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. Graphical
The platinum-based drugs prevail in the therapy of malignant tumors treatment. However, their clinical outcomes have been heavily restricted by severe systemic toxicities. To ensure biosafety and efficiency, herein, we constructed a disulfide bond inserted Pt(IV) self-assembled nanoplatform that is selectively activated by rich glutathione (GSH) in tumor site. Disulfide bond was introduced into the conjugates of oxaliplatin (IV) and oleic acid (OA) which conferred cascade reduction-responsiveness to nanoassemblies. Disulfide bond cleavage and reduction of Pt(IV) center occur sequentially as a cascade process. In comparison to oxaliplatin solution, Pt(IV) nanoparticles (NPs) achieved prolonged blood circulation and higher maximum tolerated doses. Furthermore, Oxa(IV)-SS-OA prodrug NPs exhibited potent anti-tumor efficiency against 4T1 cells and low toxicities in other normal tissues, which offers a promising nano-platform for potential clinical application.