Cordycepin attenuates high-fat diet-induced non-alcoholic fatty liver disease via down-regulation of lipid metabolism and inflammatory responses.

Cordycepin (CRD), an adenosine analog derived from traditional Chinese medicine, is an active component in Cordyceps militaris. It has been shown to have many protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). This study aims to explore the effects of CRD on obesity-induced NAFLD. In this experiment, C57BL/6 J mice were randomly assigned into normal control group (NC), high fat diet group (HFD) and HFD + CRD group for 8 weeks. The body weights were recorded weekly, at the end of the experiments, the liver and serum samples were collected. We found that CRD administration reduced body weight and decreased the weight of adipose and liver, and CRD relieved liver injure through diminishing of histopathological changes and decreasing serum levels of AST, ALT, TG, TC, LDL-C and increased the level of HDL-C. Furthermore, treatment with CRD significantly alleviated expression of inflammatory factors (TNF-α, IL-6 and Il-1ß) and macrophage markers (MCP1, MIP2, mKC and VCAM1). On the other hand, compared with HFD group, the CRD treated group markedly down-regulated relative proteins of lipid anabolism (SREBP1-c, ACC, SCD-1, LXRα and CD36) and up-regulated relative proteins of ß-oxidation (p-AMPK, AMPK, CPT-1 and PPARα). In summary, our results suggest that CRD can be a potential therapeutic agent in the prevention and treatment of NAFLD, which may be closely related to its effect on lipid metabolism and inflammatory responses.

Hepatoprotective effect of quercetin against LPS/d-GalN induced acute liver injury in mice by inhibiting the IKK/NF-κB and MAPK signal pathways.

Quercetin is regarded as a potential hepatoprotective agent in the treatment of acute liver injury. However, the underlying mechanism of how quercetin to protect against lipopolysaccharides/d-galactosamine (LPS/d-GalN) induced acute liver injury remains unclear. To investigate the mechanism, the antioxidative, anti-inflammatory and antiapoptotic responses were performed. The results showed that quercetin pretreatment improved the survival rate and substantially reduced the liver histopathological changes in mice. It also alleviated the hepatic damage and reduced the productions of oxidative markers induced by LPS/d-GalN. In addition, quercetin pretreatment significantly diminished the production of inflammatory cytokines, including TNF-α, IL-6 and IL-1ß, and inhibited the activation of the NF-κB and MAPK signaling pathways as well as the expression of apoptotic-related proteins induced by LPS/d-GalN. We found that the potential mechanism of this quercetin-induced protection is mainly mediated through its powerful antioxidative capacity, inhibition of hepatocyte apoptosis and suppression of inflammatory cytokines through the IKK/NF-κB and MAPK signaling pathways. Thus, quercetin shows a promising therapeutic effect on acute liver injury in mice.

Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice.

To investigate the effects and mechanism of diosmetin on acute hepatic failure (AHF), an AHF murine model was established through administration of lipopolysaccharides/D-galactosamine (LPS/D-GalN). In vitro, diosmetin scavenged free radicals. In vivo, diosmetin decreased mortality among mice, blocked the development of histopathological changes and hepatic damage, and suppressed levels of inflammatory mediators and cytokines. In addition, diosmetin prevented the expression of phosphorylated IKK, IκBα, and NF-κB p65 in the NF-κB signaling pathway, and JNK and p38 in the MAPK signaling pathway. Diosmetin also inhibited hepatocyte apoptosis. Thus, diosmetin exerts protective effects against endotoxin-induced acute hepatic failure in mice. The underlying mechanisms are antioxidation, NF-κB signaling inhibition, inflammatory mediator/cytokine attenuation, and hepatocyte apoptosis suppression. Diosmetin is thus a potential drug candidate for use in the treatment of acute hepatic failure.

Antioxidation, anti-inflammation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice.

To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/d-GalN. Catalase, glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/d-GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E2 (PGE2). In addition, Pae administration prevented the phosphorylated expression of IκB kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/d-GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-κB and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/d-GalN-induced ALF in the future.

Lattice Boltzmann simulation of a single charged particle in a Newtonian fluid.

The lattice Boltzmann method is used to study the sedimentaion of a single charged circular cylinder in a two-dimensional channel in a Newtonian fluid. When the dielectric constant of the liquid is smaller than that of the walls, there are attractive forces between the particle and the walls. The hydrodynamic force pushes the particle towards the centerline at low Reynolds numbers. Due to the competition between the Coulomb force and the hydrodynamic force in opposite directions, there is a critical linear charge density q(c) at which the particle will fall vertically off centerline, which is a metastable state in addition to the stable state on centerline, for any initial position of the particle sufficiently far from the proximal wall. It is found that the rotation of the particle plays an important role in the stability of such metastable states. The particle hits on the wall or falls on the centerline when the linear charge density on the particle is greater or less than q(c). The simulation method and the new phenomena are also helpful in the study of charged multiparticle suspensions.