Dimethyloxalylglycine Suppresses SREBP1c and Lipogenic Gene Expressions in Hepatocytes Independently of HIF1A.

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.

Novel treatment of acute and acute-on-chronic liver failure: Interleukin-22.

Acute liver failure (ALF) is a life-threatening medical condition, characterized by rapidly progressive hepatic dysfunction, coagulopathy and hepatic encephalopathy in patients without chronic liver disease, while acute-on-chronic liver failure (ACLF) occurs in patients with existing chronic liver disease. ALF and ACLF are often associated with multiple organ failure and a high short-term mortality. In this review, we briefly discuss the causes and pathogenesis of ALF and ACLF, the current options available for the treatment of both deadly maladies and interleukin-22 (IL-22), a novel promising drug that may have great therapeutic potential for ALF and ACLF treatment. IL-22 is a cytokine produced by immune cells but mainly targets epithelial cells including hepatocytes. IL-22 has been shown to protect against organ damage and reduce bacterial infection in many preclinical models and several clinical trials including alcohol-associated hepatitis. The potential application of IL-22 for the treatment of ALF and ACLF is also elaborated.

Protective effect of fermented aloe extract on glutamate-induced cytotoxicity in HT22 cells.

Excessive 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.