The Impact of HT042 Herbal Formula on Longitudinal Bone Growth in Adolescent Female Rats
Abstract:
The herbal formula HT042, composed of three potent herbal extracts—Astragalus membranaceus, Phlomis umbrosa, and Eleutherococcus senticosus—has been traditionally used in Korean medicine to promote growth in children. This study investigates HT042’s effect on longitudinal bone growth using both short- and long-term rat models. The findings reveal significant increases in bone growth and chondrocyte proliferation, positioning HT042 as a promising alternative to growth hormone therapies.
Short-Term Study: Methodology and Findings
In the short-term model, three-week-old female Sprague-Dawley rats were divided into six groups: a vehicle control, HT042 (100 mg/kg), Phlomis umbrosa (100 mg/kg), Astragalus membranaceus (100 mg/kg), Eleutherococcus senticosus (100 mg/kg), and recombinant human growth hormone (rhGH) (1 IU). The treatments were administered twice daily, with the rhGH group receiving a single daily subcutaneous injection. After four days, the rats were sacrificed, and their tibias were analyzed for bone growth.
Results:
The study showed a significant increase in bone growth in the HT042 and rhGH groups, with growth rates of 433.50 ± 21.61 μm/day and 434.49 ± 15.21 μm/day, respectively, compared to 410.03 ± 17.4 μm/day in the control group. The growth plate height also increased significantly in both the HT042 (556.5 ± 21.1 μm) and rhGH (544.2 ± 21.1 μm) groups compared to the control (518.1 ± 4.1 μm).
Interestingly, the number of BrdU-positive cells, indicating proliferating chondrocytes, was 389 ± 36 cells/mm² in the HT042 group, significantly lower than the 627 ± 39 cells/mm² in the rhGH group. This suggests that HT042 may promote bone growth through mechanisms beyond cellular proliferation, potentially by enhancing chondrocyte hypertrophy and stimulating other growth factors such as Insulin-like Growth Factor-1 (IGF-1) and Bone Morphogenetic Protein-2 (BMP-2), both of which were highly expressed in the growth plates of the HT042 group.
Long-Term Study: Growth Measurements and Observations
In the long-term study, female rats were treated with HT042 or rhGH for four weeks, during which their body weight, nose-to-tail length, and nose-to-anus length were measured. While the rhGH group showed a significant increase in body weight, the HT042 group displayed comparable increases in skeletal growth. The nose-to-anus length increased to 18.5 ± 0.3 cm in the HT042 group and 18.7 ± 0.3 cm in the rhGH group, versus 18.2 ± 0.2 cm in the control group.
Discussion:
While HT042 and rhGH both enhanced bone growth rates, the exact implications for adult height remain uncertain. Growth rates do not always translate to increased final height; the mode of growth is critical. HT042 appears to enhance chondrogenic activity, possibly by increasing telomere length via the TAT2 compound found in Astragalus membranaceus, thereby promoting cellular proliferation.
Eleutherococcus senticosus, known for its anti-inflammatory properties, may also play a role by protecting chondrocytes from inflammatory damage, thereby supporting sustained bone growth.
Skeletal Growth and IGF Levels After HT042 Treatment
A separate study further supports HT042’s effectiveness in promoting bone growth. Female Sprague-Dawley rats treated with HT042 for three weeks showed significant increases in axial skeletal growth, femur length, and growth plate height. The herbal formula notably increased serum IGF-1 and IGFBP-3 levels, crucial for bone growth, without eliciting any estrogenic response—a vital factor for safe use in children.
Conclusion: A Natural Alternative to Growth Hormone?
The findings suggest that HT042 may be a viable alternative to traditional growth hormone treatments, particularly for children with short stature. While rhGH remains more potent in inducing cellular proliferation, HT042 offers a more holistic approach, potentially increasing bone growth by enhancing chondrocyte hypertrophy and stimulating local growth factors such as IGF-1 and BMP-2.
Further studies are needed to determine whether the increased growth rate observed with HT042 translates to greater adult height or merely accelerates the attainment of genetic potential. However, its ability to promote bone growth without the estrogenic side effects or gastrointestinal absorption issues associated with rhGH makes HT042 a promising candidate in pediatric growth treatments.
