RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Formula Le-Cao-Shi (LCS) is a traditional Chinese medicine (TCM), which has long been used as a folk remedy against hepatitis B in China. The present study was conducted to evaluate the anti-hepatitis B effects of aqueous extract of LCS in vivo and in vitro. MATERIALS AND METHOD: we investigated the anti-HBV effects of LCS in vivo and in vitro with duck hepatitis B model and HepG2.2.15â¯cell line model, respectively. The serologic and cellular biomarkers and the histopathological changes were examined. RESULTS: By a duck hepatitis B model, the extract of LCS was found to restrain the expressions of duck hepatitis B surface antigen (DHBsAg), hepatitis B e antigen (DHBeAg), and HBV-DNA (DHBV-DNA). Moreover, LCS could decrease the levels of aspartate and alanine aminotransferases (AST and ALT) and ameliorate duck liver histological lesions. Correspondingly, in a HepG2.2.15 cellular model, LCS could also significantly inhibit the secretions of HBsAg and HBeAg. CONCLUSION: LCS exerted potent anti-hepatitis effects against the infection of HBV. The above results demonstrated the first-hand experimental evidences for the anti-hepatitis B efficiency of LCS. Our study provides a basis for further exploration and development of this promising compound prescription to treat hepatitis B disease.
Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B/tratamento farmacológico , Hepatite Viral Animal/tratamento farmacológico , Animais , Antivirais/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA Viral , Patos , Hepatite B/imunologia , Hepatite B/patologia , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B do Pato/genética , Vírus da Hepatite B do Pato/imunologia , Antígenos E da Hepatite B/imunologia , Hepatite Viral Animal/imunologia , Hepatite Viral Animal/patologia , Hepatite Viral Animal/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Medicina Tradicional ChinesaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Acanthus ilicifolius L. is an important medicinal mangrove plant. It is popularly used for its anti-inflammatory, antioxidant activity and hepatoprotective effects. The present study was conducted to evaluate the effect of treatment with alcohol extract of Acanthus ilicifolius L. on duck hepatitis B. MATERIALS AND METHODS: One-day-old Guangxi shelducks injected intraperitoneally with strong positive duck hepatitis B virus (DHBV) serum were used to establish a duck hepatitis B animal model in the study. The ducks were respectively administered in different groups with low-, middle- and high-dose alcohol extracts of Acanthus ilicifolius L., the positive control drug acyclovir (ACV) and double-distilled water. The levels of serum DHBV DNA were detected by fluorescence quantitative PCR (FQ-PCR). Duck hepatitis B surface antigen (DHBsAg) and duck hepatitis B e antigen (DHBeAg) OD values in the serum were measured by ELISA. The activity of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) in the serum was measured, and the livers were taken for histopathological examination. RESULTS: The levels of serum DHBV DNA and the values of DHBsAg and DHBeAg OD were not significant in any of the dose extract groups. However, the ALT activity was obviously lower in the middle- and high-dose extract groups. It was also found that a high dose of alcohol extract could reduce the activity of AST significantly and significantly improve hepatic pathological effects. CONCLUSIONS: High-dose alcohol extract of Acanthus ilicifolius L. has an obvious protective effect on the liver function and liver tissue. However, the present study finds that Acanthus ilicifolius L. cannot inhibit the replication of duck hepatitis B virus.
