6-Shogaol alleviates high-fat diet induced hepatic steatosis through miR-3066-5p/Grem2 pathway.

The purpose of this study is to investigate the mechanism by which 6-shogaol ameliorates hepatic steatosis via miRNA-mRNA interaction analysis. C57BL/6 J mice were fed a high-fat diet (HFD) for 12 weeks, during which 6-shogaol was administered orally. The liver lipid level, liver function and oxidative damage in mice were evaluated. mRNA sequencing, miRNA sequencing, and RT-qPCR were employed to compare the expression profiles between the HFD group and the 6-shogaol-treated group. High-throughput sequencing was used to construct the mRNA and miRNA libraries. Target prediction and integration analysis identified eight potential miRNA-mRNA pairs involved in hepatic steatosis, which were subsequently validated in liver tissues and AML12 cells. The findings revealed that 6-shogaol modulates the miR-3066-5p/Grem2 pathway, thereby improving hepatic steatosis. This study provides new insights into the mechanisms through which 6-shogaol alleviates hepatic steatosis, establishing a foundation for future research on natural active compounds for the treatment of metabolic diseases.

Effects of 6-Shogaol on Glucose Uptake and Intestinal Barrier Integrity in Caco-2 Cells.

As the main bioactive component in dried ginger, 6-shogaol has potential hypoglycemic activity, but its mechanism is still unclear. The process of carbohydrate digestion and glucose absorption is closely related to the enzymatic activity of epithelial brush cells, expression of glucose transporters, and permeability of intestinal epithelial cells. Therefore, this study explored the hypoglycemic mechanism of 6-shogaol from the perspective of glucose uptake, absorption transport, and protection of intestinal barrier function. Based on molecular docking, the binding energy of 6-shogaol and α-glucosidase is -6.24 kcal/mol, showing a high binding affinity. Moreover, a-glucosidase enzymatic activity was reduced (-78.96%) when the 6-shogaol concentration was 500 µg/mL. After 6-shogaol intervention, the glucose uptake was reduced; the relative expression of glucose transporters GLUT2 and SGLT1 were down regulated; and tight junction proteins ZO-1, Occludin and Claudin were up regulated in differentiated Caco-2 cells. This study confirmed that 6-shogaol effectively inhibits the activity of α-glucosidase and has beneficial effects on glucose uptake, protection of intestinal barrier function, and promotion of intestinal material absorption.

Metabonomics and the gut microbiome analysis of the effect of 6-shogaol on improving obesity.

This study investigated the ability of 6-shogaol to reduce obesity in C57BL/6J mice fed with high-fat diet (HFD). After 12 weeks of 6-shogaol (20, 40, 60 mg/kg/2 days) intervention, obesity related indicators, gut microbiota and metabonomics of mice were analyzed. The obesity degree and blood lipid level of mice treated with 6-shogaol were reduced, and glucose homeostasis was improved, especially in mice treated with low-dose. The intervention of 6-shogaol increased the diversity of gut microbiota and decreased the ratio of Firmicutes and Bacteroides. 6-shogaol also led to changes in metabonomics. There were 5, 4 and 6 different metabolites of 6-shogaol at low, medium and high doses. Among them, Solacauline, PE (22:5 (4Z, 7z, 10z, 13z, 13z, 16z)/14:1 (9z)) and presqualene diphosphate have strong correlation with Akkermansia, Brucella, Odoribacter and Mucispirillum. This study aims to provide a theoretical foundation for clarifying the molecular mechanism of 6-shogaol in improving obesity.

Integrated network pharmacology and cellular assay for the investigation of an anti-obesity effect of 6-shogaol.

This study explored the anti-obesity effect of 6-shogaol and the underlying mechanisms by using Network pharmacology for the prediction and verification of molecular targets and pathways of 6-shogaol against obesity. Furthermore, the results were verified by molecular docking and cell experiments. A total of 86 core targets of 6-shogaol towards obesity were identified. Among them, AKT1 and PIK3CA were confirmed by using the molecular docking. In 3T3-L1 preadipocyte model, 6-shogaol significantly inhibited proliferation and differentiation, reducing the accumulation of lipid droplets. Compared with the control group, the inhibition rates of 6-shogaol on TG and TC were 90.8% and 40.0%, respectively. Additionally, 6-shogaol down-regulated the expression of PPAR-γ and C/EBP-α, while it decreased the phosphorylation of IRS-1, PI3K and AKT. This study, for the first time, confirmed the effect of 6-shogaol on improving obesity through PI3K/AKT pathway. An anti-obesity bioactivity study was further recommended for the development of novel anti-obesity products.