Exploring the Mechanism of Si-Ni-San Against Depression by UPLC-Q-TOF-MS/MS Integrated with Network Pharmacology: Experimental Research

Overview

Journal Ann Med Surg (Lond)

Publisher Wolters Kluwer

Specialty Medical Education

Date 2024 Jan 15

PMID 38222693

Authors

Keke Jia

Changyin Li

Meijuan Xu

Guoliang Dai

Jinyong Zhou

Biqing Chen

Jiandong Zou

Jia Li

Qingyu Zhang

Wenzheng Ju

Affiliations

Soon will be listed here.

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.

References

Fang S, Qu Q, Zheng Y, Zhong H, Shan C, Wang F . Structural characterization and identification of flavonoid aglycones in three Glycyrrhiza species by liquid chromatography with photodiode array detection and quadrupole time-of-flight mass spectrometry. J Sep Sci. 2016; 39(11):2068-78. DOI: 10.1002/jssc.201600073. View

Zhong X, Li G, Qiu F, Huang Z . Paeoniflorin Ameliorates Chronic Stress-Induced Depression-Like Behaviors and Neuronal Damages in Rats via Activation of the ERK-CREB Pathway. Front Psychiatry. 2019; 9:772. PMC: 6339947. DOI: 10.3389/fpsyt.2018.00772. View

Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S . The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics. 2016; 54:1.30.1-1.30.33. DOI: 10.1002/cpbi.5. View

Tang M, Chen M, Li Q . Paeoniflorin ameliorates chronic stress-induced depression-like behavior in mice model by affecting ERK1/2 pathway. Bioengineered. 2021; 12(2):11329-11341. PMC: 8810059. DOI: 10.1080/21655979.2021.2003676. View

Fang K, Li H, Chen X, Gao X, Huang L, Du A . Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC. Front Pharmacol. 2020; 10:1544. PMC: 6978986. DOI: 10.3389/fphar.2019.01544. View

Zong Y, Chen T, Dong H, Zhu L, Ju W . Si-Ni-San Prevents Reserpine-Induced Depression by Inhibiting Inflammation and Regulating CYP450 Enzymatic Activity. Front Pharmacol. 2020; 10:1518. PMC: 6978689. DOI: 10.3389/fphar.2019.01518. View

Zhu Y, Wang L, Zhao D, Wang C, Zhang R, Fei W . Antidepressant-like effects of albiflorin involved the NO signaling pathway in rats model of chronic restraint stress. Chin J Nat Med. 2020; 18(11):872-880. DOI: 10.1016/S1875-5364(20)60030-9. View

Li J, Wang T, Liu P, Yang F, Wang X, Zheng W . Hesperetin ameliorates hepatic oxidative stress and inflammation the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD. Food Funct. 2021; 12(9):3898-3918. DOI: 10.1039/d0fo02736g. View

Wang B, Lu S, Zhang C, Zhu L, Li Y, Bai M . Quantitative proteomic analysis of the liver reveals antidepressant potential protein targets of Sinisan in a mouse CUMS model of depression. Biomed Pharmacother. 2020; 130:110565. DOI: 10.1016/j.biopha.2020.110565. View

10.

Li S, Zhang B . Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med. 2013; 11(2):110-20. DOI: 10.1016/S1875-5364(13)60037-0. View

11.

Artigas F, Bortolozzi A, Celada P . Can we increase speed and efficacy of antidepressant treatments? Part I: General aspects and monoamine-based strategies. Eur Neuropsychopharmacol. 2017; 28(4):445-456. DOI: 10.1016/j.euroneuro.2017.10.032. View

12.

Qiu Z, He J, Shao G, Hu J, Li X, Zhou H . Obacunone Retards Renal Cyst Development in Autosomal Dominant Polycystic Kidney Disease by Activating NRF2. Antioxidants (Basel). 2022; 11(1). PMC: 8773305. DOI: 10.3390/antiox11010038. View

13.

Malhi G, Mann J . Depression. Lancet. 2018; 392(10161):2299-2312. DOI: 10.1016/S0140-6736(18)31948-2. View

14.

Yeung W, Chung K, Ng K, Yu Y, Tat-Chi Ziea E, Ng B . A systematic review on the efficacy, safety and types of Chinese herbal medicine for depression. J Psychiatr Res. 2014; 57:165-75. DOI: 10.1016/j.jpsychires.2014.05.016. View

15.

Edinoff A, Akuly H, Hanna T, Ochoa C, Patti S, Ghaffar Y . Selective Serotonin Reuptake Inhibitors and Adverse Effects: A Narrative Review. Neurol Int. 2021; 13(3):387-401. PMC: 8395812. DOI: 10.3390/neurolint13030038. View

16.

Ma Z, Zhang R, Rui W, Wang Z, Feng X . Quercetin alleviates chronic unpredictable mild stress-induced depressive-like behaviors by promoting adult hippocampal neurogenesis via FoxG1/CREB/ BDNF signaling pathway. Behav Brain Res. 2021; 406:113245. DOI: 10.1016/j.bbr.2021.113245. View

17.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

18.

Yang J, Jin W, Liu D, Zhong Q, Zhou T . Enhanced pseudotargeted analysis using a segment data dependent acquisition strategy by liquid chromatography-tandem mass spectrometry for a metabolomics study of liquiritin in the treatment of depression. J Sep Sci. 2020; 43(11):2088-2096. DOI: 10.1002/jssc.202000107. View

19.

Tao W, Dong Y, Su Q, Wang H, Chen Y, Xue W . Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway. Behav Brain Res. 2016; 308:177-86. DOI: 10.1016/j.bbr.2016.04.039. View

20.

Xie W, Meng X, Zhai Y, Zhou P, Ye T, Wang Z . Panax Notoginseng Saponins: A Review of Its Mechanisms of Antidepressant or Anxiolytic Effects and Network Analysis on Phytochemistry and Pharmacology. Molecules. 2018; 23(4). PMC: 6017639. DOI: 10.3390/molecules23040940. View