Among the mammalian
matrix metalloproteinases (
MMPs), MMP-1, -3 and -13 are
collagenases. Particularly, MMP-13 is important for the degradation of major
collagens in cartilage under certain pathological conditions such as
osteoarthritis. To establish a potential therapeutic strategy for cartilage degradation disorders, the effects of 11 ginseng
saponins (
ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rg5, Rk1 and F4) on MMP-13 induction were examined in a human chondrocyte cell line, SW1353. Among these, several
saponins including
ginsenoside Rc, Rd, Rf, Rg3 and F4 were found to inhibit MMP-13 expression in IL-1β-treated SW1353 cells at non-cytotoxic concentrations (1-50 μM). The most prominent inhibitors were
ginsenosides F4 and Rg3.
Ginsenoside F4 inhibited MMP-13 expression 33.5% (P<0.05), 57.9% (P<0.01) and 90.0% (P<0.01)
at 10, 30 and 50 μM, respectively. Significantly,
ginsenoside F4 was found to strongly inhibit activation of
p38 mitogen-activated protein kinase in signal transduction pathways (86.6 and 100.0% inhibition at 30 and 50 μM, P<0.01). The MMP-13 inhibitory effect was also supported by the finding that
ginsenosides F4 and Rg3 reduced
glycosaminoglycan release from IL-1α-treated rabbit joint cartilage culture to some degree. Taken together, these results indicate that several
ginsenosides inhibit MMP-13 expression in IL-1β-treated chondrocytes.
Ginsenoside F4 and Rg3 blocked cartilage breakdown in rabbit cartilage tissue culture. Thus, it is suggested that certain
ginsenosides have therapeutic potential for preventing
cartilage collagen matrix breakdown in diseased tissues such as those found in patients with arthritic disorders.