Mingya Ding1, Wenfang Ma2, Xiaoyan Wang3, Shujing Chen4, Shuhan Zou5, Jinna Wei6, Yuqiao Yang7, Jin Li8, Xuejing Yang9, Hui Wang10, Yuhong Li11, Qilong Wang12, Haoping Mao13, Xiu-Mei Gao14, Yan-Xu Chang15. 1. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin Key Laboratory of Phytochemistry and Pharmaceutical Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: dingmingya1994@163.com. 2. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin Key Laboratory of Phytochemistry and Pharmaceutical Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: mawenfang812@126.com. 3. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: wang_xiaoyan27@163.com. 4. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: chensj0208@126.com. 5. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: cherrieszoushuhan@163.com. 6. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: 1244034099@qq.com. 7. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: tudouqiao123@163.com. 8. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin Key Laboratory of Phytochemistry and Pharmaceutical Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: zishan826@126.com. 9. School of Pharmacy, Harbin University of Commerce, Harbin, 150076, Heilongjiang, PR China. Electronic address: yangxuejing2004@126.com. 10. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin Key Laboratory of Phytochemistry and Pharmaceutical Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: tgwanghui@163.com. 11. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: liyuhong@tjutcm.edu.cn. 12. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: wangqilong_00@tjutcm.edu.cn. 13. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: maohaoping@tjutcm.edu.cn. 14. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin Key Laboratory of Phytochemistry and Pharmaceutical Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: gaoxiumei@tjutcm.edu.cn. 15. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin Key Laboratory of Phytochemistry and Pharmaceutical Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. Electronic address: Tcmcyx@tjutcm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Dan-Lou tablet (DLT) is developed from the traditional Chinese medicine (TCM) formula Gualou Xiebai Baijiu Tang which has been used for at least 2000 years in China. DLT has been widely used in clinical practice to treat cardiovascular diseases. AIM OF THE STUDY: This study aimed to uncover the pharmacological mechanism of the compounds absorbed into the blood of Dan-Lou tablet (DLT) on coronary heart disease (CHD) using a network pharmacology integrated pharmacokinetics strategy. MATERIALS AND METHODS: A rapid and sensitive method was developed for the simultaneous determination of the six compounds (puerarin, formononetin, calycosin, paeoniflorin, cryptotanshinone and tanshinone IIA) in rat plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS). Then, the pharmacology network was established based on the relationship between five compounds absorbed into the blood targets (puerarin, formononetin, calycosin, cryptotanshinone and tanshinone IIA) and CHD targets. RESULTS: The intra-and inter-day precision were less than 11% and the accuracy ranged from 88.2% to 112%, which demonstrated that the LC-MS/MS method could be used to evaluate the pharmacokinetic feature of the six compounds in rats after oral administration of DLT. The pathway enrichment analysis revealed that the significant bioprocess networks of DLT on CHD were positive regulation of estradiol secretion, negative regulation of transcription from RNA polymerase II promoter, lipopolysaccharide-mediated signaling pathway and cytokine activity. CONCLUSION: The proposed network pharmacology integrated pharmacokinetics strategy provides a combination method to explore the therapeutic mechanism of the compounds absorbed into the blood of multi-component drugs on a systematic level.
ETHNOPHARMACOLOGICAL RELEVANCE: Dan-Lou tablet (DLT) is developed from the traditional Chinese medicine (TCM) formula Gualou Xiebai Baijiu Tang which has been used for at least 2000 years in China. DLT has been widely used in clinical practice to treat cardiovascular diseases. AIM OF THE STUDY: This study aimed to uncover the pharmacological mechanism of the compounds absorbed into the blood of Dan-Lou tablet (DLT) on coronary heart disease (CHD) using a network pharmacology integrated pharmacokinetics strategy. MATERIALS AND METHODS: A rapid and sensitive method was developed for the simultaneous determination of the six compounds (puerarin, formononetin, calycosin, paeoniflorin, cryptotanshinone and tanshinone IIA) in rat plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS). Then, the pharmacology network was established based on the relationship between five compounds absorbed into the blood targets (puerarin, formononetin, calycosin, cryptotanshinone and tanshinone IIA) and CHD targets. RESULTS: The intra-and inter-day precision were less than 11% and the accuracy ranged from 88.2% to 112%, which demonstrated that the LC-MS/MS method could be used to evaluate the pharmacokinetic feature of the six compounds in rats after oral administration of DLT. The pathway enrichment analysis revealed that the significant bioprocess networks of DLT on CHD were positive regulation of estradiol secretion, negative regulation of transcription from RNA polymerase II promoter, lipopolysaccharide-mediated signaling pathway and cytokine activity. CONCLUSION: The proposed network pharmacology integrated pharmacokinetics strategy provides a combination method to explore the therapeutic mechanism of the compounds absorbed into the blood of multi-component drugs on a systematic level.