Effect of HT042, Herbal Formula, on Longitudinal Bone Growth in Spontaneous Dwarf Rats

Evidence-Based Complementary and Alternative Medicine

et al. 2017

Self Cite

Astragalus extract mixture HT042 is a standardized ingredient of health functional food approved by Korean FDA with a claim of “height growth of children.” HT042 stimulates bone growth rate and increases local IGF-1 expression in growth plate of rats which can be considered as direct stimulation of GH and its paracrine/autocrine actions. However, it remains unclear whether HT042 stimulates circulatory IGF-1 which also plays a major role to stimulate bone growth. To determine the effects on circulatory IGF-1, IGF-1 and IGFBP-3 expressions and phosphorylation of JAK2/STAT5 were evaluated in the liver after 10 days of HT042 administration. HT042 upregulated liver IGF-1 and IGFBP-3 mRNA expression, IGF-1 protein expression, and phosphorylation of JAK2/STAT5. HT042 also increased bone growth rate and proliferative zonal height in growth plate. In conclusion, HT042 stimulates bone growth rate via increment of proliferative rate by upregulation of liver IGF-1 and IGFBP-3 mRNA followed by IGF-1 protein expression through phosphorylation of JAK2/STAT5, which can be regarded as normal functioning of GH-dependent endocrine pathway.

Section: Introductionmentioning

confidence: 99%

Astragalus Extract Mixture HT042 Increases Longitudinal Bone Growth Rate by Upregulating Circulatory IGF‐1 in Rats

Evidence-Based Complementary and Alternative Medicine

et al. 2017

Self Cite

“…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 ]. Although GH is mostly known for its effects on growth plate cartilage, it also stimulates osteoblast proliferation and activity, thereby increasing trabecular bone formation [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that the dose and duration of the treatment chosen for this study were not sufficient to be biologically active. As HT042 has been suggested to stimulate GH secretion [ 15 ], it is premature to conclude that HT042 does not increase cortical bone mass or thickness. However, further studies are needed to address this issue.…”

Section: Discussionmentioning

confidence: 99%

“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

Song

Evidence-Based Complementary and Alternative Medicine

et al. 2017

Self Cite

Astragalus extract mixture HT042 is a standardized multiherbal mixture comprising Astragalus membranaceus, Eleutherococcus senticosus, and Phlomis umbrosa, which has proven to promote children's height growth. The aim of this study was to investigate the effects of HT042 on longitudinal bone growth, bone mass, and bone microstructure in growing rats using a high-resolution microcomputed tomography system. Four-week-old female rats were fed an HT042-containing diet for 2 weeks. Tibial length was measured at baseline and weekly in vivo. At the end of the study, volumetric bone mineral density (vBMD) and microarchitectural parameters were estimated in the trabecular and cortical bone of the tibia. Tibial length gain was significantly increased by HT042 compared to that reported with the control diet. In the proximal tibial metaphysis, HT042-treated rats had significantly higher trabecular vBMD, bone volume fraction, and trabecular number and lower trabecular separation, trabecular pattern factor, and structure model index values than control rats did. Total cross-sectional area and bone area of the cortical bone in the tibial diaphysis also increased. These findings suggest that HT042 increases longitudinal bone growth rate, improves trabecular bone mass, and enhances the microarchitecture of trabecular and cortical bone during growth.

“…Maxim., is an herbal mixture that has been used to strengthen bones and muscles from traditional Korean medicine. HT042 enhances longitudinal bone growth in in vivo models by stimulating cell proliferation in the epiphyseal plate and inducing the expression of insulin-like growth factor-1 (IGF-1) without estrogenic response (Kim et al, 2013;Kim et al, 2012;Kim et al, 2010). HT042 is approved by Korean Food and Drug Administration with a claim 'HT042 can help height growth of children' (KFDA, 2016) because it was effective in the unpublished randomized controlled trial for 12 weeks in school-aged children with mild short stature.…”

Section: Introductionmentioning

confidence: 99%

Effects of Astragalus Extract Mixture HT042 on Height Growth in Children with Mild Short Stature: A Multicenter Randomized Controlled Trial

Song

et al. 2017

Phytotherapy Research

Self Cite

HT042 is a standardized functional food ingredient approved by Korean Food and Drug Administration with a claim 'HT042 can help height growth of children'. We aimed to evaluate the safety and efficacy of HT042 on height growth in children with mild short stature. A multicenter, randomized, double-blind, placebo-controlled parallel study was performed on children aged 6-8 years with height ranked below the 25th percentile. In 129 children, height gain was significantly higher in HT042 group than placebo group after 24 weeks (mean difference, 0.29 cm; 95% CI, 0.01 to 0.57 cm; p = 0.027). The difference was elevated when the efficacy analysis was restricted to children below the 10th percentile (mean difference, 0.45 cm; 95% CI, 0.04 to 0.87 cm; p = 0.031). Because bone age advancement was lower in HT042 group, height standard deviation score gain for bone age was higher in HT042 group and the difference was significant in children below the 10th percentile (mean difference, 0.20 score; 95% CI, 0.00 to 0.39 points; p = 0.045). Serum IGF-1 and IGFBP-3 levels were significantly increased compared with baseline within HT042 group, but group difference was not significant. HT042 supplementation helped to increase height growth in children without skeletal maturation and was more effective in much shorter children. The effects might be mediated by increases in serum IGF-1 and IGFBP-3 levels. Copyright © 2017 John Wiley & Sons, Ltd.