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http://dx.doi.org/10.18325/jkmr.2019.29.4.1

The Effect of Gyejibokryunghwan on Fracture Union in Tibia-fractured Rats  

Yoon, Jeong-Won (Department of Rehabilitation Medicine of Korean Medicine, College of Oriental Medicine, Semyung University)
Kim, Soon-Joong (Department of Rehabilitation Medicine of Korean Medicine, College of Oriental Medicine, Semyung University)
Publication Information
Journal of Korean Medicine Rehabilitation / v.29, no.4, 2019 , pp. 1-14 More about this Journal
Abstract
Objectives The object of this study was to assess the effect of Gyejibokryunghwan (GBH) on anti-oxidant and anti-inflammatory activities in RAW 264.7 cells and on factors associated with fracture union in tibia-fractured rats. Methods The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity was measured to assess anti-oxidant activity. The production of nitric oxide (NO), interleukin-6 (IL-6), interleukin-$1{\beta}$ ($IL-1{\beta}$) and tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) in the RAW 264.7 cells were measured to assess anti-inflammatory activity. The production of osteocalcin, calcitonin, carboxy-terminal telepeptides of type II collagen (CTXII), transforming growth factor-${\beta}$ ($TGF-{\beta}$), bone morphogenetic protein-2 (BMP-2) in serum of tibia-fractured rats were measured to assess the effects of fracture union. X-rays were taken every two weeks from 0 to 4th week to assess fracture union effect. Results DPPH radical scavenging activity of GBH was increased according to concentration of GBH in RAW 264.7 cell. NO, prostaglandin $E_2$ ($PGE_2$), IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were significantly decreased, indicating anti-inflammatory effect. Osteocalcin, calcitonin, $TGF-{\beta}$ were significantly increased in the experimental groups. CTXII was significantly decreased in the experimental groups. BMP-2 was not significantly changed in the experimental groups. The X-ray showed that the experimental group has better healing effects on tibia-fractured rats than control group. Conclusions From above result, GBH has an effect on anti-oxidant, anti-inflammatory activities in RAW 264.7 cells. GBH showed significant results in factors related with fracture union and radiologic examination. In conclusion, GBH can help fracture union and it well be expected to be used actively in clinics.
Keywords
Gyejibokryunghwan; Anti-oxidation; Anti-inflammatory; Fracture;
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1 Dishowitz MI, Mutyaba PL, Takacs JD, Barr AM, Engiles JB, Ahn J, Kut D. Systemic inhibition of canonical notch signaling results in sustained callus inflammation and alters multiple phases of fracture healing. PLoS One. 2013;8:e68726.   DOI
2 Kim DY. Biochemical markers of bone turnover. Korean Journal Nuclear Medicine. 1999;33(4):341-51.
3 Lee HS, Lee CS, Jang JS, Lee JD, Um SM. Changes of serum alkaline phosphatase and osteocalcin during fracture healing. Journal of the Korean Orthopaedic Association. 2002;37(3):6, 411-5.
4 Leung KS, Fung KP, Sher AH, Li CK, Lee KM. Plasma bone specific alkaline phosphatase as an indicator of osteoblastic activity. Journal of Bon Joint Surgery. 1993;75-B:288-92.   DOI
5 Sandberg MM, Aro HT, Vuorio EI. Gene expression during bone repair. Clinical Orthopaedics and Related Research. 1993;289:292-312.
6 Lane NE. The osteoporosis book. New York: Oxford University Press. 1999:19-31.
7 Kim SW. Clinical endocrinology of calcitonin. Journal of Korean Society of Endocrinology. 1991;6(2):117.
8 Austin LA, Heath HH. Calcitonin: physiology and pathophysiology. New England Journal of Medicine. 1981;304:269-78.   DOI
9 Knetter SM, Baxa TJ, Chung KY, Johnson BJ, Minton JE. Steroid implants and markers of bone turnover in steers. South African Journal of Animal Science. 2012;(42)3:249-55.
