The Korean herbal formulation Yukmijihwangtang stimulates longitudinal bone growth in animal models

Abstract

Background: Yukmijihwangtang (YJT) is a traditional Korean medicine that has been used to treat kidney-yin deficiency symptoms such as dizziness and tinnitus. In addition, because it is also thought to nourish kidney-yin, it has been used to treat short stature from congenital deficiency. This study evaluated the effects of YJT on longitudinal bone growth in rats. Methods: Female adolescent rats were randomly assigned to groups that received distilled water (per os [p.o.] twice a day; control), recombinant human growth hormone (rhGH; 20 μg/kg, subcutaneous [s.c.] once a day), or two different doses of YJT (100 or 300 mg/kg, p.o. twice a day). In each group, treatment was maintained for 4 days. Rats were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU; 50 mg/kg) to label proliferating chondrocytes on days 2 - 4. Tetracycline hydrochloride (20 mg/kg) was injected intraperitoneally to form fluorescent bands on the growth plates on day 3 for measuring the longitudinal bone growth rate. Expression of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate was identified using immunohistochemistry. Results: There was a significant increase in the rate of bone growth in the 300 mg/kg YJT group (523.8±23.7 μm/day; P<0.05) compared to the control group (498.0±23.8 μm/day), while the 100 mg/kg YJT group exhibited a non-significant increase. The number of BrdU-positive cells in the chondrocytes of the rhGH-treated group exhibited a significant increase (103.8±34.2 cells/mm2) compared to that of the control group (70.3±19.7 cells/mm2), while the 300 mg/kg YJT group had a non-significant increase. Additionally, IGF-1 and BMP-2 were highly expressed in the growth plate in the 300 mg/kg YJT and rhGH groups. Conclusions: YJT increased the longitudinal bone growth rate by stimulating chondrocyte proliferation with increasing increments of local IGF-1 and BMP-2 expression. Based on these findings, YJT may be a therapeutic candidate for the treatment of growth retardation during adolescence.