Protective Effects of Cinnamomi Ramulus Herbal Acupuncture on $\beta$-cell Damage of Streptozotocin-induced Diabetic