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Dimethyloxalylglycine (DMOG) is a representative inhibitor of the prolyl hydroxylase domain (PHD), which mediates the degradation of hypoxia-inducible factor-1-alpha (HIF1A). DMOG exerts its pharmacological effects via the canonical pathway that involves PHD inhibition; however, it remains unclear whether DMOG affects lipogenic gene expression in hepatocytes. We aimed to elucidate the effects of DMOG on sterol regulatory element-binding protein-1c (SREBP1c), a master regulator of fatty acid synthesis in hepatocytes. DMOG treatment inhibited SREBP1c mRNA and protein expression in HepG2 and AML12 hepatocytes and reduced the transcript levels of SREBP1c-regulated lipogenic genes. A luciferase reporter assay revealed that DMOG inhibited the transcriptional activity of SREBP1c. Moreover, DMOG suppressed SREBP1c expression in mice liver. Mechanistically, treatment with DMOG enhanced the expression of HIF1A and insulin-induced gene 2 (INSIG2), which inhibits the activation of SREBP1c. However, HIF1A or INSIG2 knockdown failed to reverse the inhibitory effect of DMOG on SREBP1c expression, suggesting a redundant role of HIF1A and INSIG2 in terms of repressing SREBP1c. DMOG did not function through the canonical pathway involving inhibition of SREBP1c by PHD, highlighting the presence of non-canonical pathways that mediate its anti-lipogenic effect.

Non-alcoholic fatty liver disease (NAFLD) is characterized by a spectrum of hepatic diseases, including fatty liver, non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. NAFLD is a hepatic manifestation of metabolic syndrome and has become the leading cause of liver transplantation, necessitating an in-depth understanding of its underlying pathogenic mechanisms and the identification of viable drug targets. Although fatty liver is benign and does not exert marked liver damage or inflammation, NAFLD progression involves inflammatory processes facilitated by immune cells. Macrophages and monocytes constitute the pool of innate immune cells that contribute to NAFLD development in association with other cell types, such as neutrophils, T cells, and natural killer cells. The concept that macrophages contribute to the inflammatory processes in NAFLD development has long been debated; however, the remarkable advances in experimental techniques have rapidly uncovered new subpopulations of macrophages and monocytes, whose functions need to be comprehensively elucidated. The current review focuses on the recent expansion of our knowledge of the heterogeneous population of macrophages crucially involved in NAFLD development. In addition, the present paper discusses ongoing efforts to target macrophages and inflammatory processes to develop optimal therapeutic agents against non-alcoholic steatohepatitis.

ABSTRACTExcessive glutamate can cause oxidative stress in neuronal cells and this can significantly contribute to the etiology of neurodegenerative disease. The present study mainly aims to investigate that aloe extract (AE) and fermented aloe extract (FAE) could protect against glutamate-induced cytotoxicity by modulating oxidative stress. In this study, both AE and FAE showed potent neuroprotective activity by inhibiting ROS and Ca2+ concentration, increasing mitochondria membrane potential, and activating glutathione-related enzymes against glutamate-insulted neurotoxicity in HT22 cells. In addition, the neuroprotective activity of FAE was more potent than that of AE. HPLC analysis reveals that the chemical composition of FAE is different from that of AE. Especially, the contents of aloin A, aloin B and aloenin were higher in FAE than in AE. In conclusion, this study indicates that both AE and FAE may have effective neuroprotective activity in glutamate-insulted pathological conditions such as Alzheimer’s disease by managing oxidative stress.

Aloe is widely used as a cosmetic and medicinal plant. Numerous studies have reported that aloe gel extract has antioxidant, anticancer, antidiabetic, immunity, and skin antiaging properties. However, few studies have investigated the properties of fermentation products of aloe processing byproducts. Aloe stalks and leaves remain as byproducts after the aloe beverage manufacturing process. This study evaluated whether fermentation products of blender and press extracts of aloe processing byproducts (BF and PF, respectively) that remain after beverage manufacturing were useful as functional biomaterial by investigating their effects on adipocyte differentiation, hyaluronic acid (HA) production, tyrosinase activity, and antioxidant activity. Co-fermentation of G. xylinus and S. cerevisiae was conducted for fermentation of aloe processing byproducts. The BF and PF products did not induce observable cytotoxicity effects. However, BF and PF products did inhibit a 3T3-L1 adipocyte differentiation compared with control, with the BF product displaying greater inhibition of 3T3-L1 adipocyte differentiation than the PF product. HA production increased in HaCaT cell cultures as the concentration of the MF product increased, as compared with the untreated control. The levels of tyrosinase inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and superoxide dismutase (SOD)-like activity also depended on the MF product concentration. This study indicates that the fermented products of aloe processing byproducts have biological potential for applications in the manufacturing of cosmetics, pharmaceuticals, and beverages. These laboratory bench results provide the foundation for future studies of scaling and practical applications at the industrial level. [ABSTRACT FROM AUTHOR]