Shikonin protects against D-Galactosamine and lipopolysaccharide-induced acute hepatic injury by inhibiting TLR4 signaling pathway.

Shikonin, a naphthoquinone isolated from the root of medical herb Lithospermum erythrorhizon, has been reported to have anti-inflammatory effect. However, there is no related research for the treatment of shikonin on hepaic injury. The purpose of this study was to investigate the effects of shikonin on D-Galactosamine and Lipopolysaccharide-induced hepatic injury in mice. Male BALB/c mice were pretreated with shikonin 1 h before LPS/D-GalN treatment. The pathological changes of hepatic injury were detected by H&E staining. The levels of TNF-α and IL-1ß in hepatic tissues were detected by ELISA. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured in this study. In addition, the expression of TLR4 and NF-κB were determined by western blot analysis. These results suggest that shikonin effectively prevents LPS/D-GalN-induced liver injury by inhibiting AST and ALT levels, as well as inflammatory cytokines TNF-α and IL-1ß production. The expression of TLR4 and NF-κB activation induced by LPS/D-GalN were also inhibited by treatment of shikonin. In vitro, shikonin significantly inhibited LPS-induced TNF-α and IL-1ß production, as well as TLR4 expression and NF-κB activation. In conclusion, the results of the present study suggest that shikonin attenuates LPS/D-GalN-induced hepatic injury by inhibiting TLR4 signaling pathway.

The protective effect of juglanin on fructose-induced hepatitis by inhibiting inflammation and apoptosis through TLR4 and JAK2/STAT3 signaling pathways in fructose-fed rats.

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 20mg/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-1ß), 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.

Neoalbaconol inhibits cell growth of human cholangiocarcinoma cells by up-regulating PTEN.

The recently isolated small-molecule neoalbaconol (NA) from Albatrellus confluens has been suggested to possess the ability to inhibit cell growth of many cancer cells. In this study, we investigated the role of NA in the regulation of cell apoptosis in human cholangiocarcinoma cell lines both in vitro and in vivo. Our results indicate that NA could induce cancer cell death via the AKT pathway by targeting phosphorate and tension homolog detected on chromosome 10 (PTEN) and supported the feasibility of NA being a novel chemotherapeutic treatment for human cholangiocarcinoma.

Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

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 1h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1ß, TNF-α, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1ß 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-1ß and TNF-α expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

Protective effect of forsythiaside A on lipopolysaccharide/d-galactosamine-induced liver injury.

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 (50µg/kg)/GalN (800mg/kg). Forsythiaside A was administrated 1h 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.