Antidepressant efficacy and Q-markers determination of Dachaihu decoction: Combining pharmacology, correlation analysis, and network pharmacology approaches

Abstract

Dachaihu decoction (DCHT) was first recorded in the Treatise on Febrile and Miscellaneous Diseases and has the effects of reconciling shaoyang, reducing heat, and treating shaoyang minghe disease, vomiting, heart disease, depression and other diseases. DCHT is often used in the modern clinical treatment of digestive diseases, depression, and accompanying depression. However, despite its clinical application, pharmacodynamic studies of the antidepressant effects of DCHT have not been carried out, and the key pharmacodynamic substances involved have not been identified. The aim of this study was to confirm the antidepressant efficacy of DCHT, screen its quality markers (Q-markers), and establish a method for the determination of Q-markers of DCHT. The optimal extraction site of DCHT was determined via a reserpine-induced depressive zebrafish model, and further exploration of the pharmacological site was conducted in mice with liver depression and spleen deficiency-type depression (LDSD). The antidepressant bioactive components of DCHT were identified via correlating ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLCQTOFMS/MS) peak areas from 10 extraction sites with pharmacodynamic effects in zebrafish and further screened via reverse traceability of the core targets involved in the key pathways enriched by network pharmacology. Q-markers were subsequently determined through the antidepressant efficacy verification of potential pharmacologically active substances using a zebrafish depression model in conjunction with the principle of measurability, followed by content determination. The 95 % ethanol extract of DCHT was identified as the best antidepression extract. Among the 41 common components identified in the 10 extracts of different DCHT extraction sites, 10 potential antidepressant components were screened and verified to to have antidepressant effects. However, the extremely low contents of SSa and SSd make them difficult to measure, and the poor separation of Wogonin from adjacent peaks make the accurate determination of its content difficult. Therefore, on the basis of the principles of effectiveness and measurability, the remaining 7 ingredients, Baicalin, Wogonoside, Baicalein, Sinensetin, Skullcapflavone II, Oroxylin A, and SSb₂, were defined as Q-markers for DCHT, and their total content was stable in the range of 0.7153∼0.7245 %. In conclusion, this study confirmed the antidepressant efficacy of DCHT and identified its antidepressant Q-marker, establishing the groundwork for further investigations into the antidepressant effect mechanism of DCHT and the creation of derivative products.