ABSTRACT
Aim To confirm the antidepressant effect of the volatile oil part of the disassembled prescription drugs (Chai Hu, Dang Gui and Bo He, referred to as CDB) from Xiaoyao Powder and investigate its mechanism via Nrf2/H0-1 signaling pathway on OB model rats. Methods GC-MS analysis of the main components of volatile oil part of CDB was performed. The rats were randomly divided into sham operation group, model group, fluoxetine hydrochloride group (FLX, 10 mg • kg
ABSTRACT
This paper aimed to explore the antidepressant effect of the essential oil from Schizonepeta tenuifolia Briq.(EOST) on the treatment of depression and its mechanism by using a combination of network pharmacology and the mouse model of lipopolysaccharide(LPS)-induced depression. The chemical components in EOST were identified using gas chromatography-mass spectrometer(GC-MS), and 12 active components were selected as the study objects. The targets related to EOST were obtained by Traditional Chinese Medicines Systems Pharmacology(TCMSP) and SwissTargetPrediction database. The targets related to depression were screened out through GeneCards, Therapeutic Target Database(TTD), and Online Mendelian Inheritance in Man(OMIM) database. The Venny 2.1 was applied to screen out the common targets of EOST and depression. The targets were imported into Cytoscape 3.7.2 to generate "drug-active component-diease-target" network diagram. The protein-protein interaction(PPI) network was constructed using STRING 11.5 database and Cytoscape 3.7.2, and the core targets were screened out. DAVID 6.8 database was used for Gene Ontology(GO) func-tional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and subsequently the enrichment results were visualized through the bioinformatics platform. The mouse model of depression was induced by intraperitoneally injecting with LPS in mice. Before modeling, mice were administrated orally with EOST. The antidepressant effect of EOST was evalua-ted by tail suspension test(TST), forced swimming test(FST), and novelty suppressed feeding test(NSFT) after modeling. The content of interleukin(IL)-1β was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression levels of IL-1β and pro IL-1β in the hippocampus were determined by Western blot. There were 12 main components and 179 targets in EOAT, of which, 116 targets were related to depression, mainly involved in neuroactive ligand-receptor interaction, calcium signaling pathway, and cyclic adenosine monophosphate(cAMP) signaling pathway. Biological processes such as synaptic signal transduction, G-protein coupled receptor signaling pathway, and chemical synaptic transmission were involved. Molecular functions such as neurotransmitter receptor activity, RNA polymerase Ⅱ transcription factor activity, and heme binding were involved. In mice experiments, the results showed that EOST at 100 mg·kg~(-1) and 50 mg·kg~(-1) significantly shortened the immobility time in TST and FST as well as the feeding latency in NSFT compared with the model group, decreased the levels of serum IL-1β and NO, and reduced the protein expression levels of IL-1β and pro IL-1β in the hippocampus. In conclusion, EOST shows a good antidepressant effect in a multi-component, multi-target, and multi-pathway manner. The mechanism may be attributed to the fact that EOST can down-regulate the protein expression levels of IL-1β and pro IL-1β, decrease the release of inflammatory factors, and reduce neuroinflammation response.
Subject(s)
Animals , Mice , Oils, Volatile , Depression , Lipopolysaccharides , Network Pharmacology , Databases, Genetic , Calcium Signaling , Disease Models, AnimalABSTRACT
Pyroptosis is a programmed cell death initiated by the activation of caspases, which is involved in the development and progression of several cardiovascular diseases. The gasdermins, a protein family, are key executive proteins in the development of pyroptosis, which increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate the inflammatory injury. Traditional Chinese medicine(TCM)has shown unique therapeutic advantages in cardiovascular diseases with multi-component and multi-target characteristics. Currently, the effective prevention and treatment of cardiovascular diseases based on the theory of pyroptosis become a new research hotspot in this field. Based on the theories of TCM and modern medicine, this study summarized the role of pyroptosis in cardiovascular diseases such as atherosclerosis, myocardial infarction, diabetic cardiomyopathy, hypertension, and myocarditis. The role of TCM, including active monomers, crude extracts, and compound preparations, in cardiovascular protection through the regulation of pyroptosis was also summarized, providing a theoretical basis for the clinical prevention and treatment of cardiovascular diseases by TCM.
