College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Department of Cardiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China; Key Laboratory of State Administration of Traditional Chinese Medicine, Sunshine Lake Pharma Co., LTD, Dongguan, Guangdong 523850, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jun 15;1175:122729. doi: 10.1016/j.jchromb.2021.122729. Epub 2021 Apr 20.
Huo-Tan-Chu-Shi Decoction (HTCSD), a traditional Chinese medicine (TCM) prescription within Guangdong Provincial TCM Hospital (the largest TCM hospital in China), is used for effective clinical treatment of coronary heart disease (CHD) caused by phlegm-dampness syndrome with high incidence in the hot and humid climate of Lingnan region. However, its chemical components responsible for the therapeutic effects remain unclear, which restricts its application and further development. Hence, a detailed workflow, combing with UHPLC-Q/TOF-MS, network pharmacology analysis and experimental verification, was proposed and applied to characterize the chemical profile and potential mechanism of HTCSD against CHD. As a result, a total of 130 components from all six composed herbal medicines were characterized in a rapid and sensitive manner through UHPLC-Q/TOF-MS, of which 33 compounds were unambiguously confirmed with reference standards. Consequently, based on the integrated pharmacology network of "herbs-chemicals-targets-pathways-therapeutic effects", four chemicals (magnoflorine, menisperine, 13-hydroxyberberine, luteolin) with four CHD related targets (SRC, MAPK1, EGFR and AKT1) were considered as the key components and targets of HTCSD in the treatment of CHD. Furthermore, the effect of HTCSD was confirmed in animal experiments by enhancing the phosphorylation of MAPK, and the published literature and molecular binding results suggested that magnoflorine and luteolin tended to be the critical compounds involved in the process. Taken together, the characterization of chemical profile combined with network pharmacology analysis and experimental verification not only provided an efficient insight into the overall chemical profile of HTCSD but also revealed the potential pharmacological components and mechanisms of HTCSD against CHD, which laid a necessary chemical and biological basis for the discovery of in vivo bioactive components and the further revelation of functionary mechanism.
藿痰逐瘀汤（HTCSD）是广东省中医院（中国最大的中医院）的一种中药方剂，用于有效治疗岭南地区湿热气候高发的痰浊阻络型冠心病（CHD）。然而，其治疗效果的化学成分仍不清楚，这限制了其应用和进一步发展。因此，提出并应用了一个详细的工作流程，结合 UHPLC-Q/TOF-MS、网络药理学分析和实验验证，以表征 HTCSD 治疗 CHD 的化学特征和潜在机制。结果，通过 UHPLC-Q/TOF-MS 快速灵敏地鉴定了来自所有六种组成草药的 130 种成分，其中 33 种化合物通过对照品得到明确确认。因此，基于“草药-化学物质-靶标-途径-治疗效果”的综合药理学网络，四个化学物质（厚朴酚、胡椒碱、13-羟基小檗碱、木樨草素）和四个 CHD 相关靶标（Src、MAPK1、EGFR 和 AKT1）被认为是 HTCSD 治疗 CHD 的关键成分和靶标。此外，HTCSD 在动物实验中的作用通过增强 MAPK 的磷酸化得到了证实，并且已发表的文献和分子结合结果表明，厚朴酚和木樨草素可能是参与该过程的关键化合物。综上所述，化学特征的表征结合网络药理学分析和实验验证不仅为 HTCSD 的整体化学特征提供了有效的见解，还揭示了 HTCSD 治疗 CHD 的潜在药理学成分和机制，为体内生物活性成分的发现和功能机制的进一步揭示奠定了必要的化学和生物学基础。
