Intestinal macrophages are the main participants of intestinal immune homeostasis and intestinal inflammation. Under different environmental stimuli, intestinal macrophages can be polarized into classical activated pro-inflammatory phenotype (M1) and alternative activated anti-inflammatory phenotype (M2). Its different polarization state is the “guide” to promoting the development and regression of inflammation. Under normal circumstances, intestinal macrophages can protect the intestine from inflammatory damage. However, under the influence of some genetic and environmental factors, the polarization imbalance of intestinal M1/M2 macrophages will lead to the imbalance in the regulation of intestinal inflammation and transform the physiological inflammatory response into pathological intestinal injury. In UC patients, the disorder of intestinal inflammation is closely related to the imbalance of intestinal M1/M2 macrophage polarization. Therefore, restoring the balance of M1/M2 macrophage polarization may be a potentially valuable therapeutic strategy for UC. Evidence has shown that traditional Chinese medicine (TCM) has positive therapeutic effects on UC by restoring the balance of M1/M2 macrophage polarization. This review summarizes the clinical evidence of TCM for UC, the vital role of macrophage polarization in the pathophysiology of UC, and the potential mechanism of TCM regulating macrophage polarization in the treatment of UC. We hope this review may provide some new enlightenment for the clinical treatment, fundamental research, and research and development of new Chinese medicine of UC.
Tangzhiqing formula (TZQ) is a traditional Chinese medicine prescribed to treat glucose and lipid metabolism disorders. A significant effect of TZQ on diabetes and hyperlipidemia has been demonstrated, but its effect on atherosclerosis (AS) remains unknown. This study combines pyroptosis with metabolomics to elucidate the effect and mechanism of TZQ on AS. A model of AS was developed using ApoE−/− mice fed a high-fat diet for 8 weeks. After 6 weeks of atorvastatin (Ator) or TZQ treatment, aortic lumen diameter, aortic lesion size, serum lipid profile, cytokines, and Nod-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis were analyzed. Serum metabolomics profiles were obtained to examine the effect of TZQ on AS and the correlation between pyroptosis and metabolites was further analyzed. As a result, TZQ significantly reduced the diameter of the common carotid artery during diastole and the blood flow velocity in the aorta during systole; reduced blood lipid levels, arterial vascular plaques, and the release of inflammatory cytokines; and inhibited the NLRP3 inflammasome-mediated pyroptosis. According to metabolomics profiling, TZQ is engaged in the treatment of AS via altering arachidonic acid metabolism, glycerophospholipid metabolism, steroid hormone production, and unsaturated fatty acid biosynthesis. The cytochrome P450 enzyme family and cyclooxygenase 2 (COX-2) are two major metabolic enzymes associated with pyroptosis.
Background
Qinggong Shoutao Pill (QGSTW) is extensively used as a traditional medicine to prevent and treat age-associated memory decline. However, its potential therapeutic mechanisms and targets are unclear.
Methods
Network pharmacology and molecular Docking approach was utilized to identified the main active components of QGSTW, the potential pathway and target of QGSTW effect on memory decline. Age-associated memory impairment of mouse model induced by D-galactose was established to verified the pathway and target of QGSTW effectiveness on memory decline, as shown by behavioral tests, immunofluorescence staining and western blot.
Results
By retrieving, 206 chemical components were identified in QGSTW. Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in neuroactive ligand-receptor interaction, cAMP signaling pathway and calcium signaling pathway, which were closely related with signal transduction and chemical synaptic transmission. The interrelationships between common targets were analyzed by PPI network and ten biomarkers were discovered. Ten QGSTW active components were revealed furtherly. The affinity between the top five targets and their corresponding active ingredients was predicted by molecular docking. Finally, experiments showed that QGSTW could upregulate the expression of cAMP signaling pathway related targets PKA, CREB, and synaptic plasticity related proteins GluN1, GluA1, CaMKⅡ-α, c-Fos and SYN, contributing to the recovery of memory decline in D-galactose-injured mice.
Conclusions
This paper revealed the key nodes of QGSTW effect on anti-memory decline are cAMP signaling pathway and synaptic plasticity.
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