A Serum Pharmacochemistry and Network Pharmacology-based Approach to Study the Anti-depressant Effect of Chaihu-Shugan San

Deng MF, Yan YZ, Zhu SS, Zhou K, Tan SJ, Zeng P · Combinatorial Chemistry & High Throughput Screening · 2025 January

DOI 10.2174/0113862073285198240322072301

Objective

To investigate the chemical components and mechanisms by which Chaihu-Shugan San produces antidepressant effects through liver and brain targets using serum medicinal chemistry, network pharmacology, proteomics, and high-throughput data.

Conclusions

This study demonstrates that Chaihu-Shugan San produces antidepressant effects through multiple bioactive compounds targeting liver-specific and brain antidepressant-related proteins, including synapse-related proteins involved in synaptic structure and neuronal function, and identifies potential lead compounds for depression drug development.

Critical Appraisal

Published research can offer valuable insights, but a paper’s conclusions may go beyond what its results support. Critical appraisal examines the methods, findings and limitations to clarify what can reasonably be concluded—and what remains uncertain.

This article has not yet been critically appraised by the Research Hub.

Learn more about Critical Appraisal

Insights

Chaihu-Shugan San, a traditional Chinese medicine, offers potential antidepressant effects by targeting liver qi and specific synapse-related proteins in the brain.

The study used serum medicinal chemistry and network pharmacology methods to investigate the mechanisms of Chaihu-Shugan San (CHSGS) in treating depression. Initially, they screened the chemical components of CHSGS from available databases to be used in their study. Subsequently, they examined the antidepressant mechanism of CHSGS by focusing on soothing the liver and relieving depression, using serum pharmacochemistry. Proteomics and high-throughput data were further employed to ascertain the validity of CHSGS's antidepressant mechanism. The researchers identified 9 bioactive substances in CHSGS through serum medicinal chemistry. These ingredients, which included nobiletin and ferulic acid among others, were found to have good oral bioavailability and non-toxicity. Based on liver ChIPseq data, CHSGS was found to act on 8 specific targets localized in the liver. Network pharmacology analyses also linked 9 blood components of CHSGS with 63 antidepressant targets in the brain. Notably, CHSGS was validated to exert antidepressant effects on the synaptic structure and neuronal function by targeting multiple synapse-related proteins.