OBJECTIVE:To decipher the antidepressant targets and mechanisms of Huangqin(Radix Scutellariae Baicalensis)(RSB)by a novel computational system based on prediction and experimental verification.METHODS:The putative ta...OBJECTIVE:To decipher the antidepressant targets and mechanisms of Huangqin(Radix Scutellariae Baicalensis)(RSB)by a novel computational system based on prediction and experimental verification.METHODS:The putative targets of RSB against depression were identified from Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Drug Bank.Next,protein-protein interaction network of the anti-depression targets of RSB were identified,and differentially expressed genes(DEGs)of depression were mined from the NCBI database.Then,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were used to analysis the common targets.Finally,the selected pathways and functions were verified by experimentation.RESULTS:Thirty active compounds in RSB were predicted with high confidence by TCMSP and DrugBank,and seventy-one DEGs were identified in the GEO database.Besides,eight core target proteins were screened out by descending order of degree value,including ACHE,IL6,SLC6A4,FOS,SLC6A3,MAOB,DPP4,and JUN.These target genes were further found to be associated with pathways involved in neuronal apoptosis,such as pathways in cancer,Toll-like receptor signaling pathway,and TNF signaling.The cell proliferation assay and wound-healing assay results showed that RSB does not affect PC12 cell proliferation and chemotaxis.Unexpectedly,RSB protected PC12 cells from oxidative stress induced by H2O2 via inhibiting autophagy and apoptosis.We revealed significant changes in mice treated with 400 mg/kg RSB compared with the lipopolysaccharide mice.The possible mechanism for the antidepressive action of RSB is by reducing the expression of LC3-B in CA1 neurons.CONCLUSIONS:Our research partially expounds the mechanism of the antidepressant effect of RSB by the combination of network pharmacology prediction and experimental verification.Furthermore,it is also conducive to the application of Traditional Chinese Medicine within modern medicine.展开更多
基金Supported by Scientific research project of TCM administration of Hebei province:Based on AC-c AMP-PKA-CREB-BDNF Pathway to Explore the Anti-Epilepsy and Improving Learning and Memory Mechanism of Turbid and Detoxifying Prescriptions(No.2020176)National key research and development projects:Demonstration Study on Large-Scale Cultivation and Targeted Poverty Alleviation of High-Quality Genuine Medicinal Materials Forsythia Suspensa,Sour Jujube and Scutellaria in Taihang Mountain-Collection,Evaluation and Screening of Germplasm Resources of Forsythia Suspensa,Sour Jujube and Huangqin(Radix Scutellariae Baicalensis)(No.2017YFC1701700)the Postgraduate Innovation Funding Project of Hebei University of Chinese Medicine:Study on the Mechanism of Huazhuo Jiedu Shugan Prescription Regulating the Cerebral Interstitial Fluid Microenvironment on the Occurrence and Behavioral Changes of Epilepsy(No.XCXZZBS2021016)。
文摘OBJECTIVE:To decipher the antidepressant targets and mechanisms of Huangqin(Radix Scutellariae Baicalensis)(RSB)by a novel computational system based on prediction and experimental verification.METHODS:The putative targets of RSB against depression were identified from Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Drug Bank.Next,protein-protein interaction network of the anti-depression targets of RSB were identified,and differentially expressed genes(DEGs)of depression were mined from the NCBI database.Then,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology were used to analysis the common targets.Finally,the selected pathways and functions were verified by experimentation.RESULTS:Thirty active compounds in RSB were predicted with high confidence by TCMSP and DrugBank,and seventy-one DEGs were identified in the GEO database.Besides,eight core target proteins were screened out by descending order of degree value,including ACHE,IL6,SLC6A4,FOS,SLC6A3,MAOB,DPP4,and JUN.These target genes were further found to be associated with pathways involved in neuronal apoptosis,such as pathways in cancer,Toll-like receptor signaling pathway,and TNF signaling.The cell proliferation assay and wound-healing assay results showed that RSB does not affect PC12 cell proliferation and chemotaxis.Unexpectedly,RSB protected PC12 cells from oxidative stress induced by H2O2 via inhibiting autophagy and apoptosis.We revealed significant changes in mice treated with 400 mg/kg RSB compared with the lipopolysaccharide mice.The possible mechanism for the antidepressive action of RSB is by reducing the expression of LC3-B in CA1 neurons.CONCLUSIONS:Our research partially expounds the mechanism of the antidepressant effect of RSB by the combination of network pharmacology prediction and experimental verification.Furthermore,it is also conducive to the application of Traditional Chinese Medicine within modern medicine.
