Liangliang He1, Yuehe Liu2, Kefeng Yang2, Zhenyu Zou2, Cailian Fan3, Zhihong Yao4, Yi Dai5, Keshen Li6, Jiaxu Chen7, Xinsheng Yao8. 1. The First Affiliated Hospital of Jinan University, Guangzhou 510632, PR China; College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, PR China. 2. College of Pharmacy, Jinan University, Guangzhou 510632, PR China. 3. The First Affiliated Hospital of Jinan University, Guangzhou 510632, PR China; College of Pharmacy, Jinan University, Guangzhou 510632, PR China. 4. College of Pharmacy, Jinan University, Guangzhou 510632, PR China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development Ministry of P.R. China, Jinan University, Guangzhou 510632, PR China. Electronic address: yaozhihong_jnu@163.com. 5. College of Pharmacy, Jinan University, Guangzhou 510632, PR China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development Ministry of P.R. China, Jinan University, Guangzhou 510632, PR China. Electronic address: daiyi1004@163.com. 6. The First Affiliated Hospital of Jinan University, Guangzhou 510632, PR China. 7. Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, PR China. 8. College of Pharmacy, Jinan University, Guangzhou 510632, PR China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development Ministry of P.R. China, Jinan University, Guangzhou 510632, PR China.
Abstract
BACKGROUND: Qiliqiangxin Capsule (QLQX), a traditional Chinese medicine (TCM) prescription, is especially used for clinical treatment of chronic heart failure (CHF) in China. However, the holistic quality control of QLQX has not been well established due to lack of system research on the quality marker (Q-marker). PURPOSE: In this study, a new strategy of multi-dimensional "radar chart" mode was proposed to overcome the problem that traditional methods cannot evaluate the multiple properties of Q-markers comprehensively and visually, and the strategy was successfully applied to discover the Q-markers of QLQX. METHODS: First, nineteen prototypes that entered the in vivo systemic circulation were selected out as the candidate Q-markers based on our previous studies of chemical and in vivo metabolic profiles. Then, their contents in QLQX were quantitatively analyzed by UHPLC-MS/MS, and the bioactivities on the H9c2 cardiomyocytes cell model was evaluated. The network of in vivo component-target closely related to CHF was further constructed. Finally, a multi-dimensional "radar chart" mode was developed and corresponding Regression Area (RA) and Coefficient Variation (CV) were calculated after data standardization and integration visually based on the Q-marker related multiple characteristics (including the compatibility contribution of herbal medicines, the content, the bioactivity, the in vivo predicted bioavailability and the degree of network pharmacology of candidate components in the TCM prescription). RESULTS: By comparison of RA and CV of the chemicals in the "radar chart", seven compounds mainly from King and Minister herbs (songorin, calycosin-7-O-β-D-glucopyranoside, astragaloside, tanshinone IIA, ginsenoside Re, hesperidin and alisol A) were screened out as the Q-markers of QLQX, showing the reasonable compatibility contribution and high content in QLQX, preferable pharmacological effect on CHF, as well as good bioavailable characteristics and high target hits in system pharmacology. CONCLUSION: The Q-marker discovery of QLQX in this study laid an important foundation for its quality control improvement, and the mode standardized the abstract definitions of Q-marker and realized the comprehensive assessment of multiple properties of Q-marker in TCM prescriptions, which has a reference value for revealing the Q-marker in the quality control researches of TCM prescriptions.
BACKGROUND: Qiliqiangxin Capsule (QLQX), a traditional Chinese medicine (TCM) prescription, is especially used for clinical treatment of chronic heart failure (CHF) in China. However, the holistic quality control of QLQX has not been well established due to lack of system research on the quality marker (Q-marker). PURPOSE: In this study, a new strategy of multi-dimensional "radar chart" mode was proposed to overcome the problem that traditional methods cannot evaluate the multiple properties of Q-markers comprehensively and visually, and the strategy was successfully applied to discover the Q-markers of QLQX. METHODS: First, nineteen prototypes that entered the in vivo systemic circulation were selected out as the candidate Q-markers based on our previous studies of chemical and in vivo metabolic profiles. Then, their contents in QLQX were quantitatively analyzed by UHPLC-MS/MS, and the bioactivities on the H9c2 cardiomyocytes cell model was evaluated. The network of in vivo component-target closely related to CHF was further constructed. Finally, a multi-dimensional "radar chart" mode was developed and corresponding Regression Area (RA) and Coefficient Variation (CV) were calculated after data standardization and integration visually based on the Q-marker related multiple characteristics (including the compatibility contribution of herbal medicines, the content, the bioactivity, the in vivo predicted bioavailability and the degree of network pharmacology of candidate components in the TCM prescription). RESULTS: By comparison of RA and CV of the chemicals in the "radar chart", seven compounds mainly from King and Minister herbs (songorin, calycosin-7-O-β-D-glucopyranoside, astragaloside, tanshinone IIA, ginsenoside Re, hesperidin and alisol A) were screened out as the Q-markers of QLQX, showing the reasonable compatibility contribution and high content in QLQX, preferable pharmacological effect on CHF, as well as good bioavailable characteristics and high target hits in system pharmacology. CONCLUSION: The Q-marker discovery of QLQX in this study laid an important foundation for its quality control improvement, and the mode standardized the abstract definitions of Q-marker and realized the comprehensive assessment of multiple properties of Q-marker in TCM prescriptions, which has a reference value for revealing the Q-marker in the quality control researches of TCM prescriptions.