Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract

Rui Xu; Hengyuan Yu; Yichen Wang; Boyu Li; Yong Chen; Xuesong Liu; Tengfei Xu

doi:10.1016/j.jpha.2024.101101

Volume 15 Issue 2

Feb. 2025

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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[J]. Journal of Pharmaceutical Analysis, 2025, 15(2): 101101. doi: 10.1016/j.jpha.2024.101101

Citation:

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[J]. Journal of Pharmaceutical Analysis, 2025, 15(2): 101101. doi: 10.1016/j.jpha.2024.101101

Citation:

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[J]. Journal of Pharmaceutical Analysis, 2025, 15(2): 101101. doi: 10.1016/j.jpha.2024.101101

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Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract

doi: 10.1016/j.jpha.2024.101101

Rui Xu^a,b,
Hengyuan Yu^a,b,
Yichen Wang^a,c,
Boyu Li^a,b,
Yong Chen^a,b,
Xuesong Liu^a,b,c,
Tengfei Xu^{a,b,d
,
,}

a. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China;
b. Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China;
c. Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310058, China;
d. Research Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

Funds:

This work was supported by the National Natural Science Foundations of China (Grant No.: 82204584) and Liaoning Provincial Science and Technology Projects, China (Project No.: 2021JH1/10400055).

Received Date: Jun. 14, 2024
Accepted Date: Sep. 10, 2024
Rev Recd Date: Aug. 29, 2024
Publish Date: Sep. 16, 2024

Abstract

Abstract

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.
- NP-VIP strategy,
- Target identification,
- Natural products,
- Salvia miltiorrhiza

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References(50)

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