Exploring the mechanism of Si-Ni-San against depression by UPLC-Q-TOF-MS/MS integrated with network pharmacology: experimental research

Keke Jia; Changyin Li; Meijuan Xu; Guoliang Dai; Jinyong Zhou; Biqing Chen; Jiandong Zou; Jia Li; Qingyu Zhang; Wenzheng Ju

doi:10.1097/MS9.0000000000001464

Exploring the mechanism of Si-Ni-San against depression by UPLC-Q-TOF-MS/MS integrated with network pharmacology: experimental research

Ann Med Surg (Lond). 2023 Nov 7;86(1):172-189. doi: 10.1097/MS9.0000000000001464. eCollection 2024 Jan.

Authors

Keke Jia^{1

2}, Changyin Li², Meijuan Xu², Guoliang Dai², Jinyong Zhou³, Biqing Chen³, Jiandong Zou², Jia Li¹, Qingyu Zhang¹, Wenzheng Ju²

Affiliations

¹ School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine.
² Department of Clinical Pharmacology.
³ Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, P. R. China.

Abstract

Background: Depression is becoming an urgent mental health problem. Si-Ni-San has been widely used to treat depression, yet its underlying pharmacological mechanism is poorly understood. Thus, we aim to explore the antidepressant mechanism of Si-Ni-San by chemical analysis and in-silico methods.

Methods: Compounds in Si-Ni-San were determined by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Then, bioactive compounds were obtained from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform and SwissADME, and the potential targets of which were acquired from SwissTargetPrediction. Depression-related targets were collected from GeneCards. The intersection between compound-related targets and depression-related targets were screened out, and the overlapped targets were further performed protein-protein interaction, biological functional and pathway enrichment analysis. Finally, networks of Si-Ni-San against depression were constructed and visualized by Cytoscape.

Results: One hundred nineteen compounds in Si-Ni-San were determined, of which 24 bioactive compounds were obtained. Then, 137 overlapped targets of Si-Ni-San against depression were collected. AKT1, PIK3R1, PIK3CA, mTOR, MAPK1 and MAPK8 were the key targets. Furthermore, PI3K-Akt signalling pathway, serotonergic synapse, MAPK signalling pathway and neurotrophin signalling pathway were involved in the antidepressant mechanism of Si-Ni-San. It showed that components like sinensetin, hesperetin, liquiritigenin, naringenin, quercetin, albiflorin and paeoniflorin were the mainly key active compounds for the antidepressant effect of Si-Ni-San.

Conclusions: This study demonstrated the key components, key targets and potential pharmacological mechanisms of Si-Ni-San against depression. These results indicate that Si-Ni-San is a promising therapeutic approach for treatment of depression, and may provide evidence for the research and development of drugs for treating depression.

Keywords: Si-Ni-San; UPLC-Q-TOF-MS/MS; depression; network pharmacology.