OBJECTIVE:To elucidate the potential molecular mechanisms of Baishao(Radix Paeoniae Alba)(APR)and Gancao(Radix Glycyrrhizae)(GR)in the treatment of major depressive disorder(MDD).METHODS:Based on the network pharmacol...OBJECTIVE:To elucidate the potential molecular mechanisms of Baishao(Radix Paeoniae Alba)(APR)and Gancao(Radix Glycyrrhizae)(GR)in the treatment of major depressive disorder(MDD).METHODS:Based on the network pharmacology strategy,the therapeutic targets of APR-GR for MDD are predicted,differentially expressed genes from the Integrated Gene Expression database for MDD patients.Topological networks are constructed,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways are enriched,their pharmacological potential molecular mechanisms are discussed,and molecular docking analysis is performed to further motivate compositional and target interactions.Finally,the CUMS mouse model is used for validation.RESULTS:Based on the pharmacological network analysis,17 candidate genes were identified,including muscarinic acetylcholine receptor M1(CHRM1),muscarinic acetylcholine receptor M2(CHRM2),β2-adrenergic receptor(ADRB2),adrenergicα1A receptor(ADRA1A)and 5-hydroxytryptamine transfer protein(SLC6A4),etc.which are primarily involved in reactive oxygen species metabolism,neural response,oxidative stress response and other biological processes.Further analysis revealed that these targets are closely related to Ca^(2+),cyclic adenosine monophosphate,etc.,and exhibit optimal binding sites after molecular docking.Finally,in vivo experiments were performed and it was found that APR-GR significantly improved depression-like behavior and hippocampal impairment in mouse models,increasing brain levels of 5-hydroxytryptamine,dopamine and norepinephrine and decreasing serum levels of corticotropin releasing hormone,corticosterone and adreno cortico tropic hormone,while upregulating the expression of CHRM1,CHRM2 and ADRA1A in the hippocampus and downregulating the expression of SLC6A4 and ADRB2.CNCLUSION:This research sheds light on the potential molecular mechanism of APR-GR to improve MDD.展开更多
OBJECTIVE:To clarify the effect of Hamayou(Oviductus Ranae) protein hydrolysate(ORPH) on depression and its exact underlying mechanism from a new perspective. METHODS:We used the Chronic Unpredictable Mild Stress(CUMS...OBJECTIVE:To clarify the effect of Hamayou(Oviductus Ranae) protein hydrolysate(ORPH) on depression and its exact underlying mechanism from a new perspective. METHODS:We used the Chronic Unpredictable Mild Stress(CUMS) method to prepare a mouse model of depression and lipopolysaccharide(LPS) to prepare a model of BV2 cellular inflammation to investigate the antidepressant effect and mechanism of action of ORPH. Behavioral changes in mice and cerebral blood flow were detected by behavioral experiments and scatter imaging. Levels of corticosterone(CORT), proinflammatory cytokines and neurotransmitter were detected by enzyme-linked immunosorbent assay. Furthermore, hematoxylin-eosin staining, Tunel staining were used to evaluate the effect of ORPH. The distribution and expression of ionized calcium bindingadaptor molecule-1(Iba-1) in mouse hippocampal tissue and BV2 cells were detected by immunofluorescence. Mitogen-activated protein kinase(MAPK) pathway related protein expression was detected by Western blot. RESULTS:ORPH improved depression-like behavior, ameliorated brain tissue damage and apoptosis, and inhibited microglia activation in brain tissue in mice. In addition, ORPH reduced expression of B-cell lymphoma-2(Bcl-2)-associated X(Bax), cysteinyl aspartate specific proteinase 3(Caspase3), cysteinyl aspartate specific proteinase 9(Caspase9), nuclear factor-kappa B(NF-κB), phosphorylation-p38(p-p38), phosphorylation-Jun Nterminal kinase(p-JNK) proteins, and increased expression of Bcl-2, inhibitory kappa B alpha(IκB-α), phosphorylation-extracellular regulated protein kinases 1/2(p-ERK1/2) proteins. On the other hand, there were fewer Iba-1-positive cells, lower expression of NF-κB, pp38, p-JNK and p-ERK1/2 proteins, and higher expression of IκB-α proteins in BV2 cells in the ORPH group. In addition, ORPH increased 5-hydroxytryptamine, norepinephrine levels and decreased CORT, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) levels. CONCLUSION:ORPH was able to improve depressionlike behaviors and that it took effects by promoting cerebral blood flow, inhibition of hypothalamic-pituitaryadrenal axis overactivation, improving the structural damage of hippocampal tissues, and inhibiting the inflammatory response. ORPH can reduced neuronal damage and inhibiting apoptosis by promoting the MAPK pathway.展开更多
