ABSTRACT
To investigate the therapeutic effect and molecular mechanism of the main flavonoid components of Silybum marianum (S. marianum) on nonalcoholic fatty liver disease (NAFLD), we identified nine flavonoids in S. marianum through TCMSP, PubChem database and corresponding literatures. The potential therapeutic targets of NAFLD were predicted by SwissTargetPrediction, GeneCards and Venny 2.1.0 platform, while the protein-protein interaction (PPI) network of potential targets was analyzed using String platform and Cytoscape software. Then GO and KEGG pathway enrichment analysis were performed using David 6.8 database, followed by molecular docking verification using AutoDock software. In vitro, components with higher degree value in the "components-targets-pathway" network were chosen for further analysis. L02 cells were used to establish lipid accumulation model and treated with different components. Furthermore, the effects of four pure active compounds from S. marianum on lipid accumulation in hepatocytes were analyzed by oil red O staining. The results showed that the main nine flavonoids extracted from S. marianum contained 24 potential NAFLD targets. Several critical pathways closely related to NAFLD process were identified by GO and KEGG enrichment analysis, including phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, type 2 diabetes pathway, tumor necrosis factor (TNF) pathway and insulin resistance pathway. The results of molecular docking further indicated that the core components displayed strong binding abilities with key targets respectively, and silandrin showed better binding activity as compared to other components. The results obtained from L02 cells showed that the lipid accumulation was reduced by treatment with isosilybin A, isosilybin B, silydianin and silychristin, while the activity of isosilybin B was better than that of isosilybin A. Taken together, we concluded that the main flavone components of S. marianum could improve lipid accumulation through multiple signaling pathway in hepatocytes, and this could be a potential new strategy for the treatment of NAFLD.
ABSTRACT
Seven main components in eleutheroside were used as research objects, and the mechanism of action of total eleutheroside for treatment of diabetes mellitus type 2 was investigated by network pharmacology. The SwissTargetPrediction, GeneCard, and String platforms were used to predict the 35 potential targets of these 7 components that are related to diabetes mellitus type 2. Then we used cytoscape 3.6.1 to build a "component-target" network map and used the Networkanalyzer tool for topology analysis. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis were performed on the DAVID6.8 platform, and the "component-target-path" network map was constructed based on the enrichment results. Those components mainly used in diabetes mellitus type 2 were screened as core components, and the core components were docked with key disease target proteins to verify the potential mechanism of the total eleutheroside. After screening, 8 important pathways associated with diabetes mellitus type 2 were identified. This study showed that eleutheroside A, eleutheroside D, eleutheroside E and sesamin played key roles in insulin resistance, apoptosis and inflammation pathways. The total eleutheroside may ameliorate type 2 diabetes mainly through regulating signal transducer and activator of transcription factors (STATs), non-receptor protein tyrosine phosphatase (PTPN) 1, PTPN2, c-Jun N-terminal kinase (JNK), and p38 mitogen activate protein kinase. These components worked together through multiple signaling pathway. Based on our data, eleutheroside is proposed as a novel therapeutic strategy for treatment of type 2 diabetes.
ABSTRACT
The effects of magnolol (Mag) on hyperglycemia and hyperlipemia, hepatic oxidative stress and cytochrome P4502E1 (CYP2E1) activity of diabetic rats induced by high-fat diet (HFD) and streptozotocin (STZ) were studied. After oral administration of Mag (25, 50 and 100 mg x kg(-1) x d(-1)) for continuous 10 weeks, the blood glucose and lipids (TC, TG and LDL-C) levels, as well as the hepatic CYP2E1 activity and MDA content of diabetic rats, decreased significantly (P < 0.05 or P < 0.01), whereas the oral glucose tolerance and hepatic antioxidant enzymatic activities (CAT and GSH-Px) of diabetic rats, increased significantly (P < 0.05 or P < 0.01). The results indicated that Mag was effective against the hepatic oxidative damage, hyperglycemia and hyperlipemia of diabetic rats induced by HFD and STZ, and the inhibition of Mag on hepatic CYP2E1 activity could be an important mechanism of Mag against hepatic insulin resistance and oxidative damage.