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This study examined the effect of Asiatic acid from Potentilla chinensis (AAPC) on chronic ethanolinduced hepatic injury. Rats underwent intragastric administration of ethanol (5.0-9.0 g/kg) once a day for 12 weeks. A subset of rats were also intragastrically treated with AAPC (2, 4 or 8 mg/kg) once a day. In the end, AAPC treatment significantly protected against ethanol-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases levels and the attenuation of histopathological changes in rats. Additionally, AAPC significantly decreased blood alcohol and acetaldehyde concentrations by enhancing alcohol dehydrogenase and aldehyde dehydrogenase activities. Mechanistically, studies showed that AAPC remarkably alleviated the formations of malondialdehyde and myeloperoxidase, restored impaired antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase, and inhibited cytochrome P450 (CYP)2E1 activity. Moreover, the over-expression of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the elevated plasma endotoxin level and the up-regulated Toll-like receptor 4 (TLR4), CD14 and myeloid differentiation factor 88 (MyD88) as well as nuclear factor-κB were also suppressed by AAPC in ethanol-intoxicated rats. In conclusion, the protective effect of AAPC on ethanol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress and inhibit Kupffer cell activation by decreasing the level of plasma endotoxin and the expression of TLR4, CD14 and MyD88.

Infection with hepatitis B virus (HBV) is the most common cause of liver disease worldwide. However, because the current interferon (IFN)-based treatments have toxic side effects and marginal efficacy, improved antivirals are essential. Here we report that unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) from the HBV genome (HBV-CpG) induced robust expression of IFN-a by plasmacytoid dendritic cells (pDCs) in a Toll-like receptor 9 (TLR9)-dependent manner. We also identified inhibitory guanosine-rich ODNs in the HBV genome (HBV-ODN) that are capable of inhibiting HBV-CpG-induced IFN-a production. Furthermore, nanoparticles containing HBV-CpG, termed NP(HBV-CpG), reversed the HBV-ODN-mediated suppression of IFN-a production and also exerted a strong immunostimulatory effect on lymphocytes. Our results suggest that NP(HBV-CpG) can enhance the immune response to hepatitis B surface antigen (HBsAg) and skew this response toward the Th1 pathway in mice immunized with rHBsAg and NP(HBV-CpG). Moreover, NP(HBV-CpG)-based therapy led to the efficient clearance of HBV and induced an anti-HBsAg response in HBV carrier mice. Conclusion: Endogenous HBV-CpG ODNs from the HBV genome induce IFN-a production so that nanoparticle-encapsulated HBV-CpG may act as an HBsAg vaccine adjuvant and may also represent a potent therapeutic agent for the treatment of chronic HBV infection. (HEPATOLOGY 2014;59:385-394) P ersistent infection with the hepatitis B virus (HBV) affects more than 360 million people worldwide and has become a severe public health problem owing to the increased risk of liver cirrhosis and hepatocellular carcinoma in infected individuals. The current recombinant hepatitis B surface antigen (rHBsAg) vaccine provides protection against HBV infection but fails to protect 10% of those who are vaccinated and is also ineffective for individuals who are already infected with HBV. Conventional antiviral drugs used for the treatment of HBV, including lamivudine and interferon-alpha (IFN-a), suppress viral replication and reduce hepatic symptoms. 1 However, the persistence of HBV covalently closed circular DNA (cccDNA) and defective immune responses lead to treatment failure and progression to liver disease. 2 Therefore, more efficient therapeutic strategies are needed to eradicate HBV infection.HBV seems to avoid inducing strong innate immune responses including the type I IFN response. 2 Therefore, methods of inducing vigorous immune responses against HBV may play a critical role in the clearance of HBV infection. The unmethylated cytosine-phosphate-guanosine (CpG) motifs presented in bacterial DNA can stimulate the immune system by interacting with the pattern-recognition receptor Tolllike receptor 9 (TLR9). 3 TLR9 is predominantly expressed in plasmacytoid dendritic cells (pDCs) and

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