莪术药对协同增效抗肝癌的科学内涵，为中药复方配伍理论的现代化研究提供理论依据与实验基础。

Objective Based on the supramolecular of traditional Chinese medicine (STCM) theory, this study systematically explored the material basis of Huangqi (Astragali Radix)-Ezhu (Curcumae Rhizoma) (AC) herb pair for synergistic anti-liver cancer, aiming to reveal the scientific connotation of its compatibility. Methods The STCM were separated by the centrifugation-dialysis method. The particle size and morphology were characterized by dynamic light scattering (DLS) technology and transmission electron microscopy (TEM), and the formation mechanism was analyzed by spectroscopic technology. The chemical composition was further analyzed by liquid chromatography-mass spectrometry (LC-MS). Its anti-liver cancer activity in vitro was evaluated. Results The results showed that STCM existed in both the AC co-decoction and the physically mixed solution, but the STCM in the co-decoction (AC-STCM) had smaller particle size, more uniform distribution, and higher stability; its self-assembly process may be jointly driven by components such as calycosin, formononetin, and demethoxycurcumin through hydrogen bonding and π-π stacking interactions. AC-STCM exhibited significant inhibitory effects on HepG2 cells (P < 0.01), with its in vitro antitumor activity notably superior to that of the co-decoction and the physically mixed STCM (Mix-STCM) (P < 0.01), while the co-decoction itself also showed better antitumor effects than the physical mixture (P < 0.01). Conclusion During the decoction process, AC herb pairs self-assemble through non-covalent bonds to form a stable STCM system, which constitutes an important material basis for their synergistic anti-liver cancer effects. This study is the first to explain the scientific connotation of AC for synergistic anti-liver cancer from the perspective of STCM, which provides a theoretical basis and experimental basis for the modernization of the theory of compound compatibility of traditional Chinese medicine.

R283

国家自然科学基金青年项目（82204656）；博士后科学基金特别资助（2024T170534）；山东省中医药科技项目（M20241725）；山东中医药大学青年创新团队支持计划（22202105）