Polypharmacology of Berberine Based on Multi-Target Binding Motifs
Background: Polypharmacology is emerging as the next paradigm in drug discovery. However, considerable challenges still exist for polypharmacology modeling. In this study, we developed a rational design to identify highly potential targets (HPTs) for polypharmacological drugs, such as berberine.Meth...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00801/full |
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| author | Ming Chu Ming Chu Xi Chen Jing Wang Likai Guo Likai Guo Qianqian Wang Qianqian Wang Zirui Gao Jiarui Kang Mingbo Zhang Jinqiu Feng Jinqiu Feng Qi Guo Binghua Li Binghua Li Chengrui Zhang Chengrui Zhang Xueyuan Guo Xueyuan Guo Zhengyun Chu Yuedan Wang Yuedan Wang |
| author_facet | Ming Chu Ming Chu Xi Chen Jing Wang Likai Guo Likai Guo Qianqian Wang Qianqian Wang Zirui Gao Jiarui Kang Mingbo Zhang Jinqiu Feng Jinqiu Feng Qi Guo Binghua Li Binghua Li Chengrui Zhang Chengrui Zhang Xueyuan Guo Xueyuan Guo Zhengyun Chu Yuedan Wang Yuedan Wang |
| author_sort | Ming Chu |
| collection | DOAJ |
| description | Background: Polypharmacology is emerging as the next paradigm in drug discovery. However, considerable challenges still exist for polypharmacology modeling. In this study, we developed a rational design to identify highly potential targets (HPTs) for polypharmacological drugs, such as berberine.Methods and Results: All the proven co-crystal structures locate berberine in the active cavities of a redundancy of aromatic, aliphatic, and acidic residues. The side chains from residues provide hydrophobic and electronic interactions to aid in neutralization for the positive charge of berberine. Accordingly, we generated multi-target binding motifs (MBM) for berberine, and established a new mathematical model to identify HPTs based on MBM. Remarkably, the berberine MBM was embodied in 13 HPTs, including beta-secretase 1 (BACE1) and amyloid-β1-42 (Aβ1-42). Further study indicated that berberine acted as a high-affinity BACE1 inhibitor and prevented Aβ1-42 aggregation to delay the pathological process of Alzheimer’s disease.Conclusion: Here, we proposed a MBM-based drug-target space model to analyze the underlying mechanism of multi-target drugs against polypharmacological profiles, and demonstrated the role of berberine in Alzheimer’s disease. This approach can be useful in derivation of rules, which will illuminate our understanding of drug action in diseases. |
| first_indexed | 2024-12-20T02:25:03Z |
| format | Article |
| id | doaj.art-c836279f6ba04f978b2a42a0a8bb6210 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T02:25:03Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-c836279f6ba04f978b2a42a0a8bb62102022-12-21T19:56:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-07-01910.3389/fphar.2018.00801388065Polypharmacology of Berberine Based on Multi-Target Binding MotifsMing Chu0Ming Chu1Xi Chen2Jing Wang3Likai Guo4Likai Guo5Qianqian Wang6Qianqian Wang7Zirui Gao8Jiarui Kang9Mingbo Zhang10Jinqiu Feng11Jinqiu Feng12Qi Guo13Binghua Li14Binghua Li15Chengrui Zhang16Chengrui Zhang17Xueyuan Guo18Xueyuan Guo19Zhengyun Chu20Yuedan Wang21Yuedan Wang22Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, Ministry of Health, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, Ministry of Health, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, Ministry of Health, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaDepartment of Pathology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, ChinaPharmacy Departments, Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, Ministry of Health, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, Ministry of Health, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, Ministry of Health, Peking University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, Ministry of Health, Peking University, Beijing, ChinaPharmacy Departments, Liaoning University of Traditional Chinese Medicine, Shenyang, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaKey Laboratory of Medical Immunology, Ministry of Health, Peking University, Beijing, ChinaBackground: Polypharmacology is emerging as the next paradigm in drug discovery. However, considerable challenges still exist for polypharmacology modeling. In this study, we developed a rational design to identify highly potential targets (HPTs) for polypharmacological drugs, such as berberine.Methods and Results: All the proven co-crystal structures locate berberine in the active cavities of a redundancy of aromatic, aliphatic, and acidic residues. The side chains from residues provide hydrophobic and electronic interactions to aid in neutralization for the positive charge of berberine. Accordingly, we generated multi-target binding motifs (MBM) for berberine, and established a new mathematical model to identify HPTs based on MBM. Remarkably, the berberine MBM was embodied in 13 HPTs, including beta-secretase 1 (BACE1) and amyloid-β1-42 (Aβ1-42). Further study indicated that berberine acted as a high-affinity BACE1 inhibitor and prevented Aβ1-42 aggregation to delay the pathological process of Alzheimer’s disease.Conclusion: Here, we proposed a MBM-based drug-target space model to analyze the underlying mechanism of multi-target drugs against polypharmacological profiles, and demonstrated the role of berberine in Alzheimer’s disease. This approach can be useful in derivation of rules, which will illuminate our understanding of drug action in diseases.https://www.frontiersin.org/article/10.3389/fphar.2018.00801/fullberberinepolypharmacologymulti-target binding motifsdrug-target spaceAlzheimer’s disease |
| spellingShingle | Ming Chu Ming Chu Xi Chen Jing Wang Likai Guo Likai Guo Qianqian Wang Qianqian Wang Zirui Gao Jiarui Kang Mingbo Zhang Jinqiu Feng Jinqiu Feng Qi Guo Binghua Li Binghua Li Chengrui Zhang Chengrui Zhang Xueyuan Guo Xueyuan Guo Zhengyun Chu Yuedan Wang Yuedan Wang Polypharmacology of Berberine Based on Multi-Target Binding Motifs Frontiers in Pharmacology berberine polypharmacology multi-target binding motifs drug-target space Alzheimer’s disease |
| title | Polypharmacology of Berberine Based on Multi-Target Binding Motifs |
| title_full | Polypharmacology of Berberine Based on Multi-Target Binding Motifs |
| title_fullStr | Polypharmacology of Berberine Based on Multi-Target Binding Motifs |
| title_full_unstemmed | Polypharmacology of Berberine Based on Multi-Target Binding Motifs |
| title_short | Polypharmacology of Berberine Based on Multi-Target Binding Motifs |
| title_sort | polypharmacology of berberine based on multi target binding motifs |
| topic | berberine polypharmacology multi-target binding motifs drug-target space Alzheimer’s disease |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00801/full |
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