[Mechanism of Liangfu Pills in treatment of functional dyspepsia: based on network pharmacology and experimental verification].

This study aims to explore the potential mechanism of Liangfu Pills in the treatment of functional dyspepsia(FD) based on network pharmacology and molecular docking, and verify the mechanism by animal experiment. The active components of Liangfu Pills were screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of Liangfu Pills were predicted by SwissTargetPrediction. The targets of FD were retrieved from GeneCards. On this basis, the common targets of the disease and the pills were yielded and the protein interaction was retrieved based on STRING. The core targets were screened out, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis with DAVID. Finally, molecular docking was carried out with the help of AutoDock Tools to predict the binding degree between the effective components of Liangfu Pills and core targets. A total of 19 active components of Liangfu Pills and 591 FD-related targets were screened out by network pharmacology, of which 253 were common targets of the disease and the prescription. Liangfu Pills was mainly involved in the biological processes of response to drug, negative regulation of transcription, positive regulation of apoptotic process, and cell surface receptor signaling pathway, and the KEGG pathways of hypoxia-inducible factor-1(HIF-1) signaling pathway, serotonergic synapse, tumor necrosis factor(TNF) signaling pathway, cyclic adenosine monophosphate(cAMP) signaling pathway, calcium signal pathway, and inflammatory mediator regulation of transient receptor potential(TRP) channels. The results of molecular docking showed that the key active components of Liangfu Pills had certain binding activity to the targets mitogen-activated protein kinase 1(MAPK1), protein kinase B(AKT1), transient receptor potential cation channel subfamily V member 1(TRPV1), 5-hydroxytryptamine receptor 1 A(HTR1 A), and 5-hydroxytryptamine receptor 2 A(HTR2 A). FD was induced in rats, and then Liangfu Pills was given to FD rats for 7 days. The results showed that Liangfu Pills could significantly relieve the symptoms of FD rats, significantly increase the expression of 5-hydroxytryptamine(5-HT), and down-regulate the expression of TRPV1. Through network pharmacology, molecular docking, and experimental verification, this study proved that Liangfu Pills improved FD through multiple components and multiple targets. The result lays a basis for further research on the mechanism and clinical application of Liangfu Pills in the treatment of FD.

Exercise-induced neuroprotection against cerebral ischemia/reperfusion injury is mediated via alleviating inflammasome-induced pyroptosis.

As a primary nonpharmacological tool, exercise training is neuroprotective after experimental ischemic stroke by relieving neuroinflammation. However, the specific mechanism of which and anti-inflammatory effect of exercise at different intensities require in-depth investigations. To explore the issue, middle cerebral artery occlusion-reperfusion (MCAO-r) in mice were utilized, with subsequent exercise training at different intensities (high-intensity interval training versus moderate-intensity continuous training, i.e. HIIT vs. MICT) during an early phase post-modeling. The neurobehavioral assessment showed that MICT improved the performance of neurological deficit scores and rotarod test earlier, while HIIT appeared to be more efficacious to meliorate locomotor impairments and aerobic fitness at the end of intervention. Both exercise regimens inhibited the expressions of NLRP3 inflammasome components (NLRP3, ASC, and Cl.caspase-1) and pyroptosis-associated proteins (GSDMD, Cl.IL-1ß, and Cl.IL-18) as indicated by western blot and immunofluorescence co-staining. Multiplex assay panel revealed that both exercise regimens reduced the levels of pro-inflammatory cytokines and upregulated anti-inflammatory cytokine. Furthermore, an increased proportion of M2-like microglia and a diminished proportion of M1-like microglia in the peri-infarct zone were observed by colocalization analysis, which was jointly validated by western blot. Here, for the first time, our study demonstrated that HIIT elicited better improvements at functional and cardiovascular levels than MICT after ischemic stroke, and anti-inflammatory effect of exercise might result from suppression in inflammasome-mediated pyroptosis by shifting microglial polarization toward neuroprotective M2 phenotype.