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. 2017 May 2;17(1):239.
doi: 10.1186/s12906-017-1651-1.

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

Sung-Min Cho  1   2 , Sun Haeng Lee  3 , Donghun Lee  4 , Ji Hong Lee  1 , Gyu Tae Chang  1   5 , Hocheol Kim  6 , Jin Yong Lee  7   8
Affiliations

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

Sung-Min Cho et al. BMC Complement Altern Med. .

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.

Keywords: Growth plate; Longitudinal bone growth; Recombinant human growth hormone; Yukmijihwangtang.

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Figures

Fig. 1
Fig. 1
Three-dimensional high-performance chromatography of Yukmijihwangtang (YJT)
Fig. 2
Fig. 2
Fluorescent photomicrographs of longitudinal sections of the proximal tibia in the growth plate. a Control group (distilled water), b recombinant human growth hormone (rhGH) group (20 μg/kg), c 100 mg/kg YJT group, and d 300 mg/kg YJT group. The fluorescent line corresponds to the injection of tetracycline, which binds with calcium and can be detected with ultraviolet illumination. The arrow between the fluorescent line formed by the tetracycline and the epiphyseal end line of the growth plate indicates the extent of bone growth during the 48 h study period. Scale bar = 200 μm
Fig. 3
Fig. 3
Effects of YJT on longitudinal bone growth rate in adolescent rats. The control group: received distilled water and the rhGH group received 20 μg/kg rhGH. Values are means ± SD of eight rats. *P < 0.05 compared to the control group
Fig. 4
Fig. 4
Representative images of 5-bromo-2’-deoxyuridine (BrdU)-labeled chondrocytes in the growth plates in the proximal tibia. The control group received distilled water, the rhGH group received 20 μg/kg rhGH and the YJT group received 300 mg/kg YJT. Green: BrdU-labeled chondrocyte. Scale bar = 100 μm
Fig. 5
Fig. 5
Effects of YJT on chondrocyte proliferation in the growth plates of adolescent female rats. BrdU-positive cells were quantified. The control group received distilled water, the rhGH group received 20 μg/kg rhGH and the YJT group received 300 mg/kg YJT. Values are means ± SD of eight rats. *P < 0.05 compared with the control group
Fig. 6
Fig. 6
Immunohistochemical localization of bone morphogenetic protein (BMP)-2 and insulin-like growth factor (IGF)-1 in the growth plate. The control group received distilled water, the rhGH group received 20 μg/kg rhGH and the YJT group received 300 mg/kg YJT. RZ, resting zone; PZ, proliferative zone; HZ, hypertrophic zone. Scale bar = 400 μm
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