Molecular mechanisms of Chengshi Beixie Fenqing Decoction based on network pharmacology: pivotal roles of relaxin signaling pathway and its associated target proteins against Benign prostatic hyperplasia

Abstract

Benign prostatic hyperplasia (BPH) is a common disease that affects the quality of life of middle-aged and older men. We investigated the therapeutical effects of Chengshi Beixie Fenqing Decoction (CBFD), a classic traditional Chinese medicine prescription, on BPH through in vivo model and network pharmacology. Bioactives in CBFD were detected through UPLC-Q-Tof-MS/MS and GC-MS, and filtered by the modified Lipinski’s rule. Target proteins associated with the filtered compounds and BPH are selected from public databases. Venn diagram identified the overlapping target proteins between the bioactives-interacted target proteins and the BPH-targeted proteins. The bioactive-protein interactive networking of BPH was analyzed through the KEGG pathway on STRING to identify potential ligand-target and visualized the rich factors on the R packet. After that, the molecular docking test (MDT) was performed between bioactives and target proteins. It showed that the mechanism of CBFD against BPH was related to 104 signaling pathways of 42 compounds. AKT1, 6-demethyl-4′-methyl-N-methylcoclaurine and relaxin signaling pathways were selected as a hub target, key bioactivitie and hub signaling pathway, respectively. In addition, three major compounds, 6-demethyl-4′-methyl-N-methylcoclaurine, isoliensinine and liensinine, had the highest affinity on MDT for the three crucial target proteins, AKT1, JUN and MAPK1. These proteins were associated with the relaxin signaling pathway, which regulated the level of nitric oxide and is implicated in both BPH development and CBFD. We concluded that the three key bioactivities found in Plumula nelumbinis of CBFD may contribute to improving BPH condition by activating the relaxin signaling pathways.

Communicated by Ramaswamy H. Sarma

Keywords:

• Chengshi Beixie Fenqing Decoction
• a classic traditional Chinese medicine prescription
• network pharmacology
• benign prostatic hyperplasia
• relaxin signaling pathway

Disclosure Statement

There are no conflicts of interest declared.

Ethics Statement

All experimental protocols of animals were strictly conformed to the guidelines for the Guide of the Care and Use of Laboratory Animals (NIH Publication, 1996) and were approved by the Ethical Committee of Nanjing University of Chinese Medicine (No. 202209A048).

Approval and Consent to Participate

This research was approved by the School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing, Jiangsu, 210023, China.

Authors’ Contributions

Conceptualization, Methodology, Formal analysis, Investigation, Visualization, Data Curation and Writing of Original Draft, P. Hu and Y. Pan; Software, Investigation, Data Curation, B-H. Yan, Q-X. Xu and M-T. Gao; Validation, Review and Editing, X. Ge and Y. Li; Supervision, Project administration, Y. Pan. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

All data are included in the main text or supplementary materials. All data generated or analyzed during this study are included in this published article (and its Supplementary Information files).

Additional information

Funding

This research was supported by the National Natural Science Foundation of China (81373295, 82204420), Natural Science Foundation of Jiangsu province (BK20220474), The Natural Science Foundation of the Jiangsu Higher Education Institutions of China (22KJB310004), the Open Project of the State Key Laboratory of Natural Medicines (SKLNMKF202202), and the Funding Supporting Projects of National Natural Science Foundation of China (XPT82204420).