Ginger polysaccharide promotes myeloid-derived suppressor cell apoptosis by regulating lipid metabolism.

Recently, targeting myeloid-derived suppressor cells (MDSCs) which mainly play an immunosuppressive role in tumor microenvironment has become a hot spot in tumor immunotherapy. This study focuses on biological effect of ginger polysaccharide extracted from natural plants on promoting apoptosis of MDSCs by regulating lipid metabolism. An MTT assay was used to detect the inhibitory effect of ginger polysaccharide on the growth of an MDSC-like cell line (MSC-2). The apoptosis-promoting effect of ginger polysaccharide on MSC-2 cells was detected by flow cytometry. Expression levels of apoptosis proteins (caspase 9 and Bcl-2) and lipid metabolism enzymes (fatty acid synthase (FASN) and diacylglycerol acyltransferase 2) in MSC-2 cells treated with different concentrations of ginger polysaccharide were detected by western blot assay. Nile red staining was used to quantitatively detect the effect of ginger polysaccharide on lipid droplet synthesis. Ginger polysaccharide inhibited proliferation of MSC-2 cells and promoted their apoptosis by upregulating pro-apoptotic caspase 9 protein, downregulating anti-apoptotic Bcl-2 protein, inhibiting expression of FASN and diacylglycerol acyltransferase 2 (key enzymes in fatty acid synthesis and lipid droplet formation, respectively). Ginger polysaccharide promoted apoptosis of MDSCs by regulating key lipid metabolism enzymes, inhibiting fatty acid synthesis and lipid droplet accumulation, and reducing the energy supply of cells.

[Effect of Danlou Tablets on alleviating hepatic adipogenesis, inflammatory response, and insulin resistance in db/db mice].

This study explored the effect and potential mechanism of Danlou Tablets(DLT) on insulin resistance in db/db mice with type 2 diabetic mellitus(T2 DM). The db/db male mice were randomly assigned into model control(MC) group, metformin(MET, tablet, 100 mg·kg~(-1)) group, and DLT(1 g·kg~(-1)) group, and C57 BL/6 J mice were taken as normal control(NC) group. The mice in the MET group and DLT group were given corresponding drugs by gavage once a day for 16 weeks. The fasting blood glucose, glucose tolerance, and insulin tolerance were measured to evaluate the effect of DLT on blood glucose and insulin resistance in diabetic mice. The serum free fatty acid, triacylglycerol, and total cholesterol levels were determined to evaluate the effect of DLT on blood lipids in diabetic mice. The liver index and perirenal fat index were calculated to measure the effect of DLT on lipid accumulation in non-adipose tissue and adipose tissue. Western blot was performed to determine the protein levels of insulin receptor-ß(IRß), phospho-IRß(p-IRß), phosphatidylinositol 3-kinase(PI3 K), and insulin receptor substrate-1(IRS-1) involved in IRS-1/PI3 K/Akt signaling pathway in the livers of mice to reveal the mechanism of DLT in alleviating insulin resistance in diabetic mice. The protein levels of sterol regulatory element binding protein-1(SREBP-1) and the mRNA levels of sterol regulatory element binding protein-1 c(SREBP-1 c), fatty acid synthase(FAS), acetyl-CoA carboxylase(ACC), diacylglycerol acyltransferase-1(Dgat1), and diacylglycerol acyltransferase-2(Dgat2) involved in the SREBP-1/FAS signaling pathway were detected to evaluate the effect of DLT on lipid metabolism in diabetic mice. Real-time quantitative PCR was employed to determine the mRNA levels of galectin-3(Gal-3), interleukin-6(IL-6), and monocyte chemoattractant protein-1(MCP-1) in mouse liver to evaluate the effect of DLT on inflammatory response in diabetic mice. The results showed that DLT significantly reduced the blood glucose and lipid levels and alleviated the insulin resistance in diabetic mice. Compared with the MC group, DLT significantly up-regulated the protein levels of p-IRß, PI3 K, and IRS-1(P<0.05 or P<0.01), and down-regulated the protein level of SREBP-1 in liver tissues of diabetic mice(P<0.05). DLT lowered the mRNA levels of SREBP-1 c, FAS, ACC, Dgat1, and Dgat2 related to lipid metabolism as well as those of Gal-3, IL-6, and MCP-1 associated with inflammation in the livers of diabetic mice(P<0.05 or P<0.01). The findings of this study suggest that DLT may alleviate insulin resistance in diabetic mice by regulating IRS-1/PI3 K/Akt signaling pathway and SREBP-1/FAS signaling pathway to reduce lipid production and inhibit inflammatory response.