10 Cho TJ, Lee KS. Bone graft substitute. Journal of Korean Society. 2006;19(1):109-16.
11 Jingushi S, Scully SP, Joyce ME, Sugioka Y, Bolander ME. Transforming growth factor-beta 1 and fibroblast growth factors in rat growth plate. Journal of Orthopaedic Research. 1995;13:761-8.   DOI
12 Rosen DM, Stempien SA, Thompson AY, Brennan JE, Ellingsworth LR, Seyedin SM. Differentiation of rat mesenchymal cells by cartilage-inducing factor enhanced phenotypic expression by dihydrocytochalasin B. Experimental Cell Research. 1986;165:127-38.   DOI
13 Bostrom MP1, Lane JM, Berberian WS, Missri AA, Tomin E, Weiland A, Doty SB, Glaser D, Rosen VM. Immunolocalization and expression of bone morphogenetic proteins2 and 4 in fracture healing. Journal of Orthopaedic Research. 1995;13(3):357-67.   DOI
14 Hogan BL. Bone morphogenetic proteins in development. Current Opinion in Genetics & Development. 1996;6(4):432-8.   DOI
15 Roark EF, Greer K. Transforming growth factor-${\beta}$ and bone morphogenetic protein-2 act by distinct mechanisms to promote chick limb cartilage differentiation in vitro. Dev Dyn. 1994;200:103-16.   DOI
16 The Korean Fracture Society. Principles of fracture management. Seoul:Panmuneducation. 2013:3,10,40.
17 Seoul National University College of Medicine Departmet of Orthopaedic. Textbook of fractures and joint injuries. Seoul:Koonja Publishing Company. 2001:105.
18 The Korean Orthopaedic Association. Orthopaedics. 7th ed. Seoul:ChoiSin Medical Publishing Co. 2013:94-9, 1153-75.
19 Park MS. Fracture and dislocation. Seoul:Korea Medical Book Publishing Company. 2000:11-2.
20 The Society of Korean Medicine Rehabilitation. Korean Rehabilitation Medicine. 4th ed. Paju:Koonja Publishing. 2015:206-9.
21 Jang JK. Jung-gyeongjeonseo. Seoul:Daeseong. 1989:427.
22 Kim YG, Park CG, Kim DC, Baek SH. A study on inhibitory effects of gaejiboknyunghwan on growth of uterine cancer cell and activity of MAP kinase. Journal of Oriental Obstetrics & Gynecology. 2002;15(1):31-43.
23 Kim JH, Baek SH. A study on inhibitory effects of gaejiboknyunghwan on growth of uterine myoma cell and activity of MAP kinase. Journal of Oriental Obstetrics & Gynecology. 2001;14(2):85-101.
24 Yasui T, Matsuzaki T, Ushigoe K, Kuwahara A, Maegawa M, Furumoto H, Aono T, Irahara M. Stimulatory effect of the herbal medicine keishi-bukuryo-gan on a cytokine-induced neutrophil chemoattractant, in rat ovarian cell culture. American Journal of Reproductive Immunology. 2003;50(1):90-7.   DOI
25 Lee CH. The effects of kyeji-bokryung-hwan on wound healing in muscle contusion-induced mouse [dissertation]. Daejeon (KR):Daejeon University; 2016.
26 Sekiya N, Goto H, Tazawa K, Oida S, Shimada Y, Terasawa K. Keishi-bukuryo-gan preserves the endothelium dependent relaxation of thoracic aorta in cholesterol-fed rabbit by limiting superoxide generation. Phytotherapy Research. 2002;16(6):524-8.   DOI
27 Kim SH, Moon JM. Effects of kyejibokryounghwan, jeodangtang, kyejibokryounghwan & jeodangtangon on intravasclar coagulation induced by endotoxin in rats. Korea Institute of Science and Technology Information. 1996;4(2):91-103.
28 Takahashi Y, Soejima Y, Kumagai A, Watanabe M, Uozaki H, Fukusato T. Japanese herbal medicines shosaikoto, inchinkoto, and juzentaihoto inhibit high-fat diet-induced nonalcoholic steatohepatitis in db/db mice. Pathology International. 2014;64(10):490-8.   DOI
29 Lee SK, Kim HG, Ahan JC, Kim JG, Chung TW, Moon JY, Park SD, Kim JK, Choi DY, Kim CH, Park WH. Effect of geijibokryunghwan on human hepatocarcinoma cells. Journal of Oriental Physiology & Pathology. 2003;17(2):568-73.
