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Objective. This study aimed to clarify the mechanism of Fei-Xian formula (FXF) in the treatment of pulmonary fibrosis based on network pharmacology analysis combined with molecular docking validation. Methods. Firstly, ingredients in FXF with pharmacological activities, together with specific targets, were identified based on the BATMA-TCM and TCMSP databases. Then, targets associated with pulmonary fibrosis, which included pathogenic targets as well as those known therapeutic targets, were screened against the CTD, TTD, GeneCards, and DisGeNet databases. Later, Cytoscape was employed to construct a candidate component-target network of FXF for treating pulmonary fibrosis. In addition, for nodes within the as-constructed network, topological parameters were calculated using CytoHubba plug-in, and the degree value (twice as high as the median degree value for all the nodes) was adopted to select core components as well as core targets of FXF for treating pulmonary fibrosis, which were subsequently utilized for constructing the core network. Furthermore, molecular docking study was carried out on those core active ingredients together with the core targets using AutoDock Vina for verifying results of network pharmacology analysis. At last, OmicShare was employed for enrichment analysis of the core targets. Results. Altogether 12 active ingredients along with 13 core targets were identified from our constructed core component-target network of FXF for the treatment of pulmonary fibrosis. As revealed by enrichment analysis, the 13 core targets mostly concentrated in regulating biological functions, like response to external stimulus (from oxidative stress, radiation, UV, chemical substances, and virus infection), apoptosis, cell cycle, aging, immune process, and protein metabolism. In addition, several pathways, like IL-17, AGE-RAGE, TNF, HIF-1, PI3K-AKT, NOD-like receptor, T/B cell receptor, and virus infection-related pathways, exerted vital parts in FXF in the treatment of pulmonary fibrosis. Conclusions. FXF can treat pulmonary fibrosis through a "multicomponent, multitarget, and multipathway" mean. Findings in this work lay foundation for further exploration of the FXF mechanism in the treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) causes heart failure and increases the mortality in diabetic patients. Myocardial apoptosis and fibrosis are the main features of DCM and aging. The aim is to study the underlying mechanism of D-pinitol (DP) on myocardial apoptosis and fibrosis in an elderly diabetic mouse model. The diabetic model was established by SAMP-8 mice that were injected with streptozotocin daily for five consecutive days. The mice were administrated of DP (150 mg kg-1 day-1) by gavage for 10 weeks. The common metabolic disorder indices, cardiac dysfunction, oxidative stress, myocardial apoptosis and fibrosis, and PI3K/Akt/mTOR pathway were investigated. Our findings suggested that DP has a protective effect on DCM, which may be related to regulating oxidative stress, and PI3K/Akt/mTOR pathway involving cardiac fibrosis and apoptosis. DP may be a novel clinical application in fighting against DCM. Practical applications: D-pinitol (DP) was found in large quantities in soybean and legume foods. DP has a variety of functions, including hypoglycemic, anti-oxidation, anti-inflammatory, cardioprotective, and anti-tumor activity. We used the streptozotocin-induced SAMP8 mice as the diabetic model and treated with DP. We found that DP can improve cardiac dysfunction and inhibits the oxidative stress, myocardial apoptosis and fibrosis. DP has a significant effect on diabetic cardiomyopathy (DCM). The molecular mechanisms are related to regulating oxidative stress, and PI3K/Akt/mTOR pathway involving cardiac fibrosis and apoptosis. DP can prevent and/or delay the onset of DCM. [ABSTRACT FROM AUTHOR]

To investigate the effect of intermittent high glucose (IHG) and sustained high glucose (SHG) on inducing β-cell apoptosis and the potential involved mechanisms, INS-1 beta cells were incubated for 72 h in the medium containing different glucose concentrations: control (5.5mmol/L), SHG (33.3mmol/L), and IHG (5.5mmol/L and 33.3mmol/L glucose alternating every 12 h). Cell viability, apoptosis rate, and oxidative-stress markers were determined. The results showed that the apoptosis induced by IHG was more obvious than that by SHG. Simultaneously, the intracellular level of oxidative stress was more significantly increased in INS-1 cells exposed to IHG. These findings suggest that intermittent high glucose could be more deleterious to β-cell than a constant high concentration of glucose, this may be due to the aggravation of oxidative stress triggered by intermittent high glucose. [ABSTRACT FROM AUTHOR]