ABSTRACT
Two undescribed sesquiterpenoids, including one nor-eudesmane type (1) and one guaiane type (2), together with two known analogues (3-4) have been isolated and identified from the fruits of Alpinia oxyphylla. The structures of these new compounds were elucidated by extensive spectroscopic analyses (1D-, 2D-NMR, HRESIMS, IR, UV) and NMR calculations with DP4+ analysis. The anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on PGE2 production in LPS stimulated RAW 264.7 macrophages.
ABSTRACT
BACKGROUND: The Yixiang capsule with traditional Chinese herbs Cistanches Herba, Hedysarum multijugum Maxim,Fructus Ligustri Lucidi,and Fructus lycii are the main raw materials in a modern herbal medicine preparation containing corresponding bioactive ingredients after extraction and processing. This study aimed to investigate the immune-enhancing function of the Yixiang capsule and explore its potential mechanism. METHODS: After oral administration of the Yixiang capsule to mice for 30 days, the spleen lymphocyte transformation activity, NK cell activity, DTH, macrophage phagocytosis, HC50 value, amounts of antibody-producing cells, carbon particle clearance rate, spleen, and thymus index were determined to evaluate the regulation effect of the Yixiang capsule on immune function. The potential mechanism underlying the immune-enhancing function of the Yixiang capsule was studied based on network pharmacology and molecular docking. RESULTS: The results showed that the Yixiang capsules can obviously increase the HC50 values in all groups, significantly enhance the DTH reaction of mice, the carbon clearance function in medium and high dose groups,and the phagocytic function of macrophages in high dose groups, but had no significant effect on NK cell activity, T lymphocyte proliferation, body weight and immune organ weight of mice. A total of 78 compounds of the Yixiang capsule may affect 123 metabolic pathways and 1022 GO terms by regulating 232 targets, such as the cancer signaling pathway ad the signal pathways of response to lipopolysaccharide, and the key targets predicted could stably bind to the core active components of the Yixiang capsule. CONCLUSION: These results suggested that the Yixiang capsule could enhance the immune function of mice and have the characteristics of a multi-component and multi-target synergistic effect on the enhanced immunity function, which provides the basis for the follow-up study.
ABSTRACT
Ginkgo biloba L. leaves (GBLs), as widely used plant extract sources, significantly improve cognitive, learning and memory function in patients with dementia. However, few studies have been conducted on the specific mechanism of Neurodegenerative diseases (NDs). In this study, network pharmacology was employed to elucidate potential mechanism of GBLs in the treatment of NDs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the chemical components in accordance with the screening principles of oral availability and drug-like property. Potential targets of GBLs were integrated with disease targets, and intersection targets were exactly the potential action targets of GBLs for treating NDs; these key targets were enriched and analyzed by the protein protein interaction (PPI) analysis and molecular docking verification. Key genes were ultimately used to find the biological pathway and explain the therapeutic mechanism by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Twenty-seven active components of GBLs may affect biological processes such as oxidative reactions and activate transcription factor activities. These components may also affect 120 metabolic pathways, such as the PI3K/AKT pathway, by regulating 147 targets, including AKT1, ALB, HSP90AA1, PTGS2, MMP9, EGFR and APP. By using the software iGEMDOCK, the main target proteins were found to bind well to the main active components of GBLs. GBLs have the characteristics of multi-component and multi-target synergistic effect on the treatment of NDs, which preliminarily predicted its possible molecular mechanism of action, and provided the basis for the follow-up study.
Subject(s)
Drugs, Chinese Herbal/chemistry , Ginkgo biloba/chemistry , Neurodegenerative Diseases/drug therapy , Nootropic Agents/chemistry , Plant Leaves/chemistry , Databases, Pharmaceutical , Drugs, Chinese Herbal/metabolism , Gene Ontology , Humans , Molecular Docking Simulation , Nootropic Agents/metabolism , Pharmacology/methods , Protein Binding , Protein Interaction Maps , Proteins/metabolismABSTRACT
Netrin-1 is best known for its function guiding axon growth and migration. Netrin-1 has been shown to be involved in regulating cardiovascular function. In this study, we aimed to understand the biological role of Netrin-1 and its receptor Unc5b in endothelial cells. Our results demonstrate that Unc5b was moderately expressed in human aortic endothelial cells (HAECs) and TNF-α had a dose-dependent inhibitory effect on Unc5b level. Netrin-1 potently suppressed TNF-α-induced vascular adhesion molecules VCAM-1, ICAM-1, E-selectin and blocked the adhesion of monocytes to endothelial cells. Netrin-1 also suppressed TNF-α-induced production of cytokines including MCP-1, IL-1ß, and IL-6. Importantly, Netrin-1 suppressed toll like receptor 4 (TLR4) expression and prevented NF-κB activation. Mechanistically, Netrin-1 reduced TNF-α-induced IKK and IκBα activation and prevented degradation of IκBα. Netrin-1 reduced nuclear accumulation of p65 and strongly suppressed NF-κB promoter activation. Collectively, our data demonstrated that signaling of Netrin-1 and its receptor Unc5b had an anti-inflammatory effect in endothelial cells. Netrin-1 signaling could be imperative for normal endothelial function.
Subject(s)
Cytokines/immunology , Endothelial Cells/drug effects , Inflammation Mediators/immunology , Monocytes/immunology , Netrin-1/pharmacology , Cell Adhesion/drug effects , Cell Adhesion/genetics , Cell Adhesion/immunology , Cytokines/genetics , Cytokines/metabolism , Endothelial Cells/immunology , Endothelial Cells/metabolism , Gene Expression/drug effects , Gene Expression/immunology , Humans , Inflammation Mediators/metabolism , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/immunology , Intercellular Adhesion Molecule-1/metabolism , Monocytes/cytology , Monocytes/metabolism , Netrin Receptors , Protective Agents/pharmacology , Receptors, Cell Surface/genetics , Receptors, Cell Surface/immunology , Receptors, Cell Surface/metabolism , Signal Transduction/drug effects , Signal Transduction/genetics , THP-1 Cells , Tumor Necrosis Factor-alpha/pharmacology , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/immunology , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
In order to effectively remove the invalid impurities in Tongan injection, optimize the optimal parameters of the impurity removal technology of liquid mixing process, in this paper, taking Tongan injection as the research object, with the contents of celandine alkali, and sinomenine, solids reduction efficiency, and related substances inspection as the evaluation indexes, the removal of impurities and related substances by the combined process of refrigeration, coction and activated carbon adsorption were investigated, the feasibility of the impurity removal method was definited and the process parameters were optimized. The optimized process parameters were as follows: refrigerated for 36 h, boiled for 15 min, activated carbon dosage of 0.3%, temperature 100 degrees C, adsorption time 10 min. It can effectively remove the tannin, and other impurities, thus ensure the quality and safety of products.