30 Jung H, Lee EJ, Oh MS. The effects of gyejibokryeong-hwan for wound healing after skin suture. J Korean Med Rehabil. 2016;26(2):29-50.   DOI
31 Heo J. Donguibogam. Seoul:Namsandang. 1976:487, 490-1, 614, 712, 727.
32 Hole JW. Human anatomy and physiology. Dubuque: W.C. Brown Publishers. 1993:170-227.
33 Seo HJ, Kim JH, Kwak DY, Jeon SM, Ku SK, Lee JH, Moon KD, Choi MS. Effects of safflower seed powder and its fraction in bone tissue in rib-fractured rats during the recovery. Journal of Nutrition and Health. 2000;33(4):411-20.
34 Vinay K, Abul A, Nelson F, Richard M. Pathology. Seoul:E public. 2009;809.
35 Wang D. Oedaebiyo. Seoul:Sungbosa. 1975:749-50.
36 Wang SG. Clinical application of gyejibokryunghwan. The Jounal of Unnam China Medical. 1980;6:41-2.
37 Oh G. Uijonggeumgam. Seoul:Bupin Publishing Company. 2006:1250.
38 Jeon SC. Sanggwaboyo. Seoul:Iljung Publishing Company. 1992:176.
39 The Oriental Pathology Compilation Committee. Oriental Pathology. Yongin:Hanuimoonhwa Publishing Company. 2010:118.
40 The Korean Medicine University Herbology Compilation Committee. Herbology. Seoul:Yeonglim Publishing Company. 2007:154-5, 235-8, 345-7, 462-3.
41 Park B, Yun KJ, Jung JY, You SS, Lee JA, Choi JA, Kang BK. Conceptualization andutilization of blood stasis syndrome among doctors of korean medicine: results of a web-based survey. American Journal of Translational Research. 2014;6(6):857-68.
42 Sheweita SA, Khoshhal KI. Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. Current Drug Metabolism. 2007;8(5):519-25.   DOI
43 Fu S, Gebicki S, Jessep W, Gebicki JM, Dean RT. Biological fate of amino acid, peptide and protein hydroperoxides. Bichem J. 1995;31(3):821-7.
44 Kim SJ. The effects of corydalis rhizoma on the cultured osteoblast damaged by reactive oxygen species [dissertation]. Wonkwang (KR):Wonkwang University; 2001:21-7.
45 Blois MS. Antioxidant determincation by the use of a stable free radical. Nature. 1958;181:1199-200.   DOI
46 Kimble RB, Vannice JL, Bloedow DC, Thompson RC, Hopfer W, Kung VT, Brownfield C, Pacifici R. Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovarietomized rats. Journal of Clinical Investigation. 1994;93:1959-67.   DOI
47 Robertson RP. Harrison's principles of internal medicine. New York: McGraw-Hill. 1994:431-5.
48 Kon T, Cho TJ, Aizawa T, Nooh N, Graves D, Gerstenfeld LC, Einhorn TA. Expresion of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. Journal of Bone and Mineral Research. 2001;16:1004-14.   DOI
49 Park JS, Jung SH. Effects of sandalwood essential oil on the iNOS expression and proinflammatory cytokine production. Yakhak Hoeji. 2013;57:70-5.
50 Weisz A, Cicatiello L, Esumi H. Regulation of the mouse inducible type nitric oxide synthase gene promotor by interferon-gamma, bacterial lipopolysaccharide and NGmonomethyl-L-arginine, Biochem J. 1996;316(1):209.   DOI
51 Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment on rheumatoid arthritis. Lancet. 2007;370(9602):1861-74.   DOI
52 Centrella M, Mccarthy TL, Canalie E. Tumor necrosis factor-alpha inhibits collagen synthesis and alkaline phosphatase activity independently of its effect on deoxyribonucleic acid synthesis in osteoblast-enriched bone cell cultures. Endocrinology. 1988;123(3):1442-8.   DOI
53 Aizawa T, Kon T, Einhorn T, Gerstenfeld LC. Induction of apoptosis in chondrocytes by tumor necrosis factoralpha. Journal of Orthopaedic Research. 2001;19:785-96.   DOI
54 Pfeilschifter J, Chenu C, Bird A, Mundy GR, Roodman GD. Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. Journal of Bone and Mineral Research. 1989;4(1):113-8.   DOI
55 Bang SJ, Kim IS, Kim OS, Kim YJ, Jung HJ. IL-6 gene promoter polymorphisms in korean generalized aggressice periodontitis patients. Journal of the Korean Academy of Periodontology. 2008;38:579-88.   DOI