Targeting dendritic cells (DCs) metabolism-related pathways and in-situ activation of DCs have become a new trend in DC-based immunotherapy. Studies have shown that Lycium barbarum polysaccharide can promote DCs function. This study is aimed at exploring the mechanism of LBP affecting DCs function from the perspective of metabolomics. MTT method was used to detect the activity of DC2.4 cells. ELISA kit method was used to detect the contents of IL-6, IL-12, and TNF-α in the supernatant of cells. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to detect general changes in DC2.4 cell metabolism. And then multidistance covariates and bioinformatics, partial least squares-discriminant analysis (PLS-DA) were used to analyze differential metabolites. Finally, metabolic pathway analysis was performed by MetaboAnalyst v5.0. The results showed that LBP had no significant inhibitory effect on the activity of DC2.4 cells at the experimental dose of 50-200 μg/ml. LBP (100 μg/ml) could significantly stimulate DC2.4 cells to secrete IL-6, TNF-α, and IL-12. Moreover, 20 differential metabolites could be identified, including betaine, hypoxanthine, L-carnitine, 5’-methylthioadenosine, orotic acid, sphingomyelin, and L-glutamine. These metabolites were involved 28 metabolic pathways and the top 5 metabolic pathways were aspartate metabolism, pyrimidine metabolism, phenylacetate metabolism, methionine metabolism, and fatty acid metabolism. These results suggest that the effect of LBP on DCs function is related to the regulation of cell metabolism.
Currently, atherosclerosis control is important to prevent future heart attacks or strokes. Protein-enriched extract (PE) from housefly maggots (Musca domestica) can inhibit the development of atherosclerosis partially through its antioxidant effects. Whether PE exerts other anti-atherosclerosis functions remains unclear. Here, PE was found to simultaneously promote cholesterol metabolism effects in apolipoprotein E knockout (ApoE −/− ) mice. Bile acid synthesis plays a key role in regulating cholesterol homeostasis in atherosclerosis. Whether PE alleviates atherosclerosis by promoting bile acid production and consequent cholesterol consumption was further explored. First, 8-week-old male ApoE −/− mice were recruited and fed on a cholesterolenriched diet. After 8 weeks, these mice were divided into three groups and received gavage administration of PE, simvastatin, and saline for another 8 weeks. Atherosclerosis severity was then assessed. Real-time quantitative polymerase chain reaction and western blot
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