Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2017 | Research article

The Korean herbal formulation Yukmijihwangtang stimulates longitudinal bone growth in animal models

Authors: Sung-Min Cho, Sun Haeng Lee, Donghun Lee, Ji Hong Lee, Gyu Tae Chang, Hocheol Kim, Jin Yong Lee

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Abstract

Background

Yukmijihwangtang (YJT) is a traditional Korean medicine that has been used to treat kidney-yin deficiency symptoms such as dizziness and tinnitus. In addition, because it is also thought to nourish kidney-yin, it has been used to treat short stature from congenital deficiency. This study evaluated the effects of YJT on longitudinal bone growth in rats.

Methods

Female adolescent rats were randomly assigned to groups that received distilled water (per os [p.o.] twice a day; control), recombinant human growth hormone (rhGH; 20 μg/kg, subcutaneous [s.c.] once a day), or two different doses of YJT (100 or 300 mg/kg, p.o. twice a day). In each group, treatment was maintained for 4 days. Rats were injected intraperitoneally with 5-bromo-2’-deoxyuridine (BrdU; 50 mg/kg) to label proliferating chondrocytes on days 2 – 4. Tetracycline hydrochloride (20 mg/kg) was injected intraperitoneally to form fluorescent bands on the growth plates on day 3 for measuring the longitudinal bone growth rate. Expression of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate was identified using immunohistochemistry.

Results

There was a significant increase in the rate of bone growth in the 300 mg/kg YJT group (523.8 ± 23.7 μm/day; P < 0.05) compared to the control group (498.0 ± 23.8 μm/day), while the 100 mg/kg YJT group exhibited a non-significant increase. The number of BrdU-positive cells in the chondrocytes of the rhGH-treated group exhibited a significant increase (103.8 ± 34.2 cells/mm²) compared to that of the control group (70.3 ± 19.7 cells/mm²), while the 300 mg/kg YJT group had a non-significant increase. Additionally, IGF-1 and BMP-2 were highly expressed in the growth plate in the 300 mg/kg YJT and rhGH groups.

Conclusions

YJT increased the longitudinal bone growth rate by stimulating chondrocyte proliferation with increasing increments of local IGF-1 and BMP-2 expression. Based on these findings, YJT may be a therapeutic candidate for the treatment of growth retardation during adolescence.

Yuhong H, Qian L, Yu L, Yingqiang Z, Yanfen L, Shujing Y, Shufang Q, Lanjun S, Shuxuan Z, Baohe W. An n-of-1 trial service in clinical practice: testing the effectiveness of liuwei dihuang decoction for kidney-Yin deficiency syndrome. Evid Based Complement Alternat Med. 2013;2013:827915.CrossRefPubMedPubMedCentral

Zhou W, Cheng X, Zhang Y. Effect of liuwei dihuang decoction, a traditional Chinese medicinal prescription, on the neuroendocrine immunomodulation network. Pharmacol Ther. 2016;162:170–8.CrossRefPubMed

Xia B, Xu B, Sun Y, Xiao L, Pan J, Jin H, Tong P. The effects of liuwei dihuang on canonical Wnt/beta-catenin signaling pathway in osteoporosis. J Ethnopharmacol. 2014;153(1):133–41.CrossRefPubMed

Huang Y, Zhang H, Yang S, Qiao H, Zhou W, Zhang Y. Liuwei Dihuang decoction facilitates the induction of long-term potentiation (LTP) in senescence accelerated mouse/prone 8 (SAMP8) hippocampal slices by inhibiting voltage-dependent calcium channels (VDCCs) and promoting N-methyl-d-aspartate receptor (NMDA) receptors. J Ethnopharmacol. 2012;140(2):384–90.CrossRefPubMed

Tseng YT, Chang FR, Lo YC. The Chinese herbal formula Liuwei dihuang protects dopaminergic neurons against Parkinson’s toxin through enhancing antioxidative defense and preventing apoptotic death. Phytomedicine. 2014;21(5):724–33.CrossRefPubMed

Nair SV, Zhang J, Wang Y. Ethanol extract of Liuwei Dihuang reduces weight gain and visceral fat in obese-prone CD rats fed a high-fat diet. Exp Biol Med (Maywood). 2014;239(5):552–8.CrossRef

Perry B, Zhang J, Sun C, Saleh T, Wang Y. Liuwei dihuang lowers body weight and improves insulin and leptin sensitivity in obese rats. Evid Based Complement Alternat Med. 2012;2012:847167.CrossRefPubMed

Shin IS, Lee MY, Ha HK, Seo CS, Shin HK. Inhibitory effect of Yukmijihwang-tang, a traditional herbal formula against testosterone-induced benign prostatic hyperplasia in rats. BMC Complement Altern Med. 2012;12:48.PubMedPubMedCentral

Lin L, Wang Q, Yi Y, Wang S, Qiu Z. Liuwei dihuang pills enhance the effect of western medicine in treating diabetic nephropathy: a meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2016;2016:1509063.PubMedPubMedCentral

10.

