5.2. Astragalus membranaceus Mixture (HT042)
HT042 is a mixed herbal formulation comprising the dried roots of
Phlomis umbrosa, the roots of
Astragalus membranaceus, and the stem barks of
Eleutherococcus senticosus [40][24]. The group treated with HT042 at a dosage of 100 mg/kg for four days showed a significant increase in the proximal tibia growth plate of female SD rats. Additionally, the number of 5-bromodeoxyuridine (BrdU)-positive cells in the HT042 group was significantly higher compared to that of the control group in the tibia growth plate. Moreover, the expression levels of BMP-2 and IGF-1 were notably elevated in the PZ and HZ of growth plate in the HT042-treated group. The randomized controlled trial demonstrated that supplementation with HT042 for 23 weeks increased height growth in children who had not yet reached skeletal maturation
[11][25]. This effect was attributed to elevated levels of serum IGF-1 and IGF-binding protein-3
[41][26].
5.3. Humulus japonicus Mixture (MH)
H. japonicus, commonly known as Japanese hops, is used for the treatment of inflammatory diseases
[42][27]. In an in vivo study, it was observed that nose–tail length gain, body weight gain, and femur and tibia length significantly increased in the group treated with
H. japonicus water extracts combined with garlic and watermelon powder (MH) at dosages of 100 and 300 mg/kg for 5 weeks in adolescent female SD rats.
5.4. Yukmijihwang-Tang (YJT) Herbal Formulation
Yukmijihwang-tang (YJT) contains six medicinal herbs, such as
Rehmannia glutinosa,
Cornus officinalis,
Dioscorea batatas,
Alisma orientale,
Poria cocos, and
Paeonia suffruticosa, in traditional Korean medicine (TKM)
[45][28]. YJT is widely used in TKM to treat age-related disorders, such as Alzheimer’s disease
[46][29]. An in vivo study showed that YJT, at a dosage of 300 mg/kg in the treated group, significantly increased the length of the proximal tibia in the growth plate of female SD rats.
5.5. Jaoga-Yukmiwon (JY) Herbal Formulation
Jaoga-Yukmiwon (JY) consists of the alcohol extracts of seven medicinal herbs:
Acanthopanax senticosus,
Rehmannia glutinosa,
Poria cocos,
Dioscorea japonica,
Cornus officinalis,
Cervus Nippon, and
Panax ginseng. JY is an herbal formulation from TKM used for the treatment of growth disorders
[10][30]. The administration of JY at a dosage of 100 mg/kg showed a significant increase in the tibial length and the induction of BMP-2 in the tibial growth plates in adolescent male SD rats
[49][31].
5.6. Siwu Decoction
Siwu decoction, consisting of
Angelica sinensis,
Cnidium officinale,
Paeonia lactiflora, and steam-prepared root of
Rehmannia glutinosa, has traditional uses for pain relief, anemia improvement, and blood circulation. The main ingredients responsible for these effects are quercetin, kaempferol, cytoglucide, apigenin, and stigmasterol
[50][32]. Administered as water extracts to 33-day-old SD rats twice daily for 4 days, it promoted cartilage cell proliferation and new bone formation in the growth plate.
5.7. Phlomis umbrosa
The
P. umbrosa root has been used in traditional Chinese medicine to enhance muscular and skeletal strength and to address fractures. In previous reports,
P. umbrosa was found to possess various properties, including anti-allergic, anti-inflammatory, and anti-nociceptive effects
[52][33]. These effects are likely attributed to the presence of various active compounds, such as sesamoside, shanzhiside methyl ester, chlorogenic acid, and barlerin
[53][34]. When administered orally at doses of 100 and 300 mg/kg for 10 consecutive days,
P. umbrosa root 70% ethanol extracts markedly increased longitudinal bone growth within the proximal tibial growth plate in adolescent SD female rats (5-weeks-old), consistent with findings showing a significant increase in the number of BrdU-labeled chondrocytes in the
P. umbrosa groups at doses of 100 and 300 mg/kg.
5.8. Allium fistulosum
A. fistulosum is a perennial plant species that grows globally and belongs to the Liliaceae family. Previous studies reported the effects of
A. fistulosum on antioxidant activity
[55][35]. Administering 450 mg/kg of
A. fistulosum water extracts significantly increased the length of the proximal tibial growth plate and bone mineral density in C57BL/6 mice (4-weeks-old) that were fed a diet deficient in vitamin D and calcium for 5 weeks.
