Research Paper Volume 13, Issue 11 pp 15078—15099
Mechanistic insights into the anti-depressant effect of emodin: an integrated systems pharmacology study and experimental validation
- 1 Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Key Laboratory of Neurological Disease of National Education Ministry, Huazhong University of Science and Technology, Wuhan 430030, China
- 2 Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University School of Medicine, Huangshi 435000, China
- 3 Department of Neurology, Shanxian Central Hospital, The Affiliated Huxi Hospital of Jining Medical College, Heze 274300, China
Received: December 11, 2020 Accepted: May 11, 2021 Published: May 29, 2021https://doi.org/10.18632/aging.203072
How to Cite
Copyright: © 2021 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depression is a complex neuropsychiatric disease involved multiple targets and signaling pathways. Systems pharmacology studies could potentially present a comprehensive molecular mechanism to delineate the anti-depressant effect of emodin (EMO). In this study, we investigated the anti-depressant effects of EMO in the chronic unpredictable mild stress (CUMS) rat model of depression and gained insights into the underlying mechanisms using systems pharmacology and molecular simulation analysis. Forty-three potential targets of EMO for treatment of depression were obtained. GO biological process analysis suggested that the biological functions of these targets mainly involve the regulation of reactive oxygen species metabolic process, response to lipopolysaccharide, regulation of inflammatory response, etc. KEGG pathway enrichment analysis showed that the PI3K-Akt signaling pathway, insulin resistance, IL-17 signaling pathway were the most significantly enriched signaling pathways. The molecular docking analysis revealed that EMO might have a strong combination with ESR1, AKT1 and GSK3B. Immunohistochemical staining and Western blotting showed that 2 weeks’ EMO treatment (80 mg/kg/day) reduced depression related microglial activation, neuroinflammation and altered PI3K-Akt signaling pathway. Our findings provide a systemic pharmacology basis for the anti-depressant effects of EMO.
EMO: emodin; CMC-Na: Carboxymethylcellulose sodium; CUMS: chronic unpredictable mild stress; HPA: hypothalamic-pituitary-adrenal; GR: glucocorticoid receptor; BDNF: brain-derived neurotrophic factor; SPT: sucrose preference test; OFT: open field test; FST: forced swimming test; ELISA: the sandwich enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor α; SOD: superoxide dismutase; GSK3β: glycogen synthase kinase 3β; TTD: Therapeutic Target Database; GO: Gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; MCODE: Molecular Complex Detection; PFC: prefrontal cortex.