Lee MS. Effect of Bojungikki-tang on the bone growth in adolescent rats. Seoul: Kyung Hee Univ; 2012.

11.

Lee J, Lee S, Son J, Keum S, Leem K. Effects of Cheunggyeongsamul-tang extract on longitudinal bone growth in adolescent female rats. Kor J Herbology. 2009;24(4):149–57.

12.

Leem K, Park SY, Lee DH, Boo YM, Cho KH, Lim J, Jeon H, Park HJ, Chung JH, Kim H. Effects of Jaoga-Yukmiwon(R), a Korean herbal medicine, on chondrocyte proliferation and longitudinal bone growth in adolescent male rats. Phytother Res. 2003;17(9):1113–6.CrossRefPubMed

13.

Kim KB, Kim DG, Kim YH, Kim JH, Min SY, Park EJ, Baek JH, Sung HK, Yu SA, Lee SY, et al. Pediatrics of Korean medicine. Seoul: Euisungdang; 2015.

14.

Jin UH, Kim DI, Lee TK, Lee DN, Kim JK, Lee IS, Kim CH. Herbal formulation, Yukmi-jihang-tang-jahage, regulates bone resorption by inhibition of phosphorylation mediated by tyrosine kinase Src and cyclooxygenase expression. J Ethnopharmacol. 2006;106(3):333–43.CrossRefPubMed

15.

Park BM, Soh KS, Jeong CG. Effects of Yukmiziwhang-whan on the growth of rats. Kor J Orient Prev Med Soc. 2003;7(2):23–33.

16.

Xue YM, Luo R, Zhu B, Zhang Y, Pan YH, Li CZ. Effects of liuwei dihuang pills on expressions of apoptosis-related genes bcl-2 and Bax in pancreas of OLETF rats. Zhong Xi Yi Jie He Xue Bao. 2005;3(6):455–8.CrossRefPubMed

17.

Lui JC, Baron J. Mechanisms limiting body growth in mammals. Endocr Rev. 2011;32(3):422–40.CrossRefPubMedPubMedCentral

18.

Brem G, Wanke R, Wolf E, Buchmuller T, Muller M, Brenig B, Hermanns W. Multiple consequences of human growth hormone expression in transgenic mice. Mol Biol Med. 1989;6(6):531–47.PubMed

19.

Rol De Lama MA, Perez-Romero A, Tresguerres JA, Hermanussen M, Ariznavarreta C. Recombinant human growth hormone enhances tibial growth in peripubertal female rats but not in males. Eur J Endocrinol. 2000;142(5):517–23.CrossRefPubMed

20.

Wong RW, Hagg U, Samaranayake L, Yuen MK, Seneviratne CJ, Kao R. Antimicrobial activity of Chinese medicine herbs against common bacteria in oral biofilm. A pilot study. Int J Oral Maxillofac Surg. 2010;39(6):599–605.CrossRefPubMed

21.

Duyar I, Pelin C. Body height estimation based on tibia length in different stature groups. Am J Phys Anthropol. 2003;122(1):23–7.CrossRefPubMed

22.

van der Eerden BC, Karperien M, Wit JM. Systemic and local regulation of the growth plate. Endocr Rev. 2003;24(6):782–801.CrossRefPubMed

23.

Qian Y. Key to Therapeutics of Children’s Diseases. In. China; 1119.

24.

Hansson LI, Stenstrom A, Thorngren KG. Skeletal deposition and toxicity of methacycline. Nature. 1968;219(5154):624–5.CrossRefPubMed

25.

Emons J, Chagin AS, Savendahl L, Karperien M, Wit JM. Mechanisms of growth plate maturation and epiphyseal fusion. Horm Res Paediatr. 2011;75(6):383–91.CrossRefPubMed

26.

Chen G, Deng C, Li YP. TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci. 2012;8(2):272–88.CrossRefPubMedPubMedCentral

27.

Pizette S, Niswander L. BMPs are required at two steps of limb chondrogenesis: formation of prechondrogenic condensations and their differentiation into chondrocytes. Dev Biol. 2000;219(2):237–49.CrossRefPubMed

28.

Sakou T. Bone morphogenetic proteins: from basic studies to clinical approaches. Bone. 1998;22(6):591–603.CrossRefPubMed

29.

Yazaki Y, Matsunaga S, Onishi T, Nagamine T, Origuchi N, Yamamoto T, Ishidou Y, Imamura T, Sakou T. Immunohistochemical localization of bone morphogenetic proteins and the receptors in epiphyseal growth plate. Anticancer Res. 1998;18(4A):2339–44.PubMed

30.

