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ABSTRACT: Infection with hepatitis B virus (HBV) continues to be a major global cause of acute and chronic liver disease with high mortality. Herein, we examined both the anti-HBV and hepatoprotective activity of α-DDB-FNC. In human HBV-transfected liver cell line HepG2.2.15, α-DDB-FNC effectively suppressed the secretion of HBV antigens in a time and dose-dependent manner with 25.11% inhibition on HBeAg and 43.68% on HBsAg at 2.5 μM on day 9. Consistent with the HBV antigen reduction, α-DDB-FNC (2.5 μM) also reduced HBV DNA level by 77.74% extracellularly and 78.94% intracellularly on day 9. In the duck hepatitis B virus (DHBV) infected ducks, after α-DDB-FNC was given once daily for 10 days, the serum and liver DHBV DNA levels were reduced markedly with 96.81% and 97.21% at 10 mg•kg(-1) on day 10, respectively. In Con A-induced immunological liver-injury mice, α-DDB-FNC significantly inhibited the elevation of serum ALT, AST, TBiL and liver MDA, NO levels. Furthermore, significant improvement of the liver was observed after α-DDB-FNC treatment both in ducks and mice, as evaluated by the histopathological analysis. In conclusion, our results demonstrated that α-DDB-FNC possesses both antiviral activity against HBV and hepatoprotective effect to Con A -induced liver-injury mice.
Antiviral research 10/2012; · 3.61 Impact Factor
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ABSTRACT: BACKGROUND: Hepatitis B virus (HBV) infection causes major public health problems worldwide. The clinical limitation of current antiviral drugs for HBV, such as lamivudine, is causing rapid emergence of drug-resistant viral strains during prolonged antiviral therapy. Therefore, new antiviral drugs are urgently needed to prevent or delay the selection of drug-resistant HBV mutants. A novel cytidine analogue, FNC (2'-deoxy-2'-β-fluoro-4'-azidocytidine), was recently shown to strongly inhibit human HBV and duck HBV (DHBV) replication in vitro and in vivo, respectively. The present study was designed to evaluate the in vitro antiviral activity of FNC against clinical wild-type and lamivudine-resistant HBV isolates in transiently transfected cells. METHODS: HBV DNA was extracted from serum samples collected both before lamivudine therapy and at the time of viral breakthrough and was amplified by polymerase chain reaction (PCR). The amplicon was cloned into a novel expression vector, pHY106, which can initiate the intracellular HBV replication cycle after cell transfection. Following transfection of the cloned amplicon into HepG2 cells, a drug susceptibility assay was performed. Quantitative real-time PCR was used for determining the amount of intracellular HBV DNA, and the effective concentration required to reduce HBV replication by 50% (EC(50)) was calculated. RESULTS: FNC inhibited the replication of both wild-type and lamivudine-resistant HBV clinical isolates in a dose-dependent manner, with EC(50) values of 0.12 ± 0.01 μM and 0.27 ± 0.01 μM, respectively. CONCLUSIONS: FNC is a potential antiviral agent against both wild-type and lamivudine-resistant HBV clinical isolates, therefore deserves further evaluation for the treatment of HBV infection.
Antiviral therapy 08/2012; · 3.16 Impact Factor
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Xiaoyan Wang,
Yafeng Wang,
Zhe Ren,
Chuiwen Qian,
Yicheng Li, Qingduan Wang,
Yan Zhang,
Liyun Zheng,
Jinhua Jiang,
Chongren Yang,
Dong Wang,
Yingjun Zhang,
Jianglin Fan,
Yifei Wang
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ABSTRACT: Coxsackievirus B3 (CVB3) is a dominant causative agent for viral myocarditis. So far, effective therapies for the treatment of the disease are not available. 20(S)-Protopanaxtriol is a major component of Panax pseudoginseng and has been clinically used for the treatment of heart diseases. However, it is not known whether 20(S)-protopanaxtriol exerts any anti-viral effects. Thus, the aim of this study was to investigate the therapeutic effects of 20(S)-protopanaxtriol against CVB3 in vivo and in vitro.
The antiviral effects of 20(S)-protopanaxtriol in vitro were evaluated in HeLa cells infected by CVB3. Then, we examined the protective effects of 20(S)-protopanaxtriol on CVB3-induced myocarditis in BALB/c mice. These mice were treated with 20(S)-protopanaxtriol at doses of 100-400 mg·kg(-1)·day(-1) for 7 days and compared with the controls.
We found that 20(S)-protopanaxtriol possessed potent antiviral effects on CVB3 in vitro. Compared with control mice, virus titers and pathological changes in the hearts were significantly decreased in the 20(S)-protopanaxtriol-treated group. Furthermore, biochemical markers of myocardial injury such as plasma lactate dehydrogenase and creatine kinase were decreased to normal levels.
These data provide the possibility that 20(S)-protopanaxtriol can be used as a potential therapeutic means for treatment of viral myocarditis.
