Anti-
bone resorption properties of the Korean herbal medicine,
Yukmi-jihang-tang (YJ), which is comprised of seven herbs such as Rehmannia glutinosa Libosch, Dioscorea japonica THUNB, Cornus officinalis SIEB et. ZUCC, Smilax glabra ROXB, Paeonia suffruticosa ANDR, Alisma platago-aquatica var. orientale SAMUELS and Hominis placenta, were investigated.
Cyclooxygenase-2 (COX-2) and
tyrosine kinase involve on
prostaglandin E2 (
PGE2) production in mouse calvarial osteoblasts stimulated by
cytokine interleukin-1beta (IL-1beta),
tumor necrosis factor-alpha (
TNF-alpha) and/or
interleukin-6 (IL-6). IL-1beta and
IL-6 and to a lesser extent
TNF-alpha, enhanced COX-2
mRNA levels in calvarial osteoblasts.
TGF-beta, YJ (100microg/ml) and their combinations of YJ+TGF-beta reduced the COX-2
mRNA level,
PGE2 biosynthesis and
bone resorption induced by IL-1beta,
TNF-alpha,
IL-6 or their combination. Finally, YJ inhibits in vitro and in vivo
bone resorption by inhibition of phosphorylation of
peptide substrates. The
parathyroid hormone-induced
bone resorption in mouse fetal long bone cultures was inhibited with an IC(50) of 16microg/ml. YJ dose-dependently reduced the
hypercalcemia induced in mice by IL-1beta and partly prevented bone loss and microarchitectural changes in young ovariectomized rats, showing that the protective effect on bone was exerted via the inhibition of
bone resorption. These results indicate that the synergy between IL-beta,
TNF-alpha,
IL-6 on
PGE2 production is due to an enhanced gene expression of COX-2 and that
tyrosine kinase(s) are involved in the signal transduction of COX-2 in mouse calvarial osteoblasts. Thus, YJ as a possible
Src family kinase inhibitor may be useful for the treatment of diseases associated with elevated bone loss. This result also suggested that the YJ extracts is effective for bone resorptive action in bone cells.