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http://dx.doi.org/10.18325/jkmr.2020.30.2.47

Experimental Study of Dohongsamul-tang (Taohongsiwu-tang) on Fracture Healing  

Ha, Hyun Ju (Department of Korean Medicine Rehabilitation, College of Korean Medicine, Daejeon University)
Oh, Min-Seok (Department of Korean Medicine Rehabilitation, College of Korean Medicine, Daejeon University)
Publication Information
Journal of Korean Medicine Rehabilitation / v.30, no.2, 2020 , pp. 47-66 More about this Journal
Abstract
Objectives The purpose of this study is to evaluate the bone healing effect of Dohongsamul-tang (Taohongsiwu-tang; DH) on femur fractured mice. Methods Mice were randomly divided into 4 groups (naive, control, positive control and DH). All groups except naive group were subjected to bone fracture on both hind limb femurs. Naive group received no treatment at all. Control group was fed with normal saline, and positive control group was orally medicated with tramadol. DH-treated group was orally medicated with DH. We analysed the levels of BMP2, COX2, Col2a1, Sox9, Runx2, and Osterix genes on 3, 7 and 14 days after fracture. Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, total cholesterol, and triglyceride levels were measured for safety assessment. Results In morphological, histological analysis, callus formation process of DH-treated group was faster than the control group. BMP2, Sox9 gene expression were significantly increased at 7 days after fracture compared to the control group. COX2, Col2a1 gene expression were significantly increased at 14 days after fracture compared to the control group. Total cholesterol was significantly increased by DH at 3 days. Triglyceride was significantly decreased by DH at 3, 7 days after fracture compared to the control group. Conclusions Dohongsamul-tang promoted bone healing process after fracture by stimulating the bone regeneration factors. And DH shows no hepatotoxicity, nephrotoxicity and serum lipid abnormality. In conclusion, it seems that DH helps to promote fracture regeneration after bone fracture by regulating gene expressions related to bone repair.
Keywords
Korean traditional medicine; Bone fractures; Fracture healing; Gene expression; Toxicity tests;
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1 Kim HW, Choi EG, Chung HJ, Joung YM, Shin DS, Cho SI. Effects of angelicae gigantis radix (AGR) on polycystic ovary induced by estradiol valerate in rats. Korea Journal of Herbology. 2011;26(1):81-5.   DOI
2 Hwang DY. New bangyakhappyeon. Seoul:Yeonglimsa. 2010:407-9, 413, 434-5, 443, 552-3.
3 Seo HJ, Kim JH, Kwak DY, Jeon SM, Ku SK, Lee JH, Moon KD, Choi MS. The effects of safflower seed powder and its fraction on bone tissue in rib-fractured rats during the recovery. Journal of Nutrition and Health. 2000;33(4):411-20.
4 Histing T, Garcia P, Holstein JH, Klein M, Matthys R, Nuetzi R, Steck R, Laschke MW, Wehner T, Bindl R, Recknagel S, Stuermer EK, Vollmar B, Wildemann B, Lienau J, Willie B, Peters A, Ignatius A, Pohlemann T, Claes L, Menger MD. Small animal bone healing models: standards, tips, and pitfalls results of a consensus meeting. Bone. 2011;49(4):591-9.   DOI
5 Frost HM. The biology of fracture healing. An overview for clinicians. Part I. Clinical Orthopaedic Related Research. 1989;11(248):283-93.
6 Kang SY, Jung HJ, Jung YB, Jang EC, Lee EY, Lee MK, Kim MK. Matrix metalloproteinase-1 and transforming growth factor-${\beta}1$ expression during distraction osteogenesis and fracture healing of the rat. The Journal of the Korean Orthopaedic Association. 2008;43(5):529-38.   DOI
7 Hawkey CJ. COX-1 and COX-2 inhibitors. Best Practice & Research Clinical Gastroenterology. 2001;15(5):801-20.   DOI
8 Jingushi S, Michael EJ, Mark EB. Genetic expression of extracellular matrix proteins correlates with histologic changes during fracture repair. Journal of Bone and Mineral Research. 1992;7(9):1045-55.   DOI
9 Lefebvre V, Huang W, Harley VR, Goodfellow PN, Crombrugghe B. SOX9 is a potent activator of the chondrocyte-specific enhancer of the pro alpha1(II) collagen gene. Molecular and Cellular Biology. 1997;17(4):2336-46.   DOI
10 Baek WY, Kim JE. Gene alterations by osteoblast-specific transcription factor osterix in postnatal bone formation. Osteoporosis. 2011;9(1):51-6.
