Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in clinical practice. This study examined the effects of mulberry leaf aqueous extract (MLQE) on lipid metabolism and gut microbiota in mice with high-fat diet-induced NAFLD. Using network pharmacology, we identified key targets of mulberry leaf and stem’s constituents for NAFLD regulation and validated their ameliorative effects through animal experiments. Our results demonstrated that interventions with orlistat (HFO), swimming exercise (HFS), and MLQE (HFM) significantly reduced weight gain, lipid accumulation, and oxidative stress in mace compared to the high-fat control (HFC) group. Histopathological analysis revealed improvements in liver steatosis, hepatocyte arrangement, inflammation, and adipocyte deformation. Molecular analyses indicated decreased mRNA levels of lipid synthesis genes (sterol regulatory element-binding protein 1 (SREBP1), bile salt export pump (BSEP), small heterodimer partner (SHP), and stearoyl-CoA desaturase-1 (SCD1)) and increased protein levels of farnesoid X receptor (FXR) and SHP in the intervention groups, consistent with RNA-seq findings. Additionally, RNA-seq analysis showed upregulation of fibroblast growth factor 21 (FGF21) and suppressor of cytokine signaling 2 (SOCS2), aligning with protein level observations. The interventions also modulated gut microbiota composition, reducing the Firmicutes-to-Bacteroidetes (F/B) ratio and adjusting the abundance of Acetatifactor, Roseburia, and Parasutterella. These findings suggest MLQE as a promising therapeutic approach for NAFLD, with lipid-lowering, antioxidative, and gut microbiota-regulating effects. FGF21 and SOCS2 may be key targets in NAFLD treatment.

Son J, et al. Nutr Res Pract. 2019 Feb;13(1):47-57. https://doi.org/10.4162/nrp.2019.13.1.47

The purpose of this study is to investigate the effect of Agrimonia pilosa Ledeb. extract (APLE) on lipopolysaccharide‐ (LPS‐) induced cell damage in hepatocytes with a focus on antioxidant and anti‐inflammatory activities. Total antioxidant and anti‐inflammatory activities of APLE itself were analyzed and phytochemical analysis was performed. Moreover, inhibitory effects of APLE on LPS‐induced oxidative stress and inflammation were assessed in human HepG2 hepatocytes. APLE was found to exert α,α‐diphenyl‐β‐picrylhydrazyl (DPPH), 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS), and nitrite scavenging activities and reducing power in a dose‐dependent manner. The total phenolic and flavonoid contents of APLE were 44.30 ± 1.61 mg GAE/g and 29.65 ± 1.81 mg QE/g, respectively. HPLC analysis revealed that gallic acid is the major phenolic compound in APLE, followed by rutin, genistein, taxifolin, quercetin, luteolin, and apigenin, in descending order. Treatment of 100 and 200 μg/mL APLE significantly reduced LPS‐stimulated intracellular reactive oxygen species production to the basal level without any cytotoxicity. Oppositely, APLE reversed LPS‐suppressed expression of glutathione peroxidase gene and protein. Consistent with this result, APLE suppressed LPS‐triggered expression of proinflammatory cytokine genes in a dose‐dependent manner. These results reinforce the fact that the antioxidant and anti‐inflammatory activity of APLE helps protect hepatocytes from LPS. Thus, APLE may be utilized as a bioactive ingredient in functional foods.

Pyroptosis plays a critical role in the pathogenesis of mental disorders. However, its specific role and mechanism in arsenic (As)-induced generalized anxiety disorder (GAD) remain elusive. We utilized the data from CtdBbase, Phenopedia and DisGeNet to analyze genes that interact with arsenic poisoning and GAD. Subsequently KEGG and GO enrichment analysis were conducted to preliminatively predict the mechanism of inorganic arsenic-induced GAD. Male Wistar rats were administered water containing NaAsO₂ (50, 100 μg/L) to evaluate GAD-like behavior through open field test and elevated plus maze. The expression of differential miRNAs including miR-425-3p, and pyroptosis in the prefrontal cortex of rats were detected. Furthermore, SKNSH cells were stimulated with NaAsO₂ to examine the molecular changes, and then miR-425-3p mimic was transfected into SKNSH cells to detect pyroptosis in order to verify the function of miR-425-3p. Inorganic arsenic was confirmed to induce GAD-like behavior in rats, characterized by decreased locomotor activity and exploratory activities. Rats with inorganic arsenic-induced GAD exhibited reduced miR-425-3p expression levels in the prefrontal cortex and increased expression of pyroptosis-related proteins, including NF-κB, NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18. Treating with different concentrations of NaAsO₂ showed that inorganic arsenic exposure downregulates miR-425-3p expression in SKNSH cells and upregulates the expression levels of pyroptosis-related proteins. Dual-luciferase reporter gene experiments demonstrated that miR-425-3p targets the NFKB1. Overexpressing miR-425-3p reversed the inorganic arsenic-induced pyroptosis in SKNSH cells by inhibiting the expression of NF-κB, NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18. Our findings suggest that inorganic arsenic exposure may induce GAD-like behavior in rats by downregulating miR-425-3p in prefrontal cortex, which targets NF-κB and regulates pyroptosis in neuronal cells.

This study was aimed to investigate the effect of Guisangyou tea (GSY tea) in improving abnormal lipid metabolism in mice with obesity induced by a high-fat diet (HFD). The results showed that intervention of the water extract of GSY tea (WE) decreased serum levels of lipids, and positively regulated the related antioxidant enzyme activities and the inflammatory factors in the serum and liver. In the liver, the mRNA and protein expression levels of sterol regulatory element-binding proteins-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD-1), fatty acid synthase (FASN), and acetyl CoA carboxylase (ACC) related to lipid synthesis were downregulated, and the mRNA and protein expression levels of the farnesoid X receptor (FXR) and small heterodimer partner (SHP) related to bile acid production were upregulated. The results demonstrate that GSY tea can improve abnormal lipid metabolism in obese mice by improving the body’s antioxidant capacity, regulating the inflammatory state, and reducing the synthesis of lipids and increasing the production of bile acids. GSY tea can be processed and utilized as a safe and effective resource for improving abnormal lipid metabolism.