Mechanistic insights into the anti-depressant effect of emodin: an integrated systems pharmacology study and experimental validation

Citations Over Time

Abstract

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.

Related Papers

• → Effect of sample preparation on components and liver toxicity of Polygonum multiflorum(2015)53 cited
• → Pharmacokinetic studies unveiled the drug–drug interaction between trans-2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucopyranoside and emodin that may contribute to the idiosyncratic hepatotoxicity of Polygoni Multiflori Radix(2018)37 cited
• Optimization of extract conditions for emodin from Chinese rhubarb(2010)
• Study on the extraction methods of emodin from Radix polygoni multiflori(2004)
• → Effect of different proportions of piper chinaroot and rhubarb on the dissolution rate of five effective components in rhubarb(2019)