Control mice were treated with an equal volume of CMC-Na

Control mice were treated with an equal volume of CMC-Na. in liver regeneration by increasing RAC3 IL-1Ra which acts as an Acute-Phase Protein (APP). In addition, a lethal CCl4-induced acute liver failure model offers a survival benefit in oroxylin A treated WT mice. However, oroxylin A could not significantly improve the percent survival of IL-1RI?/? mice with a lethal CCl4-induced acute liver failure. Conclusions Our study confirmed that oroxylin A could strongly promote liver structural remodeling and functional recovery through IL-1Ra/IL-1RI signaling pathway. All these results support the possibility of oroxylin A being a therapeutic candidate for acute liver injury. Introduction The liver is a very important organ which regulates the balance of metabolic homeostasis, moreover, it has an amazing regenerative capability after liver injury [1], [2]. CCl4-induced acute hepatic injury widely used for studying liver regeneration [3], [4]. The hepatotoxicity of CCl4 specially causes oxidative stress and membrane damage [5], then lipid MG-101 peroxidation induces hepatocellular damage and enhances inflammation. Hepatitis is fulminated within few hours after CCl4 treatment, which specifically leads to necrosis [6], [7]. Oroxylin A (5, 7-Dihydroxy-6-methoxyflavone, C16H12O5, Fig. 1A ) is a flavonoid isolated from and was measured and remained constant during the experimental conditions in this study. Table 1 Primer sequences used for real-time quantitative PCR. test (unpaired, two-tailed) was used for comparisons between data from specified different conditions. Results from survival experiments were analyzed using the log-rank test and presented MG-101 as Kaplan-Meier survival curves. Results Oroxylin A Protects Mice Against Acute Hepatocellular Damage To confirm the role of oroxylin A in protecting mice against hepatic damage, we used MG-101 serum ALT, AST and Albumin as indicators for liver injury. After CCl4 treatment, serum ALT and AST rapidly elevated to peak level at day 1, then decreased thereafter, while oroxylin A treatment significantly inhibited the elevation of serum ALT and AST from day 1 to day 5 ( Fig. 2A and B ). The attenuated increasing of serum AST and ALT indicated that oroxylin A has a directly protective role on hepatocytes. Serum Albumin level is also considered as a very classical indicator for evaluating functional recovery of injured liver. In our study, we found that serum Albumin significantly increased after oroxylin A administration compared to the control ( Fig. 2C ). To evaluate the effects of oroxylin A on hepatocellular necrosis and inflammation, histological changes in the liver after CCl4 treatment with or without oroxylin A administration were examined by hematoxylin-eosin staining. Liver sections from the oroxylin A administrated mice demonstrated only moderate necrosis involving the centrilobular areas, maintaining a rather normal architecture, the necrotic areas were significantly diminished around the MG-101 central vein and centrilobular regions at day 3 after CCl4 treatment ( Fig. 2D, E and F ). These data together clealy indicated that Oroxylin A has potential anti-hepatotoxic activity. Open in a separate window Figure 2 Oroxylin A protects liver against CCl4-induced acute liver injury.Mice were treated with CCl4 (1 ml/kg body weight and 13 diluted in corn oil) to induce acute liver injury, then orally administered oroxylin A (60 mg/kg body weight and diluted in CMC-Na) 1 hour after CCl4 injection, once per day for 4 days. Control mice were treated with an equal volume of CMC-Na. Subsequently, serum ALT, AST and Albumin were measured at indicated time points and determined as described in materials and methods. (A) Serum MG-101 alanine aminotransferase (ALT). (B) Serum aspartate aminotransferase (AST). (C) Serum Albumin. (D) Percentage of necrotic areas in oroxylin A groups were calculated at day 2 and day 3 after CCl4 treatment. (E) Representative liver section of control group was stained with hematoxylin and eosin (HE) at day 3 after CCl4 treatment, which shows partial necrosis with clusters of inflammatory cells around central vein. (F) Representative HE stained liver section of oroxylin A administration at day 3 after CCl4 treatment, which demonstrates.