The effects and mechanisms of modified Xiaoyaosan on chronic unpredictable mild stress (CUMS)-induced depressive mice based on network pharmacology.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Clinical research and basic scientific experiments have shown that modified Xiaoyaosan (MXYS) has antidepressant effects, whose system mechanism however has not been thoroughly characterized.

AIM OF THE STUDY:

This research was aimed at evaluating the treatment effects of MXYS on chronic unpredictable mild stress (CUMS)-induced depressive mice and exploring underlying mechanisms.

MATERIALS AND METHODS:

Whether MXYS has effects on depression was investigated via the depressive behaviors of mice, electron microscopy, real-time quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, immunofluorescence (IF) staining and the stereotaxic injection of adeno-associated viruses (AAVs). In addition, network pharmacology was applied to predict relevant molecular targets and possible mechanisms and perform further in vivo validation.

RESULTS:

MXYS is effective in ameliorating the depression-like symptoms of CUMS mice. It can stimulate autophagosome formation, activate the expression of microtubule-associated protein 1 light chain 3 (LC3B), autophagy-related gene 5 (Atg5), Atg7 and neuron-specific nuclear protein (NeuN), and decrease the protein expression sequestosome 1 (SQSTM1/p62). The autophagy-upregulating effect of MXYS was weakened by silencing. The network pharmacology analysis revealed that mitogen-activated protein kinase 1 (MAPK1), MAPK3, serine/threonine-protein kinase (AKT1), proto-oncogene tyrosine-protein kinase (SRC), PI 3 kinase p85 alpha (PIK3R1), catenin (cadherin-associated protein) beta 1 (CTNNB1) and human thrombin activator 1 (HRAS) may be of importance to treat depression by MXYS. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that metabolic and autophagy pathways, pathways in cancer and MAPK, phosphoinositide 3-kinase (PI3K)-Akt and rhoptry-associated protein 1 (Rap1) signaling pathways are involved in the antidepressant effects of MXYS. As suggested by Western blot, the anti-depression mechanism of MXYS is possibly associated with the extracellular signal-regulated protein kinase (ERK)/P38 MAPK signaling pathway.

CONCLUSION:

The findings indicate the possible antidepressant effects of MXYS on CUMS mice via triggering autophagy to alleviate neuronal apoptosis and prompting autophagy, which may involve the ERK/P38 MAPK signaling pathway.

• Authors: Yuan Liu, Dong Guo, Bin Yu, Ting Zeng, Feng-Li Jiao, Yan-Meng Bi
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 324 Pg. 117754 (Apr 24 2024) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 38232859 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• xiaoyaosan
• Phosphatidylinositol 3-Kinases
• Antidepressive Agents
• p38 Mitogen-Activated Protein Kinases
• Proto-Oncogene Proteins c-akt
• Drugs, Chinese Herbal

Topics

• Mice
• Humans
• Animals
• Depression (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Network Pharmacology
• Antidepressive Agents (pharmacology, therapeutic use)
• p38 Mitogen-Activated Protein Kinases
• Proto-Oncogene Proteins c-akt (metabolism)
• Drugs, Chinese Herbal