Bioactive Polysaccharides From <i>Cremastra Appendiculata</i> Attenuate Lipid Accumulation In Vitro Model of Non‐Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic disease with a rapidly growing incidence worldwide, presenting as an ever-increasing burden to the healthcare system. In this study, we explored that Cremastra appendiculata, a valuable traditional medicine in China, could alleviate lipid accumulation in HepG2 cells. C. appendiculata polysaccharide (CAP) was extracted from the pseudobulbs of C. appendiculata and oligosaccharide (oligoCAP) was obtained by enzymatical digestion of the CAP with endo-β-mannanase. Molecular weight of CAP and oligoCAP was determined to be 46 415 and 933 Da. Oleic acid (OA) induced steatosis in HepG2 cells was adopted as an in vitro NAFLD model. CAP and oligoCAP could reduce the OA-induced lipid accumulation and significantly reduce the total cholesterol and triglyceride content in the HepG2 cells. CAP and oligoCAP possessed lipid-lowering and anti-inflammatory activities especially by enhancing lipolysis and suppressing lipid synthesis shown by quantitative polymerase chain reaction results. Transcriptome analysis showed that CAP and oligoCAP mainly played anti-NAFLD roles in the pathways of lipid metabolism and necroptosis. Moreover, in vivo biodistribution results showed that both CAP and oligoCAP were mostly distributed in the small intestine and stomach tissues 24 h after administration, which may be related to the structural and molecular weight characterization of the polysaccharides.