Assuntos
Acanthaceae/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Infecções por Hepadnaviridae/tratamento farmacológico , Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite Viral Animal/tratamento farmacológico , Fígado/efeitos dos fármacos , Fitoterapia , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Alanina Transaminase/sangue , Animais , Animais Recém-Nascidos , Antivirais/farmacologia , Antivirais/uso terapêutico , Aspartato Aminotransferases/sangue , DNA Viral/sangue , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Patos , Infecções por Hepadnaviridae/patologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite Viral Animal/patologia , Fígado/patologia , Carga Viral/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Nirtetralin B, a new lignan first reported by our team, is isolated from Phyllanthus niruri L. This plant has long been used in folk medicine for liver protection and antihepatitis B in many Asian countries. This study was designed to evaluate the anti-hepatitis B virus activity of nirtetralin B using HepG2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models. MATERIALS AND METHODS: Nirtetralin B was isolated from Phyllanthus niruri L. (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hepatitis B virus activity was evaluated both in vitro and in vivo. The human HBV-transfected liver cell line HepG2.2.15 was used in vitro assay. And the in vivo anti-hepatitis B virus activity was evaluated on the expression of HBV replication, HBsAg, HBeAg, ALT and AST on day 0, 7, 14, 17 after nirtetralin B was dosed intragastricly (i.g.) once a day for 14 days at the dosages of 25, 50 and 100mg/kg/day in the duck hepatitis B virus (DHBV) infected ducks. RESULTS: In the human HBV-transfected liver cell line HepG2.2.15, nirtetralin B effectively suppressed the secretion of the HBV antigens in a dose-dependent manner with IC50 values for HBsAg of 17.4µM, IC50 values for HBeAg of 63.9µM. In DHBV-infected ducklings, nirtetralin B significantly reduced the serum DHBV DNA, HBsAg, HBeAg, ALT and AST. And analysis of the liver pathological changes confirmed the hepatoprotective effect of nirtetralin B. CONCLUSION: The experimental data demonstrated that nirtetralin B exhibits anti-hepatitis B virus activity both in vitro and in vivo.
Assuntos
Anisóis/farmacologia , Antivirais/farmacologia , Dioxóis/farmacologia , Hepatite B/tratamento farmacológico , Lignanas/farmacologia , Phyllanthus/química , Animais , Anisóis/administração & dosagem , Anisóis/isolamento & purificação , Antivirais/administração & dosagem , Antivirais/isolamento & purificação , Dioxóis/administração & dosagem , Dioxóis/isolamento & purificação , Relação Dose-Resposta a Droga , Patos , Feminino , Células Hep G2 , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B do Pato/efeitos dos fármacos , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Lignanas/administração & dosagem , Lignanas/isolamento & purificação , Masculino , Medicina Tradicional , Replicação Viral/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Niranthin is a lignan isolated from Phyllanthus niruri L. This plant has long been used in folk medicine for liver protection and antihepatitis B in many Asian countries. This study was designed to evaluate the anti-hepatitis B virus activity of niranthin using HepG2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models. MATERIALS AND METHODS: Niranthin was isolated from Phyllanthus niruri L. (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hepatitis B virus activity was evaluated both in vitro and in vivo. The human HBV-transfected liver cell line HepG2.2.15 was used in vitro assay. And the in vivo anti-hepatitis B virus activity was evaluated on the expression of HBV replication, HBsAg, HBeAg, ALT and AST on day 0, 7, 14, 17 after niranthin was dosed intragastricly (i.g.) once a day for 14 days at the dosages of 25, 50 and 100 mg/kg/day in the duck hepatitis B virus (DHBV) infected ducks. RESULTS: In the human HBV-transfected liver cell line HepG2.2.15, the secretion of HBsAg and HBeAg were significantly decreased after treatment with niranthin for 144 h, with IC50 values for HBsAg of 15.6 µM, IC50 values for HBeAg of 25.1 µM. In DHBV-infected ducklings, niranthin significantly reduced the serum DHBV DNA, HBsAg, HBeAg, ALT and AST. Furthermore, analysis of the liver pathological changes confirmed the hepatoprotective effect of niranthin. CONCLUSION: The experimental data demonstrated that niranthin exhibits anti-hepatitis B virus activity both in vitro and in vivo.
