School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Biomed Chromatogr. 2022 May;36(5):e5305. doi: 10.1002/bmc.5305. Epub 2022 Feb 7.
Dahuang Zhechong Pill (DHZCP) is a traditional Chinese medicine prescription used to treat many diseases especially chronic liver disease accompanied by promotion of vascular normalization. In this work, UPLC-Q-TOF-MS/MS analysis was applied to identify the chemical components absorbed in the blood. HIF-1α, VEGF, Ang2 and Tie2 related to vascular normalization were detected to determine the dynamic changes of pharmacodynamic indicators. Then, the spectrum-effect relationship between the UHPLC fingerprint and pharmacodynamic indicators was evaluated dynamically using partial least squares (PLS). As a result, 103 components were identified from rat serum samples, including 56 original compounds and 47 metabolites. According to the PLS, active constituents of DHZCP acting on HIF-1α, VEGF, Ang2 and Tie2 (8, 15, 17 and 20) were found. In subsequent experiments on cells, 7/11 components of HIF-1α/VEGF were found in HepG2 and HUVEC cells, and 11/14/2 components of HIF-1α/VEGF/Tie2. The main pharmacodynamic components of DHZCP in promoting vascular normalization were successfully identified by the spectrum-effect relationship analysis.
大黄䗪虫丸是一种用于治疗多种疾病的中药方剂,尤其在治疗伴有血管新生正常化的慢性肝病方面具有显著疗效。本研究采用 UPLC-Q-TOF-MS/MS 分析方法,鉴定了入血的化学成分。检测了与血管新生正常化相关的 HIF-1α、VEGF、Ang2 和 Tie2,以确定药效指标的动态变化。然后,采用偏最小二乘法(PLS)对 UHPLC 指纹图谱与药效指标之间的谱效关系进行了动态评价。结果从大鼠血清样品中鉴定出 103 个成分,包括 56 个原型化合物和 47 个代谢产物。根据 PLS 分析,发现大黄䗪虫丸作用于 HIF-1α、VEGF、Ang2 和 Tie2 的活性成分(8、15、17 和 20)。在后续的细胞实验中,在 HepG2 和 HUVEC 细胞中发现了 7/11 个 HIF-1α/VEGF 成分,在 HepG2 和 HUVEC 细胞中发现了 11/14/2 个 HIF-1α/VEGF/Tie2 成分。通过谱效关系分析,成功鉴定出大黄䗪虫丸促进血管新生正常化的主要药效成分。