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

Abstract

BackgroundYukmijihwangtang (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.MethodsFemale 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.ResultsThere 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.ConclusionsYJT 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.

Effects of recombinant human growth hormone on protein malnutrition and IGF-1 and IL-2 gene expression levels in chronic nephrotic syndrome

“…Nephrotic syndrome is the most clinically common kidney-related disease at present, posing a serious threat to physical health ( 1 ). In its pathogenesis, immune dysfunction is the main pathogenic and initiative factors ( 2 ). At the same time, patients are often accompanied with malnutrition due to the loss of a large number of plasma proteins ( 3 ).…”

Effects of Eleutherococcus Extract Mixture on Endochondral Bone Formation in Rats

“…Unlike animal models for disease research, this model has had to continually improve its design because it has to identify the effects in normal rats. Unlike previous studies which did not perform dose-dependent studies [ 16 ] or measure the expression of growth factors in the liver [ 15 , 17 ], in this study EEM showed a significant effect on these parameters. EEM is the promising candidate of our group derived from data using more than 50 rats per group to confirm the effects on endochondral bone formation, while previous studies confirmed the effects using 8 to 14 rats per group [ 15 , 16 , 17 ].…”

“…[ 69 , 70 ]. To improve accuracy, the effects of EEM on endochondral bone formation was measured for 72 h after a 10-day administration, unlike previous experiments in which the effects were measured for 48 h after a four day administration [ 15 , 16 , 17 ]. In addition, sagittal cutting was used instead of coronal cutting to reduce variations of bone sections.…”

“…Therefore, we selected medicinal herbs from the Dongeuibogam that have been used to tonify innate qi or acquired qi . We screened traditional medicinal herbs to discover the safe oral growth stimulant using an established animal model which could assess the endochondral bone formation using tetracycline in rats [ 15 , 16 , 17 ]. Eleutherococcus extract mixture (EEM) is an herbal mixture of dried stem of Eleutherococcus sessiliflorus and germinated barley, which was has been highly effective in previous screening, and among the traditional medicines to tonify innate qi and acquired qi, respectively.…”

A Mixture of Humulus japonicus Increases Longitudinal Bone Growth Rate in Sprague Dawley Rats

“…Overall, this therapy is advantageous; however, it should only be prescribed for long-term use in children or adults who need supplementation with growth hormone, and there can be several side effects when using it in healthy patients [10,11]. Therefore, recent studies have attempted to determine new alternative therapies using herbal remedies that have effects on longitudinal bone growth [12][13][14][15]. Thus, we investigated the effects of an herbal mixture of Humulus japonicus on longitudinal bone growth in normal Sprague Dawley (SD) rats.…”