Assuntos
Anisóis/farmacologia , Antivirais/farmacologia , Dioxóis/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Phyllanthus/química , Animais , Anisóis/administração & dosagem , Anisóis/isolamento & purificação , Antivirais/administração & dosagem , Antivirais/isolamento & purificação , Dioxóis/administração & dosagem , Dioxóis/isolamento & purificação , Modelos Animais de Doenças , Patos , Feminino , Células Hep G2 , Infecções por Hepadnaviridae/tratamento farmacológico , Infecções por Hepadnaviridae/virologia , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B do Pato/efeitos dos fármacos , Antígenos E da Hepatite B/metabolismo , Hepatite Viral Animal/tratamento farmacológico , Hepatite Viral Animal/virologia , Humanos , Concentração Inibidora 50 , Lignanas/administração & dosagem , Lignanas/isolamento & purificação , Lignanas/farmacologia , MasculinoRESUMO
In order to validate the antiviral effect against hepatitis B virus (HBV) of Taraxacum mongolicum (T. mongolicum), the protective effect on hepatocytes, and antiviral properties against duck hepatitis B virus (DHBV) and HBV of T. mongolicum extract (TME) were evaluated in chemically-injured neonatal rat hepatocytes, DHBV-infected duck fetal hepatocytes and HBV-transfected HepG2.2.15 cells, respectively. The results demonstrated that TME at 50-100 µg/ml improved D-galactosamine (D-GalN), thioacetamide (TAA) and tert-butyl hydroperoxide (t-BHP)-injured rat hepatocytes, and produced protection rates of 42.2, 34.6 and 43.8% at 100 µg/ml, respectively. Furthermore, TME at 1-100 µg/ml markedly inhibited DHBV DNA replication. Additionally, TME at 25-100 µg/ml reduced HBsAg and HBeAg levels and produced inhibition rates of 91.39 and 91.72% at 100 µg/ml, respectively. TME markedly inhibited HBV DNA replication at 25-100 µg/ml. The results demonstrate the potent antiviral effect of T. mongolicum against HBV effect. The protective of TME effect on hepatocytes may be achieved by its ability to ameliorate oxidative stress. The antiviral properties of TME may contribute to blocking protein synthesis steps and DNA replication. Furthermore, major components of TME were quantificationally analyzed. These data provide scientific evidence supporting the traditional use of TME in the treatment of hepatitis.
Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Hepatite B/fisiologia , Hepatócitos/virologia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Animais Recém-Nascidos , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Patos , Galactosamina , Glucosídeos/química , Glucosídeos/farmacologia , Células Hep G2 , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B do Pato/fisiologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Luteolina/química , Luteolina/farmacologia , Ratos , Ratos Sprague-Dawley , Tioacetamida , terc-Butil HidroperóxidoRESUMO
Traditional Chinese herbal medicine (TCHM) has been widely used in the treatment of chronic hepatitis B (CHB) in China. The systematic analysis of clinical research of TCHM against CHB revealed its potential but not confirmed its therapeutic effect. To understand the detailed antiviral effect of TCHM against HBV infection, we systematically analysed the anti-HBV effect of individual Chinese herbs on the basis of the research on individual TCHM in vitro and in vivo, which were published from 1995 to 2012. Among 171 herbal components isolated from 76 Chinese herbs, we found 13 compounds and 9 extracts isolated from 18 Chinese herbs showing strong inhibitory effect on HBV DNA, HBeAg or HBsAg release with low cytotoxicity in HepG2.2.15 cells, and agents from 12 Chinese herbs showing the highest inhibition rates of plasma DHBV DNA of more than 50% in DHBV-infected ducks. In addition, the two compounds chrysophanol 8-O-beta-D-glucoside isolated from Rheum palmatum and wogonin isolated from Scutellaria baicalensis were found to display strong anti-HBV activity. Interestingly, compounds isolated from 5 of these effective anti-HBV Chinese herbs were found to show strong antibacterial or antifungal activity also. This review summarizes and analyses the studies on the anti-HBV effect of individual TCHM in cell and animal models, providing potential perspective in the understanding of TCHM in the treatment of hepatitis B and the development of new anti-HBV drugs from TCHM.
Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Infecções por Hepadnaviridae/veterinária , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Hepatite Viral Animal/tratamento farmacológico , Medicina Herbária/métodos , Animais , Antivirais/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Patos , Infecções por Hepadnaviridae/tratamento farmacológico , Infecções por Hepadnaviridae/virologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hepatite Viral Animal/virologia , Humanos , Testes de Sensibilidade Microbiana , Plantas Medicinais/químicaRESUMO
BACKGROUND & OBJECTIVES: Destruxin A, destruxin B and destruxin E isolated from entomopathogenic fungus Metarhizium anisopliae showed a strong suppressive effect on the replication of hepatitis B virus (HBV) in human hepatoma cells. In this study, the anti-HBV effects of the crude destruxins extracted from M. anisopliae var. dcjhyium were detected both in vitro and in vivo. METHODS: HepG2.2.15 cells were cultured to observe the inhibitory effects of the crude destruxins on the gene expression and replication of HBV by radioimmunoassay detection and real-time quantitative PCR. In vivo, duck HBV (DHBV)-infected ducks were treated with the crude destruxins at 2.0, 4.0, 6.0 µg/kg once a day for 15 days, DHBV DNA was examined by real-time quantitative PCR. RESULTS: The crude destruxins suppressed the replication of HBV-DNA and the production of HBsAg and HBeAg with IC 50 of about 1.2 and 1.4 µg/ml. Transcript of viral mRNA was significantly suppressed by the crude destruxins in HepG2.2.15 cells. In vivo, the duck serum DHBV-DNA levels were markedly reduced in the group of the crude destruxins. INTERPRETATION & CONCLUSIONS: The crude destruxins inhibited the gene expression and replication of HBV both in vitro and in vivo, and their anti-HBV effect was stronger than that with destruxin B. Our results indicate that the crude destruxins from M.anisopliae var. dcjhyium may be potential antivirus agents. Further studies need to be done to confirm these findings.
