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Study on the material basis of Dahuang Zhechong pill of anti-hepatoma effect by promoting vascular normalization
Authors:Honglin Chen  Furong Yang  Chuankui Fu  Zimeng Zhang  Kejia Xu  Shengfeng Lu  Zhipeng Chen  Li Wu  Weidong Li
Affiliation:1. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China;2. Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China;3. Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China
Abstract: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.
Keywords:Dahuang Zhechong Pill  hepatocellular carcinoma  spectrum–effect relationship  UHPLC–Q-TOF–MS/MS  vascular normalization
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