Screening the effective components of Suanzaoren decoction on the treatment of chronic restraint stress induced anxiety-like mice by integrated chinmedomics and network pharmacology

Abstract

Background: Suanzaoren decoction (SZRD) is a classical traditional Chinese prescription. It is widely used to treat mental disorders, including insomnia, anxiety, and depression, in China and other Asian countries. However, the effective components and mechanisms underlying SZRD remained unclear.

Purpose: We aimed to develop a new strategy to discover the effects and potential mechanisms of SZRD against anxiety and to further reveal the effective components of SZRD in treating anxiety.

Study design and methods: First, the chronic restraint stress (CRS)-induced mouse model of anxiety was orally administered SZRD, and behavioral indicators and biochemical parameters were applied to assess efficacy. A chinmedomics strategy based on UHPLC-Q-TOF-MS technology and network pharmacology were then used to screen and explore potentially effective components and therapeutic mechanisms. Finally, molecular docking was applied to further confirm the effective components of SZRD, and a multivariate network for anxiolytic effects was constructed.

Results: SZRD exerted anxiolytic effects by increasing the percentage of entries into open arms and the time spent in open arms; improving hippocampal 5-HT, GABA, and NE levels; and increasing serum corticosterone (CORT) and corticotropin-releasing hormone (CRH) levels caused by CRS challenge. Beside, SZRD exerted a sedative effect by decreasing sleep time and prolonging sleep latency with no muscle relaxation effect in CRS mice. A total of 110 components were identified in SZRD, 20 of which were absorbed in the blood. Twenty-one serum biomarkers involved in arachidonic acid, tryptophan, sphingolipid, and linoleic acid metabolism were identified after SZRD intervention. Finally, a multivariate network including prescription-effective components-targets-pathway of SZRD treating anxiety, including 11 effective components, 4 targets and 2 pathway was constructed.

Conclusion: The current study demonstrated that integrating chinmedomics and network pharmacology was a powerful approach to investigating the effective components and therapeutic mechanisms of SZRD and provided a solid basis for the quality marker (Q-marker) of SZRD.

Keywords: Anxiety; Chinmedomics; Chronic restraint stress; Network pharmacology; Suanzaoren decoction; The effective components.