2011 Volume 28 Issue 3 Pages 139-148
Glycyrrhizin (a major component of licorice root) affects the entry of a virus into cells mostly by suppressing the fluidity of the plasma membrane and viral envelope. This activity has been recognized in cells infected by human immunodeficiency virus (HIV) and other viruses. In these infections, apoptosis is initiated via virus-cell membrane interactions. Therefore, the anti-apoptotic activity of glycyrrhizin and its possible mechanism was investigated in the current study. Anti-apoptotic activity of glycyrrhizin was recognized at 0.15mM by DNA and nuclear fragmentation assays. Glycyrrhizin decreased the number of apoptotic cells with no effect on HIV production at this concentration (0.15mM) in cultures of MT4 cells infected with HIV, although 3'-azido-2',3'-dideoxythymidine (AZT) suppressed both the proportion of apoptotic cells and HIV production to the similar levels in a dose-dependent manner. Glycyrrhizin inhibited apoptosis induced by feline immunodeficiency virus (FIV) at 0.6mM with no effect on FIV production as assessed by FIV-reverse transcriptase activity in cultures of Mya-1 cells infected with FIV. Apoptosis was prevented by pre-treatment with glycyrrhizin (P<0.05), but not AZT. Glycyrrhizin diminished the expression of CD4 in untreated cells to 54% dose-dependently without affecting the expression of Fas, CXCR4, and MHC class I. In conclusion, glycyrrhizin diminished the expression of cell surface CD4, which might affect the cross-linking of CD4 with HIV, thereby inhibiting the cascade leading to apoptosis. Because the binding of FIV-spike with CD4 was not recognized, the inhibitory activity of glycyrrhizin against FIV-induced apoptosis may be caused through the cascade involving other cell-surface molecule (s).
