Abstract
Eleutherococcus extract mixture (EEM) is an herbal mixture of dried stem of Eleutherococcus sessiliflorus and germinated barley, which has been highly effective, in previous screening and among the traditional medicines to tonify innate qi and acquired qi, respectively. In this study, we investigate the effects of EEM on endochondral bone formation. Female adolescent rats were given EEM, growth hormone or vehicle for 10 days. Tetracycline was intraperitoneally injected to light the fluorescent band 72 h before sacrifice to determine endochondral bone formation. In order to evaluate endocrine or paracrine/autocrine mechanisms, expressions of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), or bone morphogenetic protein 2 (BMP2) were evaluated after EEM administration in liver or growth plate (GP). EEM oral administration significantly increased endochondral bone formation and proliferative and hypertrophic zonal heights of tibial GP. EEM also upregulated hepatic IGF1 and IGFBP3 mRNA expressions, and IGF1 and BMP2 expressions in GP. Taken together, EEM increases endochondral bone formation through stimulating proliferation and hypertrophy with upregulation of hepatic IGF1 and IGFBP3 expressions. Considering immunohistochemical studies, the effect of EEM may be due to increased local IGF1 and BMP2 expression in GP, which may be considered growth hormone (GH)-dependent endocrine and autocrine/paracrine pathways.
Highlights
Short stature is defined as the height of individuals who are shorter than two standard deviations compared with the mean height of age, gender, and population [1]
In order to evaluate the possible endocrine or paracrine/autocrine mechanism by which Eleutherococcus extract mixture (EEM) can exert its growth-stimulating effect, we assessed insulin-like growth factor-1 (IGF1) and bone morphogenetic protein 2 (BMP2) expressions in growth plate (GP), and the insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) mRNA expressions in liver
The result suggests that EEM increases endochondral bone formation, which is important for the height growth process
Summary
Short stature is defined as the height of individuals who are shorter than two standard deviations compared with the mean height of age, gender, and population [1]. In the case of ISS, the height increase in children treated with 4–7 years of long-term GH was just 3.5–7.5 cm and the estimated cost of GH treatment for adult height increase is approximately 9000–60,000 dollars/cm [12,13] Another concern regarding GH therapy is that it could have adverse psychosocial consequences due to the treatment burden resulting from daily subcutaneous injections [14]. 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. In order to evaluate the possible endocrine or paracrine/autocrine mechanism by which EEM can exert its growth-stimulating effect, we assessed insulin-like growth factor-1 (IGF1) and bone morphogenetic protein 2 (BMP2) expressions in GP, and the IGF1 and insulin-like growth factor binding protein 3 (IGFBP3) mRNA expressions in liver
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