Dihydroartemisinin ameliorates the liver steatosis in metabolic associated fatty liver disease mice by attenuating the inflammation and oxidative stress and promoting autophagy.

PURPOSE: To explore the effect and potential mechanism of dihydroartemisinin (DHA) on metabolism-related fatty liver disease. METHODS: A metabolic associated fatty liver disease (MAFLD) mice model was induced with continuous supplies of high-fat diet. DHA was intraperitoneally injected into mice. The weight of mice was monitored. The concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in serum were detected by an automatic biochemical analyzer. The liver tissues were stained by hematoxylin and eosin and oil red O. The level of inflammation, oxidative stress, and autophagy was assessed by reverse transcription polymerase chain reaction, biochemical examination, Western blot and transmission electron microscope assays. RESULTS: DHA treatment reduced theMAFLD-enhanced the level of weight gain, the concentrations of TC, TG, LDL and malonaldehyde, while increasedthe MAFLD-decreased the concentrations of HDL and superoxide dismutase. DHA ameliorated the MAFLD-aggravated pathological changes and the number of lipid droplets. Low dose of DHA declined the MAFLD-induced the enhancement of the expression of inflammatory factor. DHA treatment increased the MAFLD-enhanced the level of autophagy related protein, while decreased the MAFLD-reduced the protein level of p62. The increased level of autophagy was confirmed by transmission electron microscope. CONCLUSIONS: DHA can improve liver steatosis in MAFLD mice by inhibiting inflammation and oxidative stress and promoting autophagy.

Dihydroartemisinin ameliorates the liver steatosis in metabolic associated fatty liver disease mice by attenuating the inflammation and oxidative stress and promoting autophagy

ABSTRACT Purpose: To explore the effect and potential mechanism of dihydroartemisinin (DHA) on metabolism-related fatty liver disease. Methods: A metabolic associated fatty liver disease (MAFLD) mice model was induced with continuous supplies of high-fat diet. DHA was intraperitoneally injected into mice. The weight of mice was monitored. The concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in serum were detected by an automatic biochemical analyzer. The liver tissues were stained by hematoxylin and eosin and oil red O. The level of inflammation, oxidative stress, and autophagy was assessed by reverse transcription polymerase chain reaction, biochemical examination, Western blot and transmission electron microscope assays. Results: DHA treatment reduced theMAFLD-enhanced the level of weight gain, the concentrations of TC, TG, LDL and malonaldehyde, while increasedthe MAFLD-decreased the concentrations of HDL and superoxide dismutase. DHA ameliorated the MAFLD-aggravated pathological changes and the number of lipid droplets. Low dose of DHA declined the MAFLD-induced the enhancement of the expression of inflammatory factor. DHA treatment increased the MAFLD-enhanced the level of autophagy related protein, while decreased the MAFLD-reduced the protein level of p62. The increased level of autophagy was confirmed by transmission electron microscope. Conclusions: DHA can improve liver steatosis in MAFLD mice by inhibiting inflammation and oxidative stress and promoting autophagy.

MicroRNA-122-5p Inhibition Improves Inflammation and Oxidative Stress Damage in Dietary-Induced Non-alcoholic Fatty Liver Disease Through Targeting FOXO3.

Misregulated microRNA network has been emerging as the main regulator in non-alcoholic fatty liver disease (NAFLD). The deregulation of miR-122-5p is associated with the liver disease. However, the specific role and molecular mechanism of miR-122-5p in NAFLD remain unclear. In this study, we have reported that the high-fat diet (HFD) or palmitic acid (PA) significantly upregulated the hepatic miR-122-5p expression in vivo and in vitro. Inhibition of miR-122-5p suppressed accumulation-induced inflammation of lipids and oxidative stress damage in PA-treated L02 cells and HFD-induced fatty liver. The effect of the miR-122-5p inhibitor on NAFLD did not depend on insulin resistance-mediated PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway but rather on the upregulation of its downstream FOXO3. Subsequently, we validated that miR-122-5p directly binds to the predicted 3'-UTR of FOXO3 to inhibit its gene expression. Conversely, silencing FOXO3 abolished the hepatic benefits of miR-122-5p inhibition to obese mice by decreasing the activity of antioxidant enzymes of superoxide dismutase (SOD). This study provides a novel finding that FOXO3 was the target gene of miR-122-5p to attenuate inflammatory response and oxidative stress damage in dietary-induced NAFLD. Our study provided evidence to reveal the physiological role of miR-122-5p in dietary-induced NAFLD.

The miR-122 inhibition alleviates lipid accumulation and inflammation in NAFLD cell model.

BACKGROUND: Accumulating evidence showed that the expression of miR-122 was abnormal in NAFLD patients; however, the role of miR-122 on lipid accumulation and inflammation in NAFLD is not clear. METHODS: RT-qPCR was applied to detect the expression levels of miR-122 and pro-inflammatory cytokines following transfected with miR-122 inhibitor or treated with oleic acid (OA). Detection of lipid accumulation was performed by triglyceride content test and oil red o staining assay. Western blotting was applied to detect the protein levels of TLR7, TLR4, MyD88 and NF-κBp65. RESULTS: We found that the OA promoted lipid accumulation and pro-inflammatory cytokines secretion and activated TLR4/MyD88/NF-κBp65 signalling pathway, which were restored following transfected with miR-122 inhibitor. CONCLUSIONS: These results suggested that miR-122 inhibition alleviates lipid accumulation and inflammation in L02 cell induced by OA may through inhibiting TLR4/MyD88/NF-κBp65 signalling pathway. The protective mechanism of miR-122 inhibition in NAFLD must be explored in future studies.