hyperoside and Liver-Cirrhosis

Oxidative stress and inflammation have been implicated in hepatic fibrosis. Antioxidant and anti-inflammatory activities are among the pharmacological effects of hyperoside. This study aimed to evaluate the impact of hyperoside on hepatic fibrosis and elucidate the underlying processes that perpetuate this relationship. The findings indicated that hyperoside significantly protects mouse livers against damage, inflammation, and fibrosis. Specifically, attenuation of hepatic fibrosis is associated with lower expression of HMGB1 protein and reduced expression of Toll-like receptor 4, PARP-1, and nuclear factor-kB (NF-κB) p65 mRNA and protein. Furthermore, hyperoside inhibited the cytoplasmic translocation of HMGB1 and nuclear localization of NF-κB p65 in the hepatic tissues of mice. The results of this study indicate that hyperoside may impose a blocking or reversing effect on hepatic fibrosis; additionally, the corresponding hyperoside-dependent mechanism may be linked to PARP-1-HMGB1 pathway regulation.

Topics: Adenosine Diphosphate Ribose; Animals; Carbon Tetrachloride; HMGB1 Protein; Inflammation; Liver Cirrhosis; Mice; NF-kappa B; Poly(ADP-ribose) Polymerase Inhibitors

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. To date, no medications for NAFLD have been approved by relevant governmental agencies. Emerging evidence indicates that innate immune mechanisms are pivotal drivers of inflammation and other pathological manifestations observed in NAFLD. Hyperoside, a flavonoid compound mainly found in medicinal plants, has many biological effects, but the role of hyperoside in the physiological process of NAFLD is poorly defined. This study demonstrated that hyperoside exerts protective effects against high-fat diet (HFD)-induced NAFLD and regulates macrophage polarization in an Nr4A1-dependent manner. After 16 weeks on a HFD, hepatic steatosis, insulin resistance, and inflammatory responses were significantly ameliorated in hyperoside-treated HFD-fed wild-type mice, and hyperoside facilitated the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 subtype. Nr4A1 was found to be upregulated in hyperoside-treated HFD-fed mice, and hyperoside did not improve HFD-induced NAFLD or regulate macrophage polarization in Nr4A1-deficient mice. In conclusion, hyperoside may have therapeutic potential in preventing the pathological progression of NAFLD.

Topics: Animals; Diet, High-Fat; Liver; Liver Cirrhosis; Macrophages; Male; Mice, Inbred C57BL; Mice, Knockout; Non-alcoholic Fatty Liver Disease; Nuclear Receptor Subfamily 4, Group A, Member 1; Quercetin

Heart failure (HF) is an end-stage of various serious cardiovascular diseases, which causes liver injury. Hyperoside has been reported to exert protective effect on liver injury and fibrosis. However, the role and related mechanisms of hyperoside in HF-induced liver fibrosis are still unclear. In the current study, we established a model of HF via aortocaval fistula (ACF) in rats in vivo. Hyperoside treatment in ACF rats increased cardiac output, the maximum peak rate of rise/fall in left ventricular pressure (+dP/dt, -dP/dt) and LV ejection fraction (LVEF), decreased LV end-systolic pressure (LVESP), LV end-diastolic pressure (LVEDP) and LV end-systolic volume (LVESV), and reduced heart weight/body weight ratio in a dose-dependent manner. Moreover, hyperoside could attenuate liver fibrosis and injury in ACF rats, as evidenced by reduction of fibrosis area and hydroxyproline content, amelioration of edema and degeneration of liver cell vacuoles, and inhibition of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels. Further, α-smooth-muscle actin (α-SMA), collagen I, profibrotic factor-connective tissue growth factor (CTGF), matrix metalloproteinase-2 (MMP2) and MMP9 levels were down-regulated in hyperoside-treated ACF rats. Additionally, hyperoside inhibited the activation of TGF-β1/Smad pathway. Finally, we confirmed that hyperoside suppressed TGF-β1-mediated hepatic stellate cell activation in vitro. Collectively, hyperoside showed a suppressive role in HF-induced liver fibrosis and injury.

Topics: Animals; Disease Models, Animal; Heart Failure; Hepatic Stellate Cells; Liver; Liver Cirrhosis; Male; Quercetin; Rats; Rats, Wistar

Hyperoside was used to treat cardiovascular disease for many years in China. It was shown great effect on regulation of lipid metabolism. But there is lack of reports about the effects of hyperoside on liver diseases.. This study was designed to investigate the potentially protective effects of hyperoside and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation on Carbon Tetrachloride (CCl. All mice were divided into six groups containing 6 animals per group. Mice in different group were given relative processing for 4 weeks. The potentially protective effects of hyperoside on CCl. CCl. Hyperoside increased the activity of the antioxidant and phase II detoxifying enzymes through the activation of Nrf2 nuclear translocated in the CCl

Topics: Animals; Antioxidants; Carbon Tetrachloride; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; Mice; NF-E2-Related Factor 2; Quercetin; Up-Regulation

Hyperoside, an active compound found in plants of the genera Hypericum and Crataegus, is reported to exhibit antioxidant, anticancer, and anti-inflammatory activities. Induction of hepatic stellate cell (HSC) apoptosis is recognized as a promising strategy for attenuation of hepatic fibrosis. In this study, we investigated whether hyperoside treatment can exert antifibrotic effects in human LX-2 hepatic stellate cells. We found that hyperoside induced apoptosis in LX-2 cells and decreased levels of α-smooth muscle actin (α-SMA), type I collagen, and intracellular reactive oxygen species (ROS). Remarkably, hyperoside also inhibited the DNA-binding activity of the transcription factor NF-κB and altered expression levels of NF-κB-regulated genes related to apoptosis, including proapoptotic genes Bcl-Xs, DR4, Fas, and FasL and anti-apoptotic genes A20, c-IAP1, Bcl-X L , and RIP1. Our results suggest that hyperoside may have potential as a therapeutic agent for the treatment of liver fibrosis.

Topics: Apoptosis; Cell Line; Dietary Supplements; Flavonoids; Genetic Diseases, Inborn; Hepatic Stellate Cells; Humans; Liver Cirrhosis; NF-kappa B; Quercetin; Reactive Oxygen Species; Signal Transduction