Identification of natural compounds with anti-hepatitis B virus activity from Rheum palmatum L. ethanol extract.
BACKGROUND
Hepatitis B virus (HBV) infection is a severe health problem in the world; however, there is still no satisfactory therapeutic strategy for the HBV infection. In search for new anti-HBV agents with higher efficiency and less side effects, the anti-HBV activities of traditional Chinese medicine Rheum palmatum L. ethanol extract (RPE) and isolated anthraquinones were evaluated.


METHODS
The anti-HBV activities of RPE and isolated anthraquinones were demonstrated in a stable HBV-producing cell line HepG2 2.2.15 by using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and Southern blot analysis.


RESULTS
RPE could inhibit HBV-DNA production and HBsAg expression in a dose-dependent manner. The concentration of 50% HBV-DNA inhibition (IC(50)) of RPE was calculated at 212.36 +/- 11 microg/ml. Six anthraquinones were isolated from RPE by using RP-HPLC. Five free anthraquinones showed weakly or slightly inhibitory activities against HBV. The only combined anthraquinone chrysophanol 8-O-beta-D-glucoside exhibited significant activity against HBV DNA production and antigens expression with an IC(50) value of 36.98 +/- 2.28 microg/ml on HBV DNA inhibition. Endogenous HBV DNA polymerase activity assay indicated that chrysophanol 8-O-beta-D-glucoside might be a potential inhibitor of the HBV DNA polymerase.


CONCLUSIONS
The results suggested that RPE could effectively inhibit HBV. The combined anthraquinone chrysophanol 8-O-beta-D-glucoside is the major active compound in RPE and could be a promising candidate for the development of new anti-HBV drugs in the treatment of HBV infection.
Li
Zhi
Z
College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, People's Republic of China. lizhi@snnu.edu.cn <lizhi@snnu.edu.cn>
Li
Li-Jun
LJ
Sun
Yan
Y
Li
Jing
J
D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000431:Ethanol; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015394:Molecular Structure; D019384:Nucleic Acid Synthesis Inhibitors; D010936:Plant Extracts / Q000737:chemistry*; D012250:Rheum / Q000737:chemistry*