Assuntos
Depsipeptídeos/administração & dosagem , Proteínas Fúngicas/administração & dosagem , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Animais , DNA Viral/efeitos dos fármacos , Depsipeptídeos/isolamento & purificação , Patos/virologia , Proteínas Fúngicas/isolamento & purificação , Células Hep G2 , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B/genética , Humanos , Metarhizium , Extratos Vegetais/química , Replicação ViralRESUMO
It has been previously shown that Taraphochlamys affinis possessed anti-hepatitis B virus (HBV) activities. To identify the active ingredients, the total saponins (TSTA) were isolated from T. affinis and the inhibitory effect of TSTA on HBV in the duck HBV model was examined. The results showed that serum levels of DHBV-DNA decreased in all ducks treated with TSTA (1.0 and 2.0 g x kg(-1) x d(-1)) and lamivudine (3TC) (50 mg x kg(-1) x d(-1)) during treatment, but 7 days after the cessation of treatment (p7) with 3TC, the viral replication level returned to the pretreatment baseline. Contrariwise in ducks treated with TSTA, the effect of DHBV DNA inhibition lasted. Compared with model control group,the alanine aminotransferase (ALT), aspartate aminotransferase (AST) and duck hepatitis B surface antigen (DHBsAg) values of 1.0 and 2.0 g x kg(-1) x d(-1)-dose TSTA groups were significantly lower on 7, 14 days after the treatment (d7, d14) and p7, and at p7, the ALT and DHBsAg levels of 2.0 g x kg(-1) x d(-1)-dose TSTA group was significantly lower than that of 3TC group. Furthermore, significant histological improvement was noted in ducklings of TSTA treatment group 7 days after the withdrawal. The study results demonstrate that TSTA possesses potent anti-HBV activity.
Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Saponinas/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antígenos de Superfície/sangue , Antivirais/administração & dosagem , Antivirais/isolamento & purificação , DNA Viral/sangue , Medicamentos de Ervas Chinesas/isolamento & purificação , Infecções por Hepadnaviridae/tratamento farmacológico , Infecções por Hepadnaviridae/virologia , Vírus da Hepatite B do Pato/imunologia , Hepatite Viral Animal/tratamento farmacológico , Hepatite Viral Animal/virologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Saponinas/administração & dosagem , Saponinas/isolamento & purificaçãoRESUMO
OBJECTIVE: We have evaluated the direct effect of ampelopsis (APS) on duck hepatitis B virus (DHBV) replication in ducklings in vivo. METHOD: One-day-old ducklings were infected with DHBV. After infection for 7 days, the animals were treated with APS at dosages of 70, 150, 300 mg x kg(-1) of body weight via the oral route. The drug was given twice per day for 10 days continuously, and normal saline was used as control. The blood was drawn from the posterior tibial vein of all ducks before treatment (T0), after the medication for 5 (T5), 10 (T10) days and withdrawal of the drug for 3 days (P3). DHBV DNA in duck serum was detected by dot blot. RESULT: The duck serum DHBV-DNA levels were reduced in the group of APS (150, 300 mg x kg(-1)) after treated for 5 and 10 days and the levels of DHBV-DNA did not markedly relapse in both groups of APS after withdrawal of the drug for 3 days. We provide the first evidence that APS can efficiently inhibits DHBV replication in ducks in vivo. CONCLUSION: APS therefore warrants further investigation as a potential therapeutic agent for HBV infections.