基金Supported by Jilin Provincial Department of Science and Technology project:Exploring the Material Basis and Action Pathways of Baihu Tang's Antipyretic Effect based on Omics Technology(20240602036RC)。
文摘OBJECTIVE:To elucidate the potential molecular mechanisms of Baishao(Radix Paeoniae Alba)(APR)and Gancao(Radix Glycyrrhizae)(GR)in the treatment of major depressive disorder(MDD).METHODS:Based on the network pharmacology strategy,the therapeutic targets of APR-GR for MDD are predicted,differentially expressed genes from the Integrated Gene Expression database for MDD patients.Topological networks are constructed,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways are enriched,their pharmacological potential molecular mechanisms are discussed,and molecular docking analysis is performed to further motivate compositional and target interactions.Finally,the CUMS mouse model is used for validation.RESULTS:Based on the pharmacological network analysis,17 candidate genes were identified,including muscarinic acetylcholine receptor M1(CHRM1),muscarinic acetylcholine receptor M2(CHRM2),β2-adrenergic receptor(ADRB2),adrenergicα1A receptor(ADRA1A)and 5-hydroxytryptamine transfer protein(SLC6A4),etc.which are primarily involved in reactive oxygen species metabolism,neural response,oxidative stress response and other biological processes.Further analysis revealed that these targets are closely related to Ca^(2+),cyclic adenosine monophosphate,etc.,and exhibit optimal binding sites after molecular docking.Finally,in vivo experiments were performed and it was found that APR-GR significantly improved depression-like behavior and hippocampal impairment in mouse models,increasing brain levels of 5-hydroxytryptamine,dopamine and norepinephrine and decreasing serum levels of corticotropin releasing hormone,corticosterone and adreno cortico tropic hormone,while upregulating the expression of CHRM1,CHRM2 and ADRA1A in the hippocampus and downregulating the expression of SLC6A4 and ADRB2.CNCLUSION:This research sheds light on the potential molecular mechanism of APR-GR to improve MDD.
基金Science and Technology Development Project of Jilin Province:Preparation and Evaluation of an Animal Model of Liverdepression Type Depression (20220505038ZP)Exploring the Material Basis and Action Pathway of the Antipyretic Effect of Baihu Tang based on Histologic Techniques (20240602036RC)。
文摘OBJECTIVE:To clarify the effect of Hamayou(Oviductus Ranae) protein hydrolysate(ORPH) on depression and its exact underlying mechanism from a new perspective. METHODS:We used the Chronic Unpredictable Mild Stress(CUMS) method to prepare a mouse model of depression and lipopolysaccharide(LPS) to prepare a model of BV2 cellular inflammation to investigate the antidepressant effect and mechanism of action of ORPH. Behavioral changes in mice and cerebral blood flow were detected by behavioral experiments and scatter imaging. Levels of corticosterone(CORT), proinflammatory cytokines and neurotransmitter were detected by enzyme-linked immunosorbent assay. Furthermore, hematoxylin-eosin staining, Tunel staining were used to evaluate the effect of ORPH. The distribution and expression of ionized calcium bindingadaptor molecule-1(Iba-1) in mouse hippocampal tissue and BV2 cells were detected by immunofluorescence. Mitogen-activated protein kinase(MAPK) pathway related protein expression was detected by Western blot. RESULTS:ORPH improved depression-like behavior, ameliorated brain tissue damage and apoptosis, and inhibited microglia activation in brain tissue in mice. In addition, ORPH reduced expression of B-cell lymphoma-2(Bcl-2)-associated X(Bax), cysteinyl aspartate specific proteinase 3(Caspase3), cysteinyl aspartate specific proteinase 9(Caspase9), nuclear factor-kappa B(NF-κB), phosphorylation-p38(p-p38), phosphorylation-Jun Nterminal kinase(p-JNK) proteins, and increased expression of Bcl-2, inhibitory kappa B alpha(IκB-α), phosphorylation-extracellular regulated protein kinases 1/2(p-ERK1/2) proteins. On the other hand, there were fewer Iba-1-positive cells, lower expression of NF-κB, pp38, p-JNK and p-ERK1/2 proteins, and higher expression of IκB-α proteins in BV2 cells in the ORPH group. In addition, ORPH increased 5-hydroxytryptamine, norepinephrine levels and decreased CORT, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) levels. CONCLUSION:ORPH was able to improve depressionlike behaviors and that it took effects by promoting cerebral blood flow, inhibition of hypothalamic-pituitaryadrenal axis overactivation, improving the structural damage of hippocampal tissues, and inhibiting the inflammatory response. ORPH can reduced neuronal damage and inhibiting apoptosis by promoting the MAPK pathway.
