Regressive Effect of Myricetin on Hepatic Steatosis in Mice Fed a High-Fat Diet

Abstract

Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR) signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.

Myricetin Modulates Macrophage Polarization and Mitigates Liver Inflammation and Fibrosis in a Murine Model of Nonalcoholic Steatohepatitis

“…Indeed, our results confirmed that myricetin-treated to NASH mice effectively inhibited the activation of HSCs and hepatic fibrosis compared with vehicle-treated mice on the same diet (Figure 3). Supported our data, myricetin attenuated liver fibrosis-induced by CCl 4 in mice (29,32) and ameliorated high-fat diet-induced obesity and IR through enhancing antioxidant capacity (34). However, the exact molecular mechanisms by which myricetin exerts its beneficial effects on liver inflammation and fibrosis in NASH has been largely unknown.…”

“…In particular, myricetin has proved to inhibit fatty acid biosynthesis and attenuate ethanol-induced lipid accumulation in liver cells (30). Furthermore, myricetin treatment also ameliorates hyperglycemia, IR, and steatosis in mouse models of obesity through antioxidant properties (33,34). These findings indicate that supplementation of the diet with myricetin might be beneficial to NASH and liver fibrosis.…”

“…Myricetin (3,3 ′ ,4 ′ ,5,5 ′ ,7-hexahydroxyflavone; Figure 1A) is a polyphenol flavonoid that is widely found in most berries such as blueberries and strawberries, tea, vegetables, and various medicinal herbs (27)(28)(29). Myricetin is reported to possess many pharmacological properties, including antioxidant, anti-inflammatory, antifibrotic, anti-obesity, and anti-diabetic activities (27)(28)(29)(30)(31)(32)(33)(34). Recent studies have also demonstrated that myricetin attenuated vascular endothelial dysfunction and hepatic injury in mice induced by high choline-fed (31) and mitigated liver fibrosis induced by CCl 4 in mice (29,32).…”

To Evaluate the Antidiabetic and Rejuvenating Capability of Tissues on Alloxan Induced Diabetic Rats under the Effect of Ethanolic Leaf Extract of Coriandrum sativum: A Histopathological Study

“…The degradation of starch rapidly and leads to elevation of blood glucose level. 34 on the other hand administration of ethanolic extract on alloxan induced diabetic rats, the increased level has significantly decreased. 35 Lipase is an enzyme that plays vital role in lipid metabolism which is employed in human and animal model studies.…”

Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease

“…Therefore, mice lacking NRF2 develop more severe NASH than do wild-type mice fed a HFD [16,17]. On the other hand, HFD-or alcohol-induced downregulation of Nrf2 and its target genes contributes to the development of FLD by lowering the thresholds for the unfolded protein response and inflammation, increasing lipogenesis, and inhibiting the ability to protect against oxidative stress [18,19]. AMPK-NRF2 axis is an important intracellular signaling pathway leading to ARE-dependent transcriptional activation.…”