Zhang Tianshu, Li Hongyuan, Lin Cong, Wang Xiaohui
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, Anhui, China.
Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, China.
Sci Rep. 2025 Apr 1;15(1):11103. doi: 10.1038/s41598-025-95994-9.
Despite the long history of Traditional Chinese Medicine (TCM) in disease treatment, the underlying "Jun-Chen-Zuo-Shi" principle remains largely unexplored. To address this gap, it is essential to elucidate the interactions between active substances in TCM through quantitative molecular and cellular pharmacology. The Chou-Talalay method is particularly effective for investigating drug combinations, making it highly relevant for TCM formulas. This study employed the Chou-Talalay method to explore the drug-drug interactions in Xuebijing (XBJ), a TCM formula used for treating sepsis. The aim was to elucidate the "Jun-Chen-Zuo-Shi" principle by investigating the interactions of the main active substances in XBJ: danshensu and salvianolic acid B (from Radix Salviae Miltiorrhizae), senkyunolide A (from Rhizoma Chuanxiong), ligustilide (from Radix Angelicae Sinensis), safflower yellow and hydroxysafflor yellow A (from Flos Carthami), and paeoniflorin (from Radix Paeoniae Rubra). We quantitatively analyzed their TLR4 antagonistic activities and used the combination index (CI) to quantify their interactions, revealing synergism (CI < 1), additive effects (CI = 1), and antagonism (CI > 1). The results show these agents inhibit nitric oxide (NO) production, with some combinations demonstrating synergistic effects at certain concentrations, while others present antagonistic effects. Understanding these interactions provides a scientific foundation for optimizing TCM formulations, enhancing quality control, efficacy, and safety.
尽管中医药在疾病治疗方面有着悠久的历史，但其 underlying “君臣佐使” 原则在很大程度上仍未得到探索。为了填补这一空白，通过定量分子和细胞药理学阐明中药中活性物质之间的相互作用至关重要。Chou-Talalay 方法在研究药物组合方面特别有效，这使其与中药方剂高度相关。本研究采用 Chou-Talalay 方法探索血必净（XBJ）中的药物相互作用，血必净是一种用于治疗脓毒症的中药方剂。目的是通过研究血必净中主要活性物质的相互作用来阐明 “君臣佐使” 原则：丹参素和丹酚酸 B（来自丹参）、川芎嗪 A（来自川芎）、藁本内酯（来自当归）、红花黄色素和羟基红花黄色素 A（来自红花）以及芍药苷（来自赤芍）。我们定量分析了它们对 TLR4 的拮抗活性，并使用组合指数（CI）来量化它们的相互作用，揭示协同作用（CI < 1）、相加作用（CI = 1）和拮抗作用（CI > 1）。结果表明这些药物抑制一氧化氮（NO）的产生，一些组合在特定浓度下表现出协同作用，而其他组合则表现出拮抗作用。了解这些相互作用为优化中药配方、加强质量控制、疗效和安全性提供了科学依据。