Subject(s)
Humans , Medicine, Chinese Traditional , Drugs, Chinese Herbal/therapeutic use , Cardiovascular Diseases/prevention & control , Pyroptosis , Myocardial Infarction/drug therapyABSTRACT
Objective:To investigate the intervention effect of <italic>n</italic>-butyl alcohol extracts from Xiaoyaosan against depression-like behavior induced by chronic unpredictable mild stress (CUMS) in model mice and the role of insulin-like growth factor-1 receptor <italic>β</italic> (IGF-1R<italic>β</italic>)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathway in such intervention. Method:The effective dose of n-butyl alcohol extracts from Xiaoyaosan was preliminarily determined in model mice with behavioral despair. Then the male C57BL/6 mice were randomly divided into the blank group, model group, fluoxetine group, Xiaoyaosan group, and the low- (20 g·kg<sup>-1</sup>) and high-dose (40 g·kg<sup>-1</sup>) <italic>n</italic>-butyl alcohol extract groups. The mice in all groups except for the blank group were exposed to CUMS for inducing the depression-like behavior, which was judged by the sucrose preference test (SPT). The successfully modeled mice in the medication groups were intragastrically administered with the corresponding drugs, whereas those in the blank and model groups were treated with an equal volume of solvent for five successive weeks. Following the SPT, tail suspension test (TST), and novelty suppressed feeding test (NSFT) at the end of the fifth week, the insulin-like growth factor-1 (IGF-1) levels in mouse serum and hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The average optical density (<italic>IA</italic>) of Nissl bodies in mouse hippocampal CA3 region was detected by toluidine blue staining. The 5-bromo-2-deoxyuridine (Brdu) and doublecortin (DCX) expression in the dentate gyrus (DG) was assayed using immunofluorescence method. The protein expression levels of IGF-1R<italic>β</italic>, PI3K, phosphorylated-PI3K (p-PI3K), Akt, p-Akt, cysteine aspartic acid-specific protease 3 (Caspase-3), and cleaved Caspase-3 in the hippocampus were determined by Western blot. Result:The results of forced swimming test and TST showed that n-butyl alcohol extracts from Xiaoyaosan at 9.1 and 40 g·kg<sup>-1</sup> both significantly shortened the immobility time of mice (<italic>P</italic><0.05, <italic>P</italic><0.01), indicating that the effective dose ranged from 9.1-40 g·kg<sup>-1</sup>. Compared with the model control, the n-butyl alcohol extracts from Xiaoyaosan at 20 and 40 g·kg<sup>-1</sup> significantly increased the sucrose preference percentage (<italic>P</italic><0.05, <italic>P</italic><0.01), shortened the immobility time in TST (<italic>P</italic><0.01) and the feeding latency in NSFT (<italic>P</italic><0.01), reversed the down-regulated IGF-1 content in mouse serum and hippocampus (<italic>P</italic><0.01), increased the AOD of Nissl bodies in the hippocampal CA3 region (<italic>P</italic><0.01), promoted the expression of Brdu and DCX in DG (<italic>P</italic><0.05, <italic>P</italic><0.01), and down-regulated the protein expression levels of IGF-1R<italic>β</italic> (<italic>P</italic><0.05, <italic>P</italic><0.01), p-PI3K/PI3K (<italic>P</italic><0.05, <italic>P</italic><0.01), p-Akt/Akt (<italic>P</italic><0.05), and cleaved Caspase-3/Caspase-3 in the hippocampus of CUMS mice. Conclusion:The n-butyl alcohol extracts from Xiaoyaosan are equivalent to Xiaoyaosan in inhibiting expression. They alleviate the depression-like behavior in CUMS mice, induce the production of Nissl bodies in hippocampal CA3 region, enhance neuronal proliferation and differentiation in DG, and facilitate neurogenesis. All these may be related to the inhibition of over-activated IGF-1R<italic>β</italic>/PI3K/Akt pathway and the reduction of neuronal apoptosis.
ABSTRACT
Objective Hemocoagulase injection based on the venom of is widely used in the treatment of hemorrhagic disorders. This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection.Methods We retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1, 2015 to March 31, 2018. Clinical data were collected and investigated, including clinical manifestations, hemostatic and fibrinolytic parameters, dosage of hemocoagulase, the medication time, and the cryoprecipitate blood product infusion. Differences in fibrinogen, D-dimer, and fibrin/fibrinogen degradation products (FDP) before, during, and after the application of hemocoagulase injection were analyzed statistically.Results Plasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment (=1.80, <0.001), with the average decrease of 2.28 g/L (0.63-3.9 g/L). After withdrawal, fibrinogen level increased significantly compared to that during the medication (=-1.20, <0.001), but was still lower than that before the medication (=0.59, =0.03). The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication (=0.83, =0.002; Wilcoxon-test, =-4.54, <0.001). Spearman's correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemocoagulase (=-0.17, =0.40; =-0.28, =0.15; respectively) and the time of recovery from hypofibrinogenemia (=-0.45, =0.05; =0.13, =0.61; respectively).Conclusion Monitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection. Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.