Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway.

Maslinic acid is a pentacyclic triterpenoid that is distributed in the peel of olives. Previous studies found that maslinic acid inhibited inflammatory response and antioxidant effects. We investigated whether maslinic acid ameliorates nonalcoholic fatty liver disease in mice with high-fat-diet (HFD)-induced obesity and evaluated the regulation of lipogenesis in hepatocytes. Male C57BL/6 mice fed a normal diet or HFD (60% fat, w/w) were tested for 16 wk. After the fourth week, mice were injected intraperitoneally with maslinic acid for 12 wk. In another experiment, HepG2 cells were treated with oleic acid to induce lipid accumulation or maslinic acid to evaluate lipogenesis. Maslinic acid significantly reduced body weight compared with HFD-fed mice. Maslinic acid reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis. Furthermore, serum glucose, leptin, and free fatty acid concentrations significantly reduced, but the serum adiponectin concentration was higher, in the maslinic acid group than in the HFD group. In liver tissue, maslinic acid suppressed transcription factors involved in lipogenesis and increased adipose triglyceride lipase. In vitro, maslinic acid decreased lipogenesis by activating AMPK. These findings suggest that maslinic acid acts against hepatic steatosis by regulating enzyme activity involved in lipogenesis, lipolysis, and fatty acid oxidation in the liver.-Liou, C.-J., Dai, Y.-W., Wang, C.-L., Fang, L.-W., Huang, W.-C. Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway.

Au@SiO2@CuInS2-ZnS/Anti-AFP fluorescent probe improves HCC cell labeling.

BACKGROUND: Clear tumor imaging is essential to the resection of hepatocellular carcinoma (HCC). This study aimed to create a novel biological probe to improve the HCC imaging. METHODS: Au nano-flower particles and CuInS2-ZnS core-shell quantum dots were synthesized by hydrothermal method. Au was coated with porous SiO2 and combined with anti-AFP antibody. HCC cell line HepG2 was used to evaluate the targeting efficacy of the probe, while flow cytometry and MTT assay were used to detect the cytotoxicity and bio-compatibility of the probe. Probes were subcutaneously injected to nude mice to explore light intensity and tissue penetration. RESULTS: The fluorescence stability of the probe was maintained 100% for 24 h, and the brightness value was 4 times stronger than that of the corresponding CuInS2-ZnS quantum dot. In the targeting experiment, the labeled HepG2 emitted yellow fluorescence. In the cytotoxicity experiments, MTT and flow cytometry results showed that the bio-compatibility of the probe was fine, the inhibition rate of HepG2 cell with 60% Cu-QDs/Anti-AFP probe and Au-QDs/Anti-AFP probe solution for 48 h were significantly different (86.3%±7.0% vs. 4.9%±1.3%, t = 19.745, P<0.05), and the apoptosis rates were 83.3%±5.1% vs. 4.4%±0.8% (P<0.001). In the animal experiment, the luminescence of the novel probe can penetrate the abdominal tissues of a mouse, stronger than that of CuInS2-ZnS quantum dot. CONCLUSIONS: The Au@SiO2@CuInS2-ZnS/Anti-AFP probe can targetedly recognize and label HepG2 cells with good bio-compatibility and no toxicity, and the strong tissue penetrability of luminescence may be helpful to surgeons.

Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes.

Previous studies found that phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes.