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1.
Zhongguo Zhong Yao Za Zhi ; 40(15): 3047-52, 2015 Aug.
Article in Chinese | MEDLINE | ID: mdl-26677709

ABSTRACT

To verify the effect of echinacoside on replication and antigen expression of hepatitis B virus (HBV) by using HBV-transfected HepG2. 2. 15 cells as the in vitro model. The ELISA method was used to determine HBeAg and HBsAg levels in cellular supernatants. The effect of echinacoside on HBV replication was studied by using HBV transgenic mice as the in vivo model. First of all, the HBV DNA level in hepatic tissues was quantified with PCR method. Meanwhile, the serum transaminase levels and hepatic pathological changes were also evaluated. Subsequently, HBV transgenic mice were divided into five groups: the control group, the lamivudine group (50 mg · kg(-1)) and echinacoside high, medium and low dose group (50, 25 and 12.5 mg · kg(-1)). The mice were orally administered with drugs once per day for 30 days. At the 31st day, the mice serum was separated to measure HBsAg, HBeAg and HBV DNA. Additionally, the liver HBV DNA level and histopathological change were detected. The results indicated that echinacoside at 50 and 100 mg · L(-1) suppressed significantly HBsAg and HBeAg expressions on the sixth day, with the maximum inhibition ratios of 42.68% and 46.29%; And echinacoside at 100 mg · L(-1) also showed an inhibitory effect on HBV DNA. Besides, echinacoside at 50 mg · kg(-1) inhibited significantly HBsAg and HBeAg expressions of HBV transgenic mice, with the inhibition ratios of 42.82% and 29.12%, and reduced markedly the serum HBV DNA level in HBV transgenic mice. In conclusion, the study suggested that echinacoside has a strong effect against HBV replication and antigen expression.


Subject(s)
Glycosides/pharmacology , Hepatitis B virus/drug effects , Virus Replication/drug effects , Animals , DNA, Viral/blood , Female , Hep G2 Cells , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/physiology , Humans , Male , Mice , Mice, Inbred C57BL
2.
Mol Med Rep ; 11(6): 4706-12, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25633656

ABSTRACT

Heme oxygenase­1 (HO­1) possesses significant potential as a drug target for hepatitis B, which may be transferable to patient therapy. The aim of the present study was to clarify the dynamic correlation between the hepatitis B virus (HBV) and HO­1. The levels of HBV replication and expression of HO­1 were investigated in HepG2.2.15 hepatoma cells following exposure to 5­50 µM hemin for 1­6 days. The mRNA expression levels of HO­1 were then detected using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). HBV replication levels were determined by enzyme­immunoassay and a PCR­fluorescence quantitation assay. The results of the present study demonstrated that the mRNA expression levels of HO­1 increased in a dose­dependent manner in the HepG2.2.15 cells, following exposure to 5­50 µM hemin. The mRNA expression levels of HO­1 reached a peak following exposure of the cells to hemin for three days, subsequently the expression of HO­1 decreased. Following exposure to hemin at an optimal concentration of 50 µM for 1­6 days, the levels of the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the cells were significantly reduced. This marked reduction in the expression of HBsAg and HBeAg reached its peak on the first day, following which the inhibition weakened as the duration of exposure increased. In addition, the inhibition of HBV DNA replication increased with the a longer duration of exposure. Furthermore, HBV DNA levels were significantly decreased following exposure to hemin for 3­6 days. In conclusion, the present study demonstrated that induced expression of HO­1 interfered with HBV replication in a dose and time­dependent manner, implying that a reduction of the HBV viral load may contribute to upregulation in the expression of HO­1.


Subject(s)
Heme Oxygenase-1/metabolism , Hepatitis B virus/physiology , DNA, Viral/metabolism , Down-Regulation/drug effects , Heme Oxygenase-1/genetics , Hemin/toxicity , Hep G2 Cells , Hepatitis B Surface Antigens/metabolism , Hepatitis B e Antigens/metabolism , Humans , RNA, Messenger/metabolism , Transcription, Genetic/drug effects , Virus Replication/drug effects
3.
Biol Pharm Bull ; 37(7): 1214-20, 2014.
Article in English | MEDLINE | ID: mdl-24759764

ABSTRACT

Hepatitis B is the most common serious liver infection in the world. To date, there is still no complete cure for chronic hepatitis B. Natural caffeic acid analogues possess prominent antiviral activity, especially anti-hepatitis B virus (HBV) and anti-human immunodeficiency virus effects. Cichoric acid is a caffeic acid derivative from Cichorium intybus. In the study, the anti-hepatitis B property of cichoric acid was evaluated by the D-galactosamine (D-GalN)-induced normal human HL-7702 hepatocyte injury model, the duck hepatitis B virus (DHBV)-infected duck fetal hepatocytes and the HBV-transfected cell line HepG2.2.15 cells, respectively. The results showed that cichoric acid attenuated significantly D-GalN-induced HL-7702 hepatocyte injury at 10-100 µg/mL and produced a maximum protection rate of 56.26%. Moreover, cichoric acid at 1-100 µg/mL inhibited markedly DHBV DNA replication in infected duck fetal hepatocytes. Also, cichoric acid at 10-100 µg/mL reduced significantly the hepatitis B surface and envelope antigen levels in HepG2.2.15 cells and produced the maximum inhibition rates of 79.94% and 76.41%, respectively. Meanwhile, test compound at 50-100 µg/mL inhibited markedly HBV DNA replication. In conclusion, this study verifies the anti-hepatitis B effect of cichoric acid from Cichorium intybus leaves. In addition, cichoric acid could be used to design the antiviral agents.


Subject(s)
Caffeic Acids/pharmacokinetics , Cichorium intybus/chemistry , Hepatitis B Virus, Duck/drug effects , Hepatocytes/drug effects , Protective Agents/pharmacology , Succinates/pharmacokinetics , Animals , Caffeic Acids/isolation & purification , Cell Survival/drug effects , Cytoprotection/drug effects , DNA, Viral/drug effects , Dose-Response Relationship, Drug , Ducks , Galactosamine/pharmacology , Hep G2 Cells , Hepatitis B Surface Antigens/metabolism , Hepatitis B Virus, Duck/genetics , Hepatitis B Virus, Duck/growth & development , Hepatocytes/virology , Humans , Molecular Structure , Plant Leaves/chemistry , Protective Agents/isolation & purification , Succinates/isolation & purification , Virus Replication/drug effects
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