ABSTRACT
Rheum palmatum, Chinese traditional herb, exhibits a great variety of anti-cancer and anti-viruses properties. This study rates antiviral activity of R. palmatum extracts and its components against Japanese encephalitis virus (JEV) in vitro. Methanol extract of R. palmatum contained higher levels of aloe emodin, chrysophanol, rhein, emodin and physcion than water extract. Methanol extract (IC50 = 15.04 µg/ml) exhibited more potent inhibitory effects on JEV plaque reduction than water extract (IC50 = 51.41 µg/ml). Meanwhile, IC50 values determined by plaque reduction assay were 15.82 µg/ml for chrysophanol and 17.39 µg/ml for aloe-emodin, respectively. Virucidal activity of agents correlated with anti-JEV activity, while virucidal IC50 values were 7.58 µg/ml for methanol extract, 17.36 µg/ml for water extract, 0.75 µg/ml for chrysophanol and 0.46 µg/ml for aloe-emodin, respectively. In addition, 10 µg/ml of extract, chrysophanol or aloe emodin caused 90 % inhibition of JEV yields in cells and significantly activated gamma activated sequence-driven promoters. Hence, methanol extract of R. palmatum and chrysophanol with high therapeutic index might be useful for development of antiviral agents against JEV.
Subject(s)
Anthraquinones/pharmacology , Antiviral Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Encephalitis Virus, Japanese/drug effects , Rheum/chemistry , Virus Replication/drug effects , Animals , Antiviral Agents/isolation & purification , Cell Line , Cell Survival/drug effects , Drugs, Chinese Herbal/isolation & purification , Encephalitis Virus, Japanese/growth & development , Encephalitis Virus, Japanese/physiology , Ethnopharmacology , Genes, Reporter/drug effects , Inhibitory Concentration 50 , Interferon-Stimulated Gene Factor 3/agonists , Interferon-Stimulated Gene Factor 3/genetics , Interferon-Stimulated Gene Factor 3/metabolism , Luciferases, Firefly/chemistry , Luciferases, Firefly/genetics , Luciferases, Firefly/metabolism , Mesocricetus , Methanol/chemistry , Promoter Regions, Genetic/drug effects , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Solvents/chemistryABSTRACT
Isatis indigotica is widely used in Chinese Traditional Medicine for clinical treatment of virus infection, tumor, and inflammation, yet its antiviral activities remain unclear. This study probed antiviral activity of I. indigotica extract and its marker compounds against Japanese encephalitis virus (JEV). I. indigotica methanol extract, indigo, and indirubin proved less cytotoxic than other components, showing inhibitory effect (concentration-dependent) on JEV replication in vitro. Time-of-addition experiments proved the extract, indigo, and indirubin with potent antiviral effect by pretreatment (before infection) or simultaneous treatment (during infection), but not posttreatment (after entry). Antiviral action of these agents showed correlation with blocking virus attachment and exhibited potent virucidal activity. In particular, indirubin had strong protective ability in a mouse model with lethal JEV challenge. The study could yield anti-JEV agents.