Assuntos
Ampelopsis/química , Antivirais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Patos/virologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Animais , DNA Viral/metabolismo , Patos/sangue , Vírus da Hepatite B do Pato/metabolismo , Vírus da Hepatite B do Pato/fisiologia , Replicação Viral/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Jasminum officinale L. var. grandiflorum (JOG) is a folk medicine used for the treatment of hepatitis in south of China. Phytochemical studies showed that secoiridoid glycosides are the typical constituents of this plant. AIM OF THE STUDY: The present study was undertaken to evaluate the effect of oleuropein (Ole) derived from the flowers of JOG on hepatitis B virus (HBV) replication in HepG2 2.2.15 cell line in vitro and duck hepatitis B virus (DHBV) replication in ducklings in vivo. MATERIAL AND METHODS: The extracellular hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) concentrations in cell culture medium were determined by ELISA. DHBV in duck serum was analyzed by dot blot. RESULTS: Ole blocks effectively HBsAg secretion in HepG2 2.2.15 cells in a dose-dependent manner (IC(50)=23.2 microg/ml). Ole (80 mg/kg, intraperitoneally, twice daily) also reduced viremia in DHBV-infected ducks. CONCLUSION: Ole therefore warrants further investigation as a potential therapeutic agent for HBV infection.
Assuntos
Antivirais/farmacologia , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/efeitos dos fármacos , Hepatite Viral Animal/tratamento farmacológico , Jasminum/química , Extratos Vegetais/farmacologia , Piranos/farmacologia , Animais , Antivirais/uso terapêutico , Linhagem Celular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Patos , Flores , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B do Pato/fisiologia , Vírus da Hepatite B/fisiologia , Hepatite Viral Animal/sangue , Hepatite Viral Animal/virologia , Humanos , Glucosídeos Iridoides , Iridoides , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Piranos/uso terapêutico , Viremia/sangue , Viremia/tratamento farmacológico , Replicação Viral/efeitos dos fármacosRESUMO
Chinese herbs are widely used in the treatment of chronic viral hepatitis B. The effectiveness of 2 months' treatment with Astragali compound (AC), containing Radix Astragali and adjuvant components, was studied for the treatment of chronic viral hepatitis in 116 patients; 92 patients were given other drugs in regular clinical use for viral hepatitis (controls). The clinical efficacy of AC was significantly better in AC-treated patients than in controls. Negative seroconversions of hepatitis B virus (HBV) antigen e and HBV DNA were also significantly higher in AC-treated patients than in controls. Of eight duck viral hepatitis B models infected with duck hepatitis B virus (DHBV) and treated with AC, three showed negative seroconversion of DHBV DNA and serum DHBV DNA levels significantly decreased after AC administration compared with the controls; DHBV DNA was negative in biopsied liver tissue by in situ hybridization and immunohistochemistry in two ducks treated with AC. Pathological changes were milder in AC-treated ducks than in controls. These results indicate that AC may promote recovery from viral hepatitis and inhibit HBV replication.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite Viral Animal/tratamento farmacológico , Animais , DNA Viral/sangue , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite B Crônica/sangue , Hepatite Viral Animal/sangue , Humanos , Resultado do TratamentoRESUMO
AIMS: To evaluate the anti-hepatitis B virus (anti-HBV) effects and mechanisms of recombinant human serum albumin-interferon-alpha-2b fusion protein (rHSA-IFNalpha-2b) in vitro and in vivo. METHODS: The inhibiting effects on HBV replication were examined in the HepG2 2.2.15 cell line and in ducks, and the expressions of signal transducers and transactivator 1 (STAT1), IFN-stimulated gene factor 3 (ISGF3) and 2',5'-oligoadenylate synthetase 1 (OAS1) were investigated by the reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. RESULTS: In vitro,at concentrations from 0.075 to 1.2 nmol/l, rHSA-IFNalpha-2b inhibited the releases of extracellular hepatitis B surface antigen, hepatitis B e antigen and HBV DNA in a dose-dependent manner; rHSA- IFNalpha-2b also increased the levels of STAT1, ISGF3 and OAS1. In vivo, rHSA-IFNalpha-2b reduced the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin and duck hepatitis B virus (DHBV) DNA in the sera of DHBV-infected ducks. CONCLUSIONS: We provide the first evidence that rHSA-IFNalpha-2b significantly inhibits HBV replication in HepG2 2.2.15 cells and in ducks, and that the antiviral effect of rHSA-IFNalpha-2b in vivo is more potent than that of IFNalpha-2b. The anti-HBV mechanism probably operates by triggering the JAK-STAT signaling pathway and increasing the expression of OAS1.