11 Lee HS, Lee CS, Jang JS, Lee JD, Um MS. Changes of serum alkaline phosphatase and osteocalcin during fracture healing. The Journal of the Korean Orthopaedic Association. 2002;37(3):411-5.   DOI
12 The Korean Society of Laboratory Medicine. Laboratory medicine. 4th ed. Seoul:E-public. 2009:307, 318, 346.
13 Lim HC, Jeon SY. The effect of gamidohongsamul-tang (GDT) on the gene expression levels of eNOS, KLF2, ICAM-1 and VCAM-1 in HUVEC cells. The Journal of Internal Korean Medicine. 2018;39(1):1-8.   DOI
14 Chang SH, Lim EM, Lee E. Effects of Dohongsamultang on surgically induced endometriosis in rats. The Journal of Oriental Obstetrics & Gynecology. 2006;19(1):125-38.
15 Rice DP, Aberg T, Chan Y, Tang Z, Kettunen PJ, Pakarinen L, Maxson RE, Thesleff I. Integration of FGF and TWIST in calvarial bone and suture development. Development. 2000;127(9):1845-55.   DOI
16 The Korean Orthopedic Association. Orthopaedics. 7th ed. Seoul:ChoiSin medical Publishing Co. 2013:1149-86, 1474.
17 The Society of Korean Medicine Rehabilitation. Korean Rehabilitation Medicine. 4th ed. Paju:Koonja Publishing. 2015:206-10.
18 Wuqian. Yizhongjinjian. Beijing:People's Medical Publishing House. 2000:104-6.
19 The Society of Oriental Obstetrics & Gynecology. Korean obtetrics and gynecology. Seoul:Jeongdam Publisher. 2001:186-8, 221.
20 Cho KI, Kim HY, Lee SG, Sin SH, Moon BS, Ko SJ. Effects of dohongsamul-tang on the gene expression of photothrombotic ischemia mouse model. Journal of Physiology & Pathology in Korean Medicine. 2009;23(3):645-61.
21 Han GJ, Jang MW, Seong S, Kim SS. A case report of chemotherapy-induced hand-foot syndrome treated with modified dohongsamul-tang. The Journal of Internal Korean Medicine. 2018;39(2):259-67.   DOI
22 Bonnarens F, Einhorn TA. Production of a standard closed fracture in laboratory animal bone. J Orthop Res. 1984;2:97-101.   DOI
23 Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clinical Pharmacokinetics. 2004;43(13):879-923.   DOI
24 Crockett JC, Rogers MJ, Coxon FP, Hocking LJ, Helfrich MH. Bone remodelling at a glance. J Cell Sci. 2011; 124(Pt 7):991-8.   DOI
25 Min SG, Chun JS, Yong JH. The effects of pulsed ultrasound on the bone healing process in fracture model of diabetes mellitus rat. Journal of Korean Society Physical Therapy. 2006;18(2):47-58.
26 Simon AM, Manigrasso MB, O'Connor JP. Cyclo-oxygenase 2 function is essential for bone fracture healing. J Bone Miner Res. 2002;17(6):963-76.   DOI
27 Kwak MJ, Myeong HK, Lee HS, Hwang JJ. Allele frequencies of COL2A1 locus in Koreans detected by polymerase chain reaction. The Korean Journal of Legal Medicine. 1994;18(2):1-8.
28 Einhorn TA. The science of fracture healing. J Orthop Trauma. 2005;19(10 Suppl):S4-S6.   DOI
29 Park SG, Shon OJ. Impaired bone healing metabolic and mechanical causes. The Journal of the Korean Fracture Society. 2017;30(1):40-51.   DOI
30 Lee DH, Kim JW. Bone substitutes and the advancement for enhancing bone healing. The Journal of the Korean Fracture Society. 2017;30(2):102-9.   DOI
31 Oh WT, Song HK, Yang KH. Intermittent parathyroid hormone treatment for stimulation of callus formation on distal femoral fracture in elderly patients. Journal of Bone Metabolism. 2011;18(2):137-41.
32 Qian XC. Shangkebuyao. Taibei:Wen Kuang Publishing Company. 1977:70-3.
33 Qian S. Byeonzhengkimoon. Seoul:Haenglim Publishing Company. 1982:311-2.
34 Shin JY. Bangyakhappyeon commentary. Seoul:Traditional Medicine Research Center. 2000:62-4.
35 Zhu ZH. Sinpyeon dangyesimbeopbuyeo. Seoul:Daesung Publishing Company. 1982:67, 515, 533, 541.
36 Yu BS, Jung JE, Park JY, Yun JM, Lee I, Moon BS. Protective effects of dohongsamul-tang on zinc-mediated cytotoxicity in H9c2 cardiomyoblast cells. Journal of Physiology & Pathology in Korean Medicine. 2004; 18(5):1374-81.