Hypolipidemic activity and mechanisms of carboxymethyl pachymaran: Impact of the degree of substitution

In this study, carboxymethyl pachymaran (CMP) with three different degrees of substitution were prepared and their hypolipidemic activities were investigated. CMP2 with a substitution degree of 0.791 had different molecular weight and surface smoothness textural profile than CMP1 (0.756) and CMP2 (0.871). All CMPs could reduce 0.5 mM oleic acid-induced lipid accumulation in HepG2 cells, however, CMP2 exhibited a stronger activity than that of CMP1 and CMP3 in lowering lipid and oxidative stress levels. The results demonstrated that CMP2 can reduce lipid levels, serum inflammatory factors and improve liver enzymes in mice. Moreover, the gut microbiota composition was balance and the levels of healthy beneficial short-chain fatty acids were increased treated by CMP2. RT-qPCR analysis demonstrated that CMP2 regulated hepatic and biliary cholesterol efflux by up-regulating the expression levels of LDLR, PPARα, and ABCA1, while down-regulating the expression levels of SREBP-2. CMP2 effectively inhibited lipid accumulation in hepatocytes and attenuates inflammatory injury by a dual regulatory mechanism. Our results revealed potential to develop hypolipidemic functional foods with CMP2.