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Objective To explore the active components, targets and possible mechanism of Yishen Tongluo (Kidney-boosting Collateral-unblocking) Formula (YSTLF) in the treatment of diabetic kidney disease (DKD) based on network pharmacology. Methods The effective components and related targets of YXTLF were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform ( TCMSP), The Encyclopedia of Traditional Chinese Medicine ( ETCM) and A Bioinformatics Analysis Tool for Molecular mechanism of Tradition Chinese Medicine (BATMAN-TCM), and further supplemented with literature research. Then these components and targets were associated with the target information related to DKD in GeneCards, OMIM, TTD and DrugBank databases. Based on the protein-protein interaction (PPI) network constructed by String11. 0 software, the key targets corresponding to the main active components in YSTLF were obtained. The "component-disease-target" regulatory network diagram with TCM compounds was constructed by cytoscape 3. 8. 0, and the pharmacodynamic mechanism of YSTLF in the treatment of DKD was preliminarily predicted. At the same time, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analysis were carried out using R language BioConductor and pathview software to reveal the functions of related target genes and pathways. With the mesangial cells ( SV40-MES-13) of mice induced by high glucose as the main research object, the effects of YSTLF on the expression of key target genes and the regulation of related pathways were verified by luciferase reporter gene detection, RT-qPCR and western blot. Results 108 active components of YSTLF with potential therapeutic effect of DKD and 417 corresponding targets were screened. The " component-disease-target" network diagram suggested that kaempferol and astragaloside were the main active components in YSTLF in the treatment of DKD, and Akt and IL-6 were the key targets of the above-mentioned chemical components. The result of GO functional annotation and KEGG pathway enrichment showed that the selected key targets were mainly involved in a series of biological reactions, such as drug immune response, oxidative stress response, inflammatory response, and signal transduction, etc., and were mainly involved in the regulation of AGE-RAGE and PI3K/ AKT signal pathways. The result showed that YSTLF could effectively improve the activation of inflammation related indexes TNF-α and IL-6 and fibrosis related indexes TGF-β1, α-SMA and Col-I in SV40-MES-13 cells in mice induced by high glucose. Conclusion Yishen Tongluo Formula seems to be multi-component, multi-target and multi-pathway in the treatment of DKD. It may play a role in the treatment of DKD by regulating AGE-RAGE and PI3K/ AKT signal pathways, thus inhibiting inflammatory reaction and renal tissue fibrosis. [ABSTRACT FROM AUTHOR]

The accumulation of iron-dependent lipid peroxides is one of the important causes of NAFLD. The purpose of this study is to explore the effect of dehydroabietic acid (DA) on ferroptosis in nonalcoholic fatty liver disease (NAFLD) mice and its possible mechanisms. DA improved NAFLD and reduced triglycerides (TG), total cholesterol (TC), and lipid peroxidation level and inhibited ferroptosis in the liver of HFD-induced mice. DA binds with Keap1 to form 3 stable hydrogen bonds at VAL512 and LEU557 and increased nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elemen (ARE) luciferase activity. DA promoted the expression downstream of Nrf2 such as heme oxygenase-1 (HO-1), glutathione (GSH) and its peroxidase 4 (GPX4), so as to eliminate the accumulation of reactive oxygen species (ROS) and reduce lipid peroxides malondialdehyde (MDA) in the liver. DA inhibited ferroptosis and increased the expression of key genes such as ferroptosis suppressor protein 1 (FSP1) in vitro and vivo. In all, DA may bind with Keap1, activate Nrf2-ARE, induce its target gene expression, inhibit ROS accumulation and lipid peroxidation, and reduce HFD-induced NAFLD. [ABSTRACT FROM AUTHOR]

A new platform for triptolide (TP) delivery was prepared by conjugating TP to a carboxylmethyl chitosan (CMCS). Compared with the natural TP, the TP-conjugate (TP-CMCS) containing TP of ~5 wt% exhibited excellent aqueous solubility (>5 mg/mL). Results of in vitro experiments showed that TP-CMCS could relieve TP-induced inhibition on RAW264.7 cells and apoptosis, respectively. Compared with the TP group, TP-CMCS could effectively alleviate the toxicity injury of TP and decreased the mortality rate of the mice (p < 0.05). TP-CMCS did not cause much damage to the liver (AST and ALT) and kidney (BUN and CRE) (p < 0.05). After administration, the levels of IL-6, IL-1β, and TNF-α decreased, and the arthritis detumescence percentages increased significantly, and the bony erosion degree was distinctly decreased in the TP-CMCS groups and TP group. Our results suggested that TP-CMCS was a useful carrier for the treatment of RA, which enhanced aqueous solubility of free TP and reduced drug toxicity in vitro and in vivo. [ABSTRACT FROM AUTHOR]

A method based on enzyme blocking combined with ultrafiltration liquid chromatography–mass spectrometry (LC–MS) has been developed to identify xanthine oxidase (XOD) inhibitors in the roots of Lindera reflexa Hemsl (LR) and determine their binding positions. Allopurinol and febuxostat, known XOD inhibitors, which occupy different binding positions in XOD, were used as blockers and pre‐incubated with XOD. Then the LR extract was incubated without XOD, and with XOD, allopurinol‐blocked XOD and febuxostat‐blocked XOD before ultrafiltration LC–MS was performed. By comparing the chromatographic profiles of the incubation samples, not only the ligands, but also the binding position of these ligands with XOD could be determined. Finally, three compounds, pinosylvin, pinocembrin and methoxy‐5‐hydroxy‐trans‐stilbene, were identified as potential XOD inhibitors and the binding modes of these three compounds were shown to be similar to those of febuxostat. To verify the XOD inhibitory activity of the screened compounds, the microplate method and molecular docking in silico were used to evaluate the enzyme inhibitory activities and the binding positions with XOD. The results showed that the developed method could screen for XOD ligands in LR extracts and also determine the binding positions of the ligands. To our knowledge, this is the first report of the XOD inhibitory activity of these three compounds. [ABSTRACT FROM AUTHOR]