Hallahan AR, Pritchard JI, Chandraratna RA, Ellenbogen RG, Geyer JR, Overland RP, Strand AD, Tapscott SJ, Olson JM. BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect. Nat Med. 2003;9(8):1033–8.CrossRefPubMed

31.

Wang EA, Rosen V, D’Alessandro JS, Bauduy M, Cordes P, Harada T, Israel DI, Hewick RM, Kerns KM, LaPan P, et al. Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci U S A. 1990;87(6):2220–4.CrossRefPubMedPubMedCentral

32.

De Luca F, Barnes KM, Uyeda JA, De-Levi S, Abad V, Palese T, Mericq V, Baron J. Regulation of growth plate chondrogenesis by bone morphogenetic protein-2. Endocrinology. 2001;142(1):430–6.PubMed

33.

Klaus G, Jux C, Fernandez P, Rodriguez J, Himmele R, Mehls O. Suppression of growth plate chondrocyte proliferation by corticosteroids. Pediatr Nephrol. 2000;14(7):612–5.CrossRefPubMed

34.

Isaksson OG, Lindahl A, Nilsson A, Isgaard J. Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev. 1987;8(4):426–38.CrossRefPubMed

35.

Wang J, Zhou J, Cheng CM, Kopchick JJ, Bondy CA. Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinol. 2004;180(2):247–55.CrossRefPubMed

36.

Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, et al. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002;110(6):771–81.CrossRefPubMedPubMedCentral

37.

Abad V, Meyers JL, Weise M, Gafni RI, Barnes KM, Nilsson O, Bacher JD, Baron J. The role of the resting zone in growth plate chondrogenesis. Endocrinology. 2002;143(5):1851–7.CrossRefPubMed

38.

Farnum CE, Wilsman NJ. Determination of proliferative characteristics of growth plate chondrocytes by labeling with bromodeoxyuridine. Calcif Tissue Int. 1993;52(2):110–9.CrossRefPubMed

39.

Alcantara EH, Shin MY, Sohn HY, Park YM, Kim T, Lim JH, Jeong HJ, Kwon ST, Kwun IS. Diosgenin stimulates osteogenic activity by increasing bone matrix protein synthesis and bone-specific transcription factor Runx2 in osteoblastic MC3T3-E1 cells. J Nutr Biochem. 2011;22(11):1055–63.CrossRefPubMed

40.

Lee JW, Kobayashi Y, Nakamichi Y, Udagawa N, Takahashi N, Im NK, Seo HJ, Jeon WB, Yonezawa T, Cha BY, et al. Alisol-B, a novel phyto-steroid, suppresses the RANKL-induced osteoclast formation and prevents bone loss in mice. Biochem Pharmacol. 2010;80(3):352–61.CrossRefPubMed

41.

Hardin DS. Treatment of short stature and growth hormone deficiency in children with somatotropin (rDNA origin). Biologics. 2008;2(4):655–61.PubMedPubMedCentral

42.

Laron Z. Growth hormone therapy: emerging dilemmas. Pediatr Endocrinol Rev. 2011;8(4):364–73.PubMed

43.

Gubitosi-Klug RA, Cuttler L. Idiopathic short stature. Endocrinol Metab Clin North Am. 2005;34(3):565–80. viii.CrossRefPubMed

Title: The Korean herbal formulation Yukmijihwangtang stimulates longitudinal bone growth in animal models
Authors: Sung-Min Cho
Sun Haeng Lee
Donghun Lee
Ji Hong Lee
Gyu Tae Chang
Hocheol Kim
Jin Yong Lee
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-017-1651-1

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

The Korean herbal formulation Yukmijihwangtang stimulates longitudinal bone growth in animal models

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Sijunzi Decoction attenuates 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats and ameliorates TNBS-induced claudin-2 damage via NF-κB pathway in Caco2 cells

Anti-influenza virus activity of extracts from the stems of Jatropha multifida Linn. collected in Myanmar

Neuroprotective properties of curcumin in toxin-base animal models of Parkinson’s disease: a systematic experiment literatures review

Phytochemical analysis and in vitro anthelmintic activity of Lophira lanceolata (Ochnaceae) on the bovine parasite Onchocerca ochengi and on drug resistant strains of the free-living nematode Caenorhabditis elegans

Herbal formula SC-E1 suppresses lipopolysaccharide-stimulated inflammatory responses through activation of Nrf2/HO-1 signaling pathway in RAW 264.7 macrophages

Assessing the recovery from prerenal and renal acute kidney injury after treatment with single herbal medicine via activity of the biomarkers HMGB1, NGAL and KIM-1 in kidney proximal tubular cells treated by cisplatin with different doses and exposure times