Osthole increases glycosylation of hepatitis B surface antigen and suppresses the secretion of hepatitis B virus in vitro.
During screening of Chinese herbal medicines for the activities against hepatitis B virus (HBV), a known pure compound, osthole, was found to inhibit the secretion of HBV surface antigens in vitro. The secretion of hepatitis B surface antigen (HBsAg) in culture medium of MS-G2 and HuH-7 cells transfected with HBV DNA decreased by 60% to 70% after osthole treatment, without any detectable cytotoxic effects. Both 42-nm Dane particles and 22-nm subviral HBsAg particles were significantly reduced as revealed by density gradient analysis of viral particles and the endogenous; HBV DNA polymerase assay. The production of naked HBcAg particles was not changed by osthole treatment. The steady-state level of HBV-specific messenger RNA (mRNA) was not altered by osthole treatment, as revealed by Northern blot analysis, Immunoprecipitation of culture medium showed that the ratio of glycosylated versus nonglycosylated HBsAg increased after osthole treatment. Kinetic studies revealed that osthole increased the glycosylation rate of HBsAg, thus altering the ratio of glycosylated to unglycosylated HBsAg. The increase of glycosylation of HBsAg by osthole was blocked by tunicamycin, an inhibitor of protein glycosylation. We conclude that osthole suppresses the secretion of HBV in cell culture probably because of its novel function in increasing the glycosylation of HBsAg.
Huang
R L
RL
Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan 11221, Republic of China.
Chen
C C
CC
Huang
Y L
YL
Hsieh
D J
DJ
Hu
C P
CP
Chen
C F
CF
Chang
C
C
D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology*; D006031:Glycosylation / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D014771:Virion / Q000187:drug effects / Q000378:metabolism
D000998:Antiviral Agents; D003374:Coumarins; D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D014415:Tunicamycin; C046627:osthol