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High fructose-feeding is an essential causative factor leading to the development and progression of hepatitis associated with high levels of endotoxin (LPS). Juglanin, as a natural compound extracted from the crude Polygonum aviculare, displayed inhibitory activity against inflammation response and cancer growth. However, researches about its role on anti-inflammation and apoptosis are far from available. Here, it is the first time that juglanin was administrated to investigate whether it inhibits fructose-feeding-induced hepatitis in rats and to elucidate the possible mechanism by which juglanin might recover it. Fructose-feeding rats were orally administrated with juglanin of 5, 10 and 20 mg/kg for 6 weeks, respectively. Juglanin exerted prevention of fructose-feeding-stimulated increased LPS levels, accelerated alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) and up-regulated inflammatory cytokines expression in serum, mainly including tumor necrosis factor-alpha (TNF-a), Interleukin 1beta (IL-1β), Interleukin 6 (IL-6) and Interleukin 18 (IL-18). Meanwhile, toll-like receptor 4 (TLR4)-modulated mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) and apoptosis-related Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway are involved in the progression of hepatic injury and inflammation. And juglanin was found to suppress fructose-feeding-induced activation of these signaling pathways compared with the model group administrated only with fructose. These results indicate that juglanin represses inflammatory response and apoptosis via TLR4-regulated MAPK/NF-κB and JAK2/STAT3 signaling pathway respectively in rats with hepatitis induced by LPS for fructose-feeding. Treatment of juglanin might be an effective therapeutic strategy for preventing hepatitis. [ABSTRACT FROM AUTHOR]

Forsythiaside A, an active constituent isolated from air-dried fruits of Forsythia suspensa , has been reported to have multiple pharmacological activities including anti-inflammatory, anti-oxidant, and antioxidant activities. In the present study, the hepatoprotective effect of forsythiaside A was investigated in lipopolysaccharide (LPS)/ d -galactosamine (GalN)-induced acute liver injury in mice. Mice acute liver injury model was induced by LPS (50 μg/kg)/GalN (800 mg/kg). Forsythiaside A was administrated 1 h prior to LPS/GalN exposure. The results showed that forsythiaside A attenuated hepatic pathological damage, malondialdehyde (MDA) content, and serum ALT, and AST levels induced by LPS/GalN. Moreover, forsythiaside A inhibited NF-κB activation, serum TNF-α and hepatic TNF-α levels induced by LPS/GalN. Furthermore, we found that forsythiaside A up-regulated the expression of Nrf2 and heme oxygenase-1. Our results showed that forsythiaside A protected against LPS/GalN-induced liver injury through activation of Nrf2 and inhibition of NF-κB activation. [ABSTRACT FROM AUTHOR]

Mangiferin, a glucosylxanthone from Mangifera indica , has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury. Mangiferin was given 1 h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1β, TNF-α, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1β and TNF-α production in LPS-stimulated primary hepatocytes. Mangiferin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. Furthermore, mangiferin inhibited LPS/ d -GalN-induced hepatic NLRP3, ASC, caspase-1, IL-1β and TNF-α expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]