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1.
Artigo em Inglês | MEDLINE | ID: mdl-22701506

RESUMO

The anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid isolated from Laggera alata was studied using the D-galactosamine- (D-GalN-) induced hepatocyte damage model, HepG2.2.15 cells, and with HBV transgenic mice. In vitro results showed that 3,4-O-dicaffeoylquinic acid improved HL-7702 hepatocyte viability and markedly inhibited the production of HBsAg and HBeAg. At a concentration of 100 µg/mL, its inhibitory rates on the expression levels of HBsAg and HBeAg were 89.96% and 81.01%, respectively. The content of hepatitis B virus covalently closed circular DNA (HBV cccDNA) in HepG2.2.15 cells was significantly decreased after the cells were treated with the test compound. In addition, 3,4-O-dicaffeoylquinic acid significantly increased the expression of heme oxygenase-1 (HO-1) in HepG2.2.15 cells. In vivo results indicated that the test compound at concentrations of 100 µg/mL significantly inhibited HBsAg production and increased HO-1 expression in HBV transgenic mice. In conclusion, this study verifies the anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid. The upregulation of HO-1 may contribute to the anti-HBV effect of this compound by reducing the stability of the HBV core protein, which blocks the refill of nuclear HBV cccDNA. Furthermore, the hepatoprotective effect of this compound may be mediated through its antioxidative/anti-inflammatory properties and by the induction of HO-1 expression.

2.
Sci Pharm ; 80(2): 447-56, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22896829

RESUMO

Laggera alata extract (LAE) was quantitatively analyzed, and its principle components isochlorogenic acids were isolated and authenticated. Protective properties of LAE were studied using a d-galactosamine (d-GalN)-induced injury model in neonatal rat hepatocytes and a d-GalN-induced acute liver damage model in mice. Meanwhile, the effect of isochlorogenic acids derived from LAE on d-GalN-induced hepatocyte injury were also measured in vitro. LAE at concentrations of 10-100 µg/ml significantly reduced cellular leakage of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and improved cell viability. The isochlorogenic acids (4,5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid and 3,4-O-dicaffeoylquinic acid) at concentrations of 1-100 µg/ml also remarkably improved viability of hepatocytes. The oral treatment of LAE at doses of 50, 100 and 200 mg/kg markedly reduced the serum AST and ALT activity of mice and resulted in significant recovery of hepatocytes in liver sections.

3.
J Ethnopharmacol ; 144(1): 190-4, 2012 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-22982394

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The aim of this study was to determine the anti-hepatitis B effect of isochlorogenic acid A isolated from Laggera alata (Asteraceae), a traditional Chinese herbal medicine. MATERIALS AND METHODS: The anti-hepatitis B activity of isochlorogenic acid A was evaluated by the D-galactosamine (D-GalN)-induced HL-7702 hepatocyte damage model and the HBV-transfected HepG2.2.15 cells. RESULTS: Isochlorogenic acid A significantly improved HL-7702 hepatocyte viability and markedly inhibited the productions of HBsAg and HBeAg. The inhibitory rates of isochlorogenic acid A on the HBsAg and HBeAg expressions were 86.9% and 72.9%, respectively. In addition, isochlorogenic acid A declined markedly the content of hepatitis B virus covalently closed circular DNA (HBV cccDNA) and induced significantly the heme oxygenase-1 (HO-1) expression in HepG2.2.15 cells. CONCLUSIONS: Isochlorogenic acid A was verified to possess the potent anti-hepatitis B activity. The anti-HBV target of isochlorogenic acid A is probably associated with blocking the translation step of the HBV replication. Overexpression of HO-1 may contribute to the anti-HBV activity of isochlorogenic acid A by reducing the stability of the HBV core protein and thus blocking the refill of nuclear HBV cccDNA. Additionally, the hepatoprotective effect of isochlorogenic acid A could be achieved by its antioxidative property and induction of HO-1.


Assuntos
Antivirais/farmacologia , Asteraceae , Ácido Clorogênico/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Antígenos Virais/análise , Sobrevivência Celular/efeitos dos fármacos , Ácido Clorogênico/farmacologia , DNA Viral/análise , Heme Oxigenase-1/metabolismo , Células Hep G2 , Hepatite B/prevenção & controle , Vírus da Hepatite B/genética , Humanos
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