Elucidation of the Mechanisms and Molecular Targets of Run-zao-zhiyang Capsule for Itch based on Network Pharmacology, Molecular Docking and In Vitro Experiment

Abstract

Background: Traditional Chinese medicine formula (TCMF) Run-zao-zhi-yang capsule (RZZY) is commonly used in treating itch in China. However, there are few studies on its mechanisms. In this study, we revealed the mechanisms and molecular targets of RZZY for itch by network pharmacology, molecular docking, and in vitro experiments.

Methods: The network pharmacology consisted of active ingredient collection, target acquisition, enrichment analysis, biological process analysis, and network construction. Molecular docking was carried out using molegro virtual docker (MVD) software. LPS-induced RAW 264.7 cells were used to evaluate the in vitro anti-inflammatory activity.

Results: We collected 483 high-confidence targets that interacted with 16 active compounds of RZZY, including 121 common genes related to itch. 43 important targets and 20 important pathways were identified according to the network and system analysis. Target-pathway network function analysis suggested that RZZY is treated for itch by multiple ways in immune regulation, hormone adjustment, anti-inflammation, and anti-oxidation. Molecular docking results demonstrated that daidzein and formononetin could be closely combined with 4 proteins. In vitro experiments displayed that RZZY, sophocarpine, catalpol, emodin, and daidzein had suppressive effects against TNF-α, IL-1β, or IL-6 production in LPS-induced RAW 264.7 cells. Interestingly, the result of network pharmacology revealed that RZZY might be more suitable for senile pruritus, consistent with the bibliometric analysis of RZZY's clinical indications.

Conclusion: This study illustrated the potential mechanisms and molecular targets of RZZY for itch, which may contribute to the proper use of RZZY in clinical practice.

Keywords: MVD; Run-zao-zhi-yang capsule; anti-inflammation; itch; molecular docking; network pharmacology.