The Herbal Formula HT042 Induces Longitudinal Bone Growth in Adolescent Female Rats

Abstract

The effect of HT042, a blend of three herbal extracts, on longitudinal bone growth was investigated in short- and long-term rat models. In the short-term model, we divided female Sprague-Dawley rats (3 weeks old) into six groups, according to treatment: vehicle, HT042 (100 mg/kg), Phlomis umbrosa (100 mg/kg), Astragalus membranaceus (100 mg/kg), and Eleutherococcus senticosus (100 mg/kg) were administered twice daily, and recombinant human growth hormone (rhGH) (1 IU) was subcutaneously injected once daily. Treatments were maintained for 4 days in each case. On day 3, tetracycline (20 mg/kg) was injected intraperitoneally (20 mg/kg) to form the fluorescent band on the growth plates. On days 2-4, 5-bromo-2'-deoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally to label proliferating cells. On day 5, the tibias were dissected and fixed in 30% sucrose. Dehydrated bone was sectioned at a thickness of 40 μm and observed. The bone growth in groups administered HT042 and rhGH was significantly increased to 433.50 ± 21.61 and 434.49 ± 15.21 μm/day, respectively, from 410.03 ± 17.4 μm/day (control). The height of the growth plates in the HT042 and rhGH groups was also significantly increased to 556.5 ± 21.1 and 544.2 ± 21.1 μm (P < .05), respectively, from 518.1 ± 4.1 μm (normal). The number of BrdU-positive cells in chondrocytes of the HT042 and rhGH groups was increased to 389 ± 36 and 627 ± 39 cells/mm² (P < .001), respectively, from 264 ± 17 cells/mm² (control). Insulin-like growth factor-1 and bone morphogenetic protein-2 in the HT042 group were highly expressed in the growth plate. In the long-term rat model, the body weight, nose-tail length, and nose-anus length were measured by microknemometry for 4 weeks. The body weight of the rhGH group was significantly increased. The nose-anus length of the HT042 and rhGH groups was significantly greater at 18.5 ± 0.3 and 18.7 ± 0.3 cm compared to 18.2 ± 0.2 cm (control).

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.…”

“…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].…”

Osteoprotective Medicinal Plants - Part 1 (A Human Clinical Evidence-Based Review)

“…alkaline phosphatase) , without affecting the uterus weight, and serum estradiol level in OVX-R (Lim et al, 2013). A herbal formula HT042, consisting of ES, Phlomis umbrosa, and Astragalus membranaceus, which is used in traditional Korean medicine to stimulate growth of children with short stature, induced longitudinal bone growth in adolescent or adult female rats (Kim et al, , 2010. HT042 has also increased the expression of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and bone morphogenetic protein-2 in the growth plate.…”

Effect of combined extract of Hansogdan (Phlomis umbrosa) and Dalgaebi (Commelina communis) as a milk additive for enhancing the growth of physical height in vivo

“…3). Kim et al (12) showed that 100 mg/kg dose of mixed herbal extract containing 19.7% of 70% ethanol extract of hansogdan for 4 weeks administration with 4-week-old SD rats had significant N-A growth enhancing effect (p<0.05), but N-T growth was not different from that of normal control at the completion of study. However, the mixed extract of hansogdan and dalgaebi showed significant growth enhancing effect for both N-T and N-A lengths compared to milk control group (Fig.…”