5.9. Allium macrostemon
A. macrostemon, as an important medicinal and edible herb, has been used to treat some diseases for thousands of years in China
[57][36]. Steroidal saponins, a class of oligoglycosides, are the major active compounds in
A. macrostemon, and they have biological activities, including hypoglycemic, antithrombotic, and anti-inflammatory effects
[58][37]. The administration of
A. macrostemon 30% ethanol extracts at a dosage of 100 mg/kg for 10 days significantly increased the proximal tibial length of female SD rats.
5.10. Amomum villosum
A. villosum has been traditionally used to improve gastrointestinal motility in traditional medicine
[60][38]. When administered at a dosage of 500 mg/kg for 5 days,
A. villosum extracts significantly increased the length of the proximal tibial growth plate in female SD rats
[61][39]. BrdU-labeled cells were also significantly observed in the chondrocytes treated with
A. villosum extracts.
5.11. Eucommia ulmoides
E. ulmoides is well-known as a tonic medicinal herb for the treatment of bone diseases in traditional Chinese medicine
[62][40]. Geniposidic acid, geniposide, and aucubin from
E. ulmoides have been shown to increase bone metabolism
[63][41]. In the group treated with
E. ulmoides 70% ethanol extracts at a dose of 100 mg/kg for 4 days, there was a significant enhancement in the length of the proximal tibial growth plate due to the promotion of chondrogenesis in the growth plate, along with increased levels of BMP-2 and IGF-1 in adolescent female SD rats
[64][42].
5.12. Phyllostachyos caulis
P. caulis, well-known as the stem of giant timber bamboo, is used for the treatment of hypertension and cardiovascular diseases in traditional Chinese medicine
[65][43]. It has various biological effects, such as those related to inflammatory diseases
[66][44]. When administered at a concentration of 200 mg/kg of bamboo extract for 10 days to female SD rats, there was a significant increase in the total tibial length, which was attributed to the heights of the proliferative and hypertrophic zones in the tibia.
5.13. Phellodendron amurense
P. amurense is one of the major plants in traditional Chinese medicine. It has been used traditionally in folk medicine for hepatitis, dysentery, and gynaecological inflammation
[68][45].
P. amurense contains mainly isoquinoline alkaloids, such as berberine chloride
[69][46]. When administered at dosages of 100 and 300 mg/kg for 41 days,
P. amurense extracts significantly increased the length of the proximal tibial growth plate in female SD rats without changes in food intake or body weights. The levels of IGF-1 and BMP-2 in the proliferative zones of the tibial growth plate significantly increased in the
P. amurense extract-treated groups.
5.14. Velvet Antler
Velvet antler (VA), sourced from young male deer antlers, has a long history of use in Asian countries for its immune-boosting, stamina-enhancing, and bone health benefits. In a study on male SD rats (3-week-old), a 100 mg/kg dose of VA for 5 days significantly increased bone density, growth plate height, and BMP-2 expression. When applied to MG-63 cells, VA also stimulated cell proliferation, ALP activity, collagen synthesis, calcium deposition, and increased mRNA levels of collagen, ALP, and osteocalcin
[71][47].
76. Conclusions
The effectiveness of the long-term administration of therapeutic agents used for idiopathic short stature (ISS), such as recombinant human growth hormone (rhGH), aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), remains a topic of controversy. Consequently, there is an expectation of positive outcomes from easily accessible traditional herbal medicine complexes or health supplements. However, there is a lack of scientific evidence regarding the clear mechanisms of their effects or their potential toxicity. In Korea, only the
Astragalus extract mixture HT042 has been approved by the Korea Food and Drug Administration (KFDA) to promote height growth in children. Several herbal formulations based on traditional medicine have the potential to improve bone growth, although their effectiveness is controversial. Ongoing research efforts are actively working to uncover a clear mechanism, emphasizing the importance of a scientific approach.