Assuntos
Antivirais/farmacologia , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B do Pato/metabolismo , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/metabolismo , Interferon-alfa/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , 2',5'-Oligoadenilato Sintetase/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases , Bilirrubina/sangue , Linhagem Celular , DNA/sangue , DNA Viral , Avaliação Pré-Clínica de Medicamentos , Patos , Vírus da Hepatite B do Pato/genética , Humanos , Interferon alfa-2 , Fator Gênico 3 Estimulado por Interferon/metabolismo , Fígado/metabolismo , Fígado/patologia , Distribuição Aleatória , Proteínas Recombinantes , Fator de Transcrição STAT1/metabolismo , Albumina Sérica , Albumina Sérica Humana , Regulação para Cima/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
Total ethanol extract and saponins from Chinese herb radix Astragali (huangqi) have been previously shown to possess anti-hepatitis B virus (HBV) activities in vitro. To identify the active ingredients, we isolated a triterpenoid saponin that was determined to be astragaloside IV. In the human HBV-transfected liver cell line HepG(2) 2.2.15, astragaloside IV effectively suppressed secretion of HBV antigens with inhibition rates of 23.6% for the secretion of Hepatitis B surface antigen (HBsAg) and 22.9% for that of Hepatitis B e antigen (HBeAg) at 100 microg/ml after 9 d of treatment. The inhibitory activity of astragaloside IV on secretion of HBV antigens is more potent than that of 3TC without significant cytotoxicity. In duck hepatitis B virus (DHBV)-infected ducklings, astragaloside IV caused 64.0% inhibition at 120 mg/kg, 49.6% inhibition at 40 mg/kg, and 41.7% inhibition at 10 mg/kg to serum DHBVs after 10 d of treatment, and also reduced serum DHBV DNA levels. Together, our results demonstrate that astragaloside IV possesses potent anti-HBV activity.
Assuntos
Astrágalo/química , Medicamentos de Ervas Chinesas/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Carcinoma , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Patos , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B do Pato/genética , Antígenos E da Hepatite B/metabolismo , Humanos , Transfecção/métodosRESUMO
To examine the effect of Gankang Suppository on duck hepatitis B virus (DHBV), the serum biochemistry and hepatic histology in an animal model of DHBV infection, a model of DHBV infection was established by infecting 1-day-old Yingtaogu ducklings with DHBV-positive serum. The successful model was confirmed by PCR assay and 48 ducklings infected with DHBV were randomly divided into 3 groups: a Gankang Suppository treatment group, an acyclovir (ACV) group and a DHBV model group (control), with each group having 16 animals. All the animals were given the medicines for 4 weeks in a row. The serum of the animals was taken 14 and 28 days after the medication and 7 days after drug discontinuation. Real-time PCR was performed to detect the copy numbers of DHBV DNA in the serum. ALT and AST were dynamically monitored. The ducklings were sacrificed on the 7th day after the discontinuation of the treatment and livers were harvested and examined for inflammation and degeneration of liver cells by using HE staining. The results showed that on day 14, 28 after the treatment and day 7 after the withdrawal, the logarithmic values (log) of DHBV DNA copy numbers in ducklings of Gankang Suppository treatment group were significantly lower than that before the treatment (P=0.0092, P=0.0070, P=0.0080, respectively). Compared with DHBV model control group, the ALT level was significantly decreased (P=0.0020, P=0.0019, respectively) on day 28 after the treatment and on day 7 after the withdrawal. The AST level was also reduced on day 14 after the treatment (P=0.0298). Compared with the ACV control group, the level of ALT was lower on day 7 after the withdrawal (P=0.0016). Histologically, the hepatocyte swelling, vacuolous degeneration and acidophilic degeneration in Gankang Suppository treatment group were alleviated 7 days after the withdrawal as compared with model control group (P=0.0282, P=0.0084, P=0.0195, respectively). It is concluded that Gankang Suppository can effectively suppress DHBV replication, reduce the levels of serum ALT and AST and improve hepatic histology.
Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Infecções por Hepadnaviridae/veterinária , Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite Viral Animal/tratamento farmacológico , Aciclovir/administração & dosagem , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Patos , Ácido Glicirrízico/administração & dosagem , Infecções por Hepadnaviridae/sangue , Infecções por Hepadnaviridae/tratamento farmacológico , Hepatite Viral Animal/sangue , Hepatite Viral Animal/patologia , Lentinano/administração & dosagem , Fígado/patologia , Supositórios , Replicação Viral/efeitos dos fármacosRESUMO
The traditional Chinese medicine Oenanthe javanica (OJ) has been used for many years, mainly for the treatment of inflammatory conditions including hepatitis. In this study, human hepatoma Hep G2.2.15 cells culture system and duck hepatitis B virus (DHBV) infection model were used as in vivo and in vitro models to evaluate the anti-HBV effects of total phenolics from Oenanthe javanica (OJTP). The HBeAg and HBsAg concentrations in cell culture medium were determined by using the enzyme immunoassay kit after Hep G2.2.15 cells were treated with OJTP for 9 d. DHBV-DNA in duck serum was analyzed by dot blot hybridization assay. In the cell model, OJTP could dose-dependently inhibit the production of the HBeAg and HBsAg, and the inhibition rates of OJTP on HBeAg and HBsAg in the Hep G2.2.15 cells were 70.12% and 72.61% on day 9, respectively. In the DHBV infection model, OJTP also reduced HBV DNA level in a dose-dependent manner. The DHBV-DNA levels decreased significantly after the treatment with 0.10 g kg(-1)d(-1) and 0.20 g kg(-1)d(-1) OJTP. The inhibition of the peak of viremia was at the maximum at the dose of 0.20 g kg(-1)d(-1) and reached 64.10% on day 5 and 66.48% on day 10, respectively. Histopathological evaluation of the liver revealed significant improvement by OJTP. In conclusion, our results demonstrate that OJTP can efficiently inhibit HBV replication in Hep G2.2.15 cells line in vitro and inhibit DHBV replication in ducks in vivo. OJTP therefore warrants further investigation as a potential therapeutic agent for HBV infections.
Assuntos
Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Oenanthe/química , Fenóis/farmacologia , Animais , Antivirais/isolamento & purificação , Antivirais/farmacologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Patos , Infecções por Hepadnaviridae/tratamento farmacológico , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/efeitos dos fármacos , Antígenos E da Hepatite B/metabolismo , Hepatite Viral Animal/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Fenóis/administração & dosagem , Fenóis/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Fatores de TempoRESUMO
Natural products provide a large reservoir of potentially active agents with anti-hepatitis B virus (HBV) activity. We examined the effect of the polyphenolic extract from Geranium carolinianum L. (PPGC) on HBV replication both in vitro and in vivo. In the human HBV-transfected liver cell line HepG(2) 2.2.15, PPGC effectively suppressed the secretion of the HBV antigens in a dose-dependent manner with IC(50) values of 46.85 microg/ml for HBsAg and 65.60 microg/ml for HBeAg at day 9. Consistent with the HBV antigen reduction, PPGC (100 microg/ml) also reduced HBV DNA level by 35.9%. In the duck hepatitis B virus (DHBV) infected ducks, after PPGC was dosed intragastricly (i.g.) once a day for 10 days, the plasma DHBV DNA level was reduced, with an ED(50) value of 47.54 mg/kg. In addition, Southern blot analysis confirmed the in vivo anti-HBV effect of PPGC in ducks and PPGC also reduced the plasma and the liver DHBV DNA level in a dose-dependent manner. Furthermore, significant improvement of the liver was observed after PPGC treatment, as evaluated by the histopathological analysis.
