Skeletal Growth and IGF Levels in Rats after HT042 Treatment

Abstract

HT042, a new herbal prescription consisting of Astragalus membranaceus, Phlomis umbrosa and Eleutherococcus senticosus, is used in traditional Korean medicine to stimulate growth in children. This study was conducted to investigate the effects of HT042 on skeletal growth, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels, and oestrogenic activity in female rats. Female Sprague-Dawley rats were divided into control, recombinant human growth hormone (rhGH; 20 µg/kg/day), and HT042 (100 mg/kg/day) groups and treated for 3 weeks. Axial skeletal growth, femur length, and growth plate length were measured every 3 weeks. The serum IGF-1 and IGFBP-3 levels were analysed. Moreover, the oestrogenic activity of the herbal extracts in the immature and ovariectomized rats was tested. The nose-anus, nose-tail, femur and growth-plate lengths were increased significantly in the HT042 group. Both IGF-1 and IGFBP-3 were highly expressed in the hypertrophic zone of the growth plate. The serum IGF-1 levels were increased. Moreover, HT042 had no uterotrophic effects in the rats. Consequently, HT042 promoted longitudinal bone growth by stimulating cell proliferation in the epiphyseal plate and inducing the expression of IGF-1 without an oestrogenic response. HT042 may be helpful in stimulating growth in children with short stature.

Astragalus Extract Mixture HT042 Improves Bone Growth, Mass, and Microarchitecture in Prepubertal Female Rats: A Microcomputed Tomographic Study

“…The tibial growth rate in the control group was 372.2 and 228.0  μ m/day during the first and second weeks, respectively, which corresponded with the previous observation [18, 19]. HT042 was shown to increase the tibial growth rate, which confirmed our previous studies on linear bone growth [13, 14]. It was noteworthy that the growth rate reached levels that were comparable to those induced by GH.…”

“…The hypertrophic chondrocytes mineralize the cartilage matrix by secreting matrix vesicles and then osteoblasts deposit bone matrix on the remaining cartilage, resulting in trabecular bone formation [21]. During the process of longitudinal bone growth, HT042 stimulates the proliferation and hypertrophy of chondrocytes, which result in increased growth plate height [13, 14]. The mechanism underlying HT042-induced linear growth involves the stimulation of GH secretion and subsequent production of systemic and local IGF-1 [13–15].…”

“…The length of the tibia was measured at baseline and then weekly for 2 weeks using in vivo μ -CT. In comparison with our previous study using densitometry [14], we achieved more accurate three-dimensional (3D) analysis of bone length in a nondestructive way. Volumetric BMD and microarchitectural changes in the trabecular and cortical bone of the tibia were measured after 2 weeks using ex vivo μ -CT.…”

“…HT042 was found to increase height growth rate in children with mild short stature in a 12-week placebo-controlled trial, which was confirmed by another 24-week trial (data not published). HT042 has been shown to induce longitudinal bone growth by stimulation of chondrocyte proliferation and hypertrophy in growth plates [13, 14]. The mechanism underlying HT042-induced bone growth involves the stimulation of GH secretion [15], which is assumed to lead to the systemic and local production of insulin-like growth factor-1 (IGF-1) [13, 14].…”

“…HT042 has been shown to induce longitudinal bone growth by stimulation of chondrocyte proliferation and hypertrophy in growth plates [13, 14]. The mechanism underlying HT042-induced bone growth involves the stimulation of GH secretion [15], which is assumed to lead to the systemic and local production of insulin-like growth factor-1 (IGF-1) [13, 14]. This mechanism was also supported by a previous report where A. membranaceus induced GH release [16].…”