Guo Zheng1, Lu Gan2, Li-Ying Jia3, De-Cui Zhou4, Sheng Bi5, Zhao-Qing Meng6, Gui-Ju Guan7, Meng-Meng Huang8, Xin He9, Chun-Feng Zhang10, Chong-Zhi Wang11, Chun-Su Yuan12. 1. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: 545234511@qq.com. 2. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: 793116709@qq.com. 3. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: 2399187823@qq.com. 4. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: 2356914279@qq.com. 5. Shandong Hongjitang Pharmaceutical Group Co., Ltd, Jinan, 250103, PR China. Electronic address: bisheng@linuo.com. 6. Shandong Hongjitang Pharmaceutical Group Co., Ltd, Jinan, 250103, PR China. Electronic address: mengzq@linuo.com. 7. Shandong Hongjitang Pharmaceutical Group Co., Ltd, Jinan, 250103, PR China. Electronic address: guangj@hjt.cn. 8. Shandong Hongjitang Pharmaceutical Group Co., Ltd, Jinan, 250103, PR China. Electronic address: huangmm@hjt.cn. 9. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: xhe06@qub.ac.uk. 10. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: zhangchunfeng67@163.com. 11. Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA. Electronic address: cwang@dacc.uchicago.edu. 12. Tang Center of Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL, 60637, USA. Electronic address: cyuan@dacc.uchicago.edu.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Duijinsan (DJS) is a famous Chinese medicine prescription composed of Radix scutellariae (RS) and Rhei Radix (RRR), which has been mainly used for treating migraine. AIM OF THE STUDY: This study aimed to uncover the anti-migraine active compounds from DJS and preliminary predicted the pharmacological mechanism by evaluating the spectrum-effect relationship between high-performance liquid chromatography (HPLC) fingerprints and anti-migraine effects of Duijinsan (DJS) extract combined with molecular docking. MATERIALS AND METHODS: HPLC and LC-MS were applied for chemical analyses of DJS extracts in different proportions. Inhibition of DJS extracts on trigeminal nerve cell releasing calcitonin gene related peptide (CGRP) experiment was performed. The active compounds were screened by spectrum-effect relationship analysis and confirmed by molecular docking and the activities of major predicted compounds were validated in vitro. RESULTS: Twenty-six common peaks were assigned and identified from the fingerprints of different proportions DJS extracts. In vitro experimental results showed that DJS extracts inhibited inflammation and release of CGRP from trigeminal nerve cells. Five predicted active compounds, Chrysin 6-C-arabinoside 8-C-glucoside, Chrysin 6-C-glucoside 8-C-arabinoside, baicalin, Chrysin-7-O-Beta-D-glucoronide and Oroxylin A 7-O-glucuronide were sorted out according to spectrum-effect relationship analysis and molecular docking comprehensively. In vitro validation experiments showed that all the predicted compounds inhibited the CGRP releasing and the activation of TRPV1 channel. Baicalin, chrysin-7-O-β-D-glucuronide and Oroxylin A-7-glucoronide significantly inhibited the activation of TRPV1 channel. CONCLUSION: Chrysin 6-C-arabinoside 8-C-glucoside, Chrysin 6-C-glucoside 8-C-arabinoside, baicalin, Chrysin-7-O-Beta-D-glucoronide and Oroxylin A 7-O-glucuronide which can inhibit the CGRP releasing and the activation of TRPV1 channel were screened as the anti-migraine active compounds by spectrum-effect relationship analysis and molecular docking.
ETHNOPHARMACOLOGICAL RELEVANCE: Duijinsan (DJS) is a famous Chinese medicine prescription composed of Radix scutellariae (RS) and Rhei Radix (RRR), which has been mainly used for treating migraine. AIM OF THE STUDY: This study aimed to uncover the anti-migraine active compounds from DJS and preliminary predicted the pharmacological mechanism by evaluating the spectrum-effect relationship between high-performance liquid chromatography (HPLC) fingerprints and anti-migraine effects of Duijinsan (DJS) extract combined with molecular docking. MATERIALS AND METHODS: HPLC and LC-MS were applied for chemical analyses of DJS extracts in different proportions. Inhibition of DJS extracts on trigeminal nerve cell releasing calcitonin gene related peptide (CGRP) experiment was performed. The active compounds were screened by spectrum-effect relationship analysis and confirmed by molecular docking and the activities of major predicted compounds were validated in vitro. RESULTS: Twenty-six common peaks were assigned and identified from the fingerprints of different proportions DJS extracts. In vitro experimental results showed that DJS extracts inhibited inflammation and release of CGRP from trigeminal nerve cells. Five predicted active compounds, Chrysin 6-C-arabinoside 8-C-glucoside, Chrysin 6-C-glucoside 8-C-arabinoside, baicalin, Chrysin-7-O-Beta-D-glucoronide and Oroxylin A 7-O-glucuronide were sorted out according to spectrum-effect relationship analysis and molecular docking comprehensively. In vitro validation experiments showed that all the predicted compounds inhibited the CGRP releasing and the activation of TRPV1 channel. Baicalin, chrysin-7-O-β-D-glucuronide and Oroxylin A-7-glucoronide significantly inhibited the activation of TRPV1 channel. CONCLUSION: Chrysin 6-C-arabinoside 8-C-glucoside, Chrysin 6-C-glucoside 8-C-arabinoside, baicalin, Chrysin-7-O-Beta-D-glucoronide and Oroxylin A 7-O-glucuronide which can inhibit the CGRP releasing and the activation of TRPV1 channel were screened as the anti-migraine active compounds by spectrum-effect relationship analysis and molecular docking.