Assuntos
Antivirais/farmacologia , Geranium/química , Vírus da Hepatite B/efeitos dos fármacos , Extratos Vegetais/farmacologia , Replicação Viral , Animais , Antígenos Virais/biossíntese , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Linhagem Celular , DNA Viral/biossíntese , DNA Viral/sangue , Relação Dose-Resposta a Droga , Patos , Infecções por Hepadnaviridae/tratamento farmacológico , Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite Viral Animal/tratamento farmacológico , Hepatócitos/virologia , Humanos , Concentração Inibidora 50 , Fígado/patologia , Fígado/virologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Carga ViralRESUMO
The Tibetan herb Potentilla anserina L. has been widely used in China for many thousands of years to treat hepatitis-B. Bioassay-guided fractionation of the ethanol extract of the rhizomes led to the isolation of a triterpenoid saponin (TS) that was determined to be 2alpha,3beta,19alpha-trihydroxyurs-12-en-28-oic acid beta-D-glucopyranosyl ester. Using models of HBV infection, this compound was evaluated for its effect on HBV antigene expression in the 2.2.15 cell line in vitro and anti-hepatitis B virus (HBV) activities in Peking ducklings in vivo. Results showed that it could decrease the expression levels of HBsAg, HBeAg and HBVDNA in the 2.2.15 cell culture and the inhibitory effect was not due to the cytotoxity of the triterpenoid saponin. The antiviral study in vivo on Peking ducklings also demonstrated that this compound inhibits duck hepatitis B virus (DHBV) DNA replication.
Assuntos
Infecções por Hepadnaviridae/tratamento farmacológico , Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite Viral Animal/tratamento farmacológico , Fitoterapia , Potentilla/química , Saponinas/farmacologia , Triterpenos/uso terapêutico , Animais , Antivirais/farmacologia , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Replicação do DNA/efeitos dos fármacos , DNA Viral/efeitos dos fármacos , Patos , Anticorpos Anti-Hepatite/sangue , Antígenos de Hepatite/sangue , Humanos , Neoplasias Hepáticas/virologia , Extratos Vegetais/uso terapêutico , Rizoma/química , Saponinas/isolamento & purificação , Saponinas/uso terapêutico , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
OBJECTIVE: To study the viral inhibitory effect of Shenling Yigan Granule (SYG) on duck hepatitis B virus (DHBV) in vivo. METHODS: Chongqing ducks infected with DHBV were used. They were randomly divided into five groups, the small-, medium- and high-dose (1.6 g/kg, 3.2 g/kg, 6.4 g g/kg) SYG groups, the lamivudine positive control group, and the model group. The changes of serum DHBV-DNA, DHB-sAg contents and hepatic pathology were observed. RESULTS: The serum content of DHBV-DNA in the three SYG groups and the positive control group was significantly decreased (P < 0.05), while it was rebounded in the latter at day 7 after stopped lamivudine administration. The change of DHBsAg level was insignificantly in all groups. And the hepatic pathological change in the SYG groups and positive control group was slighter than that in the model control group, but showed insignificant difference in comparison between the SYG groups and the model group (P > 0.05). CONCLUSION: SYG has certain in vivo inhibitory effects on DHBV-DNA.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Infecções por Hepadnaviridae/tratamento farmacológico , Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite Viral Animal/tratamento farmacológico , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Patos , Fitoterapia , Distribuição AleatóriaAssuntos
Medicamentos de Ervas Chinesas/farmacologia , Ácido Glicirrízico/farmacologia , Infecções por Hepadnaviridae , Vírus da Hepatite B do Pato/efeitos dos fármacos , Hepatite Viral Animal , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Patos , Ácido Glicirrízico/uso terapêutico , Infecções por Hepadnaviridae/tratamento farmacológico , Hepatite Viral Animal/tratamento farmacológico , FitoterapiaRESUMO
Anti-DHBV (duck hepatitis B virus) activity was found in the aqueous extracts of Sophora flavescens Ait. in vivo. Liquid chromatography/electrospray ionization ion trap mass spectrometry was applied to characterize the components in duck serum after oral administration of S. flavescens extract. Oxymatrine (1), sophoranol (2), sophoridine (3) and matrine (4) were identified in the serum. Further research on the four compounds was evaluated for their antiviral activity against HBV (hepatitis B virus) in cell culture. The results suggested that oxymatrine, sophoranol and matrine were the efficacy substances for anti-HBV activity in aqueous extracts of S. flavescens Ait.