Astragalus Extract Mixture HT042 Alleviates Dexamethasone-Induced Bone Growth Retardation in Rat Metatarsal Bones

被引:0
|
作者
Baek, Chae Yun [1 ]
Lee, Juni [1 ]
Lee, Donghun [1 ]
Kim, Hocheol [2 ]
机构
[1] Gachon Univ, Dept Herbal Pharmacol, Coll Korean Med, 1342 Seongnamdae Ro, Seongnam Si 13120, South Korea
[2] Kyung Hee Univ, Coll Korean Med, Dept Herbal Pharmacol, 26 Kyungheedae Ro, Seoul 02447, South Korea
关键词
HT042; dexamethasone; growth retardation; proliferation; hypertrophy; apoptosis; GLUCOCORTICOID TREATMENT; HORMONE RECEPTOR; BINDING PROTEIN; EXPRESSION; PLATE; SUPPRESSION; GH; CHILDREN;
D O I
10.3390/nu16142333
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
The most widely used synthetic glucocorticoid, dexamethasone (DEX), causes stunted growth in children when used excessively or for long periods of time; however, there are still plenty of pediatric patients require long-term treatment with DEX. As an alternative, growth hormone is used in combination, but it has side effects, a high cost, and psychological factors, and it is not satisfactory in terms of effectiveness. It is necessary to develop a safe and affordable treatment that can replace it. The Korean Food and Drug Administration approved HT042, a standardized functional food ingredient, with the claim that it can help height growth of children. In this study, it was found that HT042 activated the Indian hedgehog/parathyroid hormone-related protein signaling pathway and enhanced the number of growth hormone receptors and insulin-like growth factor-1 receptors on the growth plate surface, which were reduced by DEX treatment, and restored growth retardation. In metatarsal bone and primary chondrocyte models, it was found that HT042 can promote the length of growth plate and recover DEX-induced growth retardation. It was also found that HT042 promotes cell proliferation using bromodeoxyuridine and terminal deoxynucleotidyl transferase dUTP nick end labeling assays; moreover, we verified increased expression of GHR/IGF-1R and Ihh/PTHrP pathway activity using qRT-PCR, western blotting, and siRNA analyses to verify its direct action on the growth plate. The anti-apoptotic effect of HT042 was identified by regulating the expression of apoptotic factors such as caspase-3, Bcl2, Bclx, and Bax. These results were identified using both ex vivo and in vitro models. Our study verified that co-administration of HT042 could recover the DEX induced growth retardation
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页数:20
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