Pathobiology 06/2012; 79(6):285-9. · 1.18 Impact Factor
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Liyun Zheng,
Qiang Wang,
Xiaorui Yang,
Xiaohe Guo,
Lu Chen,
Le Tao,
Lihong Dong,
Yujiang Li,
Haoyun An,
Xuejun Yu, Qingduan Wang,
Junbiao Chang
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ABSTRACT: New drugs are needed to combat HBV infection. We investigated the anti-HBV activity of the deoxycytidine analogue FNC, which has anticancer activity and has been found to inhibit HCV replication.
In this study, a human hepatoma HepG2.2.15 cell culture system and duck HBV (DHBV) infection model were used as the in vitro and in vivo models to evaluate the anti-HBV activity of FNC.
In the cell model, FNC effectively suppressed the secretion of the HBV antigens in a dose-dependent manner, with 50% effective concentration values of 0.037 μM for hepatitis B surface antigen and 0.044 μM for hepatitis B e antigen on day 9. Consistent with the HBV antigen reduction, FNC also reduced the HBV DNA level by 92.31% and 93.90% intracellularly and extracellularly, respectively. DHBV DNA levels were markedly reduced after treatment with the FNC at 0.5, 1.0 and 2.0 mg/kg•day dosages. The inhibition rate of FNC at the dose of 2.0 mg/kg•day reached 91.68% and 81.96%, in duck serum and liver, respectively, on day 10. Furthermore, significant liver histology restoration after FNC treatment was observed, as evaluated by the histopathological analysis.
FNC can evidently inhibit the replication of HBV in the HepG2.2.15 cell line in vitro and inhibits DHBV replication in ducks in vivo. It could be potentially developed into a new anti-HBV drug.
Antiviral therapy 03/2012; 17(4):679-87. · 3.16 Impact Factor
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Yu-Bing Zhou,
Ya-Feng Wang,
Yan Zhang,
Li-Yun Zheng,
Xiao-Ang Yang,
Ning Wang,
Jin-Hua Jiang,
Fang Ma,
De-Tao Yin,
Chang-Yu Sun, Qing-Duan Wang
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ABSTRACT: Hepatitis B virus (HBV) infection causes major public health problems worldwide. The clinical limitation of current antiviral drugs for HBV, such as lamivudine, is the emergence of drug-resistant viral strains during prolonged antiviral therapy. Cepharanthine hydrochloride (CH), a natural alkaloid-derived compound, has been reported to possess potent activity against various viruses. The present study was performed to evaluate the in vitro activity of CH against clinical wild-type and lamivudine-resistant HBV isolates in transiently transfected cells. HBV DNA was extracted from serum samples collected both before lamivudine therapy and at the time of viral breakthrough and was amplified by polymerase chain reaction (PCR). The amplicons were cloned into a novel expression vector, pHY106, which can initiate the intracellular HBV replication cycle after cell transfection. Following transfection of the cloned amplicon into HepG2 cells, a drug susceptibility assay was performed. The level of viral antigen, HBeAg, was determined by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR (Q-PCR) was used for determining the amount of intracellular HBV DNA. Heat stress cognate 70 (Hsc70), a host protein required for HBV replication, was also analyzed by reverse transcription PCR (RT-PCR) to explore the possible antiviral mechanism of CH. The results showed that CH inhibited replication and HBeAg production by either wild-type or lamivudine-resistant HBV clinical isolates in a dose-dependent manner. The Hsc70 mRNA was also downregulated significantly. In conclusion, CH is active against both wild-type and lamivudine-resistant HBV clinical isolates, and its activity may be associated with its inhibition of host Hsc70.
European journal of pharmacology 02/2012; 683(1-3):10-5. · 2.59 Impact Factor
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Qiang Wang,
Xiaobing Liu, Qingduan Wang,
Yan Zhang,
Jinhua Jiang,
Xiaohe Guo,
Qingxia Fan,
Liyun Zheng,
Xuejun Yu,
Ning Wang,
Zhenliang Pan,
Chuanjun Song,
Wenqing Qi,
Junbiao Chang
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ABSTRACT: Inhibition of cellular DNA synthesis is a strategy to block cancer cell division. Nucleoside analogues can incorporate into DNA and terminate DNA strand elongation. So far, several nucleoside analogues have been successfully used as anticancer drugs. FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine is a novel cytidine analogue which demonstrated potent activity against hepatitis C virus (HCV). To investigate the therapeutic potential of FNC in human cancers we studied its activity in a number of cancer cells in vitro and in vivo. FNC potently inhibited cell proliferation with an IC(50) of 0.95-4.55μM in a variety of aggressive human cancer cell lines including B-cell non-Hodgkin's lymphomas, lung adenocarcinoma and acute myeloid leukemia. Cells treated with FNC exhibited G1 and S cell cycle arrest at high and low dose, respectively, which confirms the mechanism of action of nucleoside analogues. Treatment of B-NHL cell lines with FNC induced apoptosis in a dose and time dependent manner. Finally, mouse xenograft models of hepatocarcinoma (H22), sarcoma (S180) and gastric carcinoma (SGC7901) demonstrated that FNC had significant tumor growth inhibition activity in a dose-dependent manner with low toxicity. Together, our results suggest that FNC may be a valuable therapy in cancer patients and warrant early phase clinical trial evaluation.
Biochemical pharmacology 01/2011; 81(7):848-55. · 4.25 Impact Factor
