The variables hemoglobin and albumin 3-deazaneplanocin A price may explain the lower miR-122 levels identified in HIV infection, as HIV is known to cause anemia and has been associated with under-nutrition (HIV co-infected serum had lower median values for both hemoglobin and albumin, though not significantly). Additionally, the absence of an association between miR-122 and cirrhosis suggests that care must be taken when evaluating miR-122, as it may be influenced by factors distinct from liver injury. Disclosures: Mamta K. Jain – Advisory Committees or Review Panels:

Merck, Vertex, Boehringer Ingelheim ; Grant/Research Support: Vertex, Bristol-Myers Squibb, Pfizer, Janssen, Gilead, Boehrnger Ingelheim , Viiv Healthcare, EMD Serono William M. Lee-Consulting: Eli Lilly, Novartis; Grant/Research Support: Gilead, Roche, Vertex, BI, Anadys, BMS, merck; Speaking and Teaching: Merck The following people have nothing to disclose: Perry H. Dubin The natural alkaloid berberine (BRB) is commonly used as a supplement in the US, and has been shown to possess a wide range of pharmacological and biochemical effects, including protection against liver injury. In this study, we analyzed the effects of BRB in different murine models of liver injury, and investigated the

underlying mechanism of action. BRB (5 mg/kg i.p.) was tested in steatohepatitis induced by administration of a methionine and choline deficient (MCD) diet selleck compound and in acute acetaminophen (APAP) intoxication. The mechanism of action of BRB was further investigated 上海皓元医药股份有限公司 in LPS-stimulated murine macrophages (RAW 264.7) in vitro. Activation of the P2X7 receptor was assessed by measurement of calcium transients. BRB markedly suppressed ALT elevation and necroinflammation in MCD-fed mice. In addition, intrahepatic gene expression of CD11 b, CCL2, TGF-b, type I procollagen, andTNF were significantly downregulated in MCD-fed, BRB-treated mice. Feeding a MCD diet increased hepatic levels of mature IL-1 β and expression of all components of the NALP3 inflammasome pathway,

while these effects were limited by BRB. Surprisingly, administration of BRB to MCD-fed mice caused an excess of mortality, which could not be attributed to increased serum levels of BRB, measured by LC/MS mass spectrometry. In the model of APAP-induced hepatotoxicity, pretreatment with BRB reduced ALT elevation. Moreover, upregulation of the expression of NALP3 inflammasome components induced by APAP was limited by BRB, which also reduced mortality. Inflammasome activation in LPS-stimulated RAW 264.7 was markedly decreased by BRB, demonstrating a direct interference with activation of the inflammasome pathway. BRB did not affect the activation of NF-κB pathway, which provides an initial signal leading to inflammasome activation. However, exposure of RAW 264.