Herbal formulation, Yukmi-jihang-tang-Jahage, regulates bone resorption by inhibition of phosphorylation mediated by tyrosine kinase Src and cyclooxygenase expression

• Published in: Journal of ethnopharmacology Vol. 106; no. 3; pp. 333 - 343
• Main Authors: Jin, Un-Ho, Kim, Dong-Il, Lee, Tae-Kyun, Lee, Dong-Nyung, Kim, June-Ki, Lee, In-Seon, Kim, Cheorl-Ho
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 19.07.2006; Elsevier
• Subjects: Alisma plantago-aquatica; Alisma plantago-aquatica var. orientale; Animals; bioassays; Biological and medical sciences; biosynthesis; Bone resorption; Bone Resorption - metabolism; chemical constituents of plants; Cornus officinalis; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; Cyclooxygenase Inhibitors - therapeutic use; Cytokines - pharmacology; Dioscorea; Dioscorea japonica; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; enzyme activity; enzyme inhibitors; ethnobotany; Female; General pharmacology; herbal medicines; Hominis placenta; IL-1β; IL-6; Medical sciences; medicinal plants; medicinal properties; Mice; Mice, Inbred BALB C; Osteoblast; osteoblasts; Osteoblasts - drug effects; Osteoporosis; Osteoporosis - chemically induced; Osteoporosis - drug therapy; Ovariectomy; Paeonia suffruticosa; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; phosphorylation; Phytotherapy; plant extracts; Plants, Medicinal; Prostaglandin E2; prostaglandin synthase; Prostaglandin-Endoperoxide Synthases - metabolism; prostaglandins; Protein tyrosine kinase inhibitor; protein-tyrosine kinases; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Rats; Rehmannia glutinosa; Smilax; Smilax glabra; TGF-β; TNF-α; traditional medicine; Yukmi-jihang-tang-Jahage; South Korea; Bone resorption; Osteoporosis; TNF-α; Yukmi-jihang-tang-Jahage; Prostaglandin E2; Osteoblast; Protein tyrosine kinase inhibitor; TGF-β; IL-1β; IL-6; Prostaglandin-endoperoxide synthase; Phosphorylation; Transforming growth factor β; Diseases of the osteoarticular system; Medicinal plant; Osteoarticular system; Interleukin 6; Eicosanoid; Formulation; Protein-tyrosine kinase; Tumor necrosis factor α; Enzyme; Pharmacognosy; Tyrosine kinase inhibitor; Arachidonic acid derivatives; Transferases; Cytokine; Enzyme inhibitor; Interleukin 1β; Plant origin; Bone; Oxidoreductases
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2006.01.012

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-1β (IL-1β), tumor necrosis factor-α (TNF-α) and/or interleukin-6 (IL-6). IL-1β and IL-6 and to a lesser extent TNF-α, enhanced COX-2 mRNA levels in calvarial osteoblasts. TGF-β, YJ (100 μg/ml) and their combinations of YJ + TGF-β reduced the COX-2 mRNA level, PGE2 biosynthesis and bone resorption induced by IL-1β, TNF-α, 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 16 μg/ml. YJ dose-dependently reduced the hypercalcemia induced in mice by IL-1β 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-β, TNF-α, 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.