Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract
Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phe...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177924001989 |
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| author | Rui Xu Hengyuan Yu Yichen Wang Boyu Li Yong Chen Xuesong Liu Tengfei Xu |
| author_facet | Rui Xu Hengyuan Yu Yichen Wang Boyu Li Yong Chen Xuesong Liu Tengfei Xu |
| author_sort | Rui Xu |
| collection | DOAJ |
| description | Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations. |
| format | Article |
| id | doaj-art-b0b1e73b05894fedb336b65410866642 |
| institution | Kabale University |
| issn | 2095-1779 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj-art-b0b1e73b05894fedb336b654108666422025-01-31T05:11:14ZengElsevierJournal of Pharmaceutical Analysis2095-17792025-02-01152101101Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extractRui Xu0Hengyuan Yu1Yichen Wang2Boyu Li3Yong Chen4Xuesong Liu5Tengfei Xu6College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Research Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Corresponding author. Research Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.http://www.sciencedirect.com/science/article/pii/S2095177924001989NP-VIP strategyTarget identificationNatural productsSalvia miltiorrhiza |
| spellingShingle | Rui Xu Hengyuan Yu Yichen Wang Boyu Li Yong Chen Xuesong Liu Tengfei Xu Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract Journal of Pharmaceutical Analysis NP-VIP strategy Target identification Natural products Salvia miltiorrhiza |
| title | Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract |
| title_full | Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract |
| title_fullStr | Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract |
| title_full_unstemmed | Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract |
| title_short | Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract |
| title_sort | natural product virtual interact phenotypic target characterization a novel approach demonstrated with salvia miltiorrhiza extract |
| topic | NP-VIP strategy Target identification Natural products Salvia miltiorrhiza |
| url | http://www.sciencedirect.com/science/article/pii/S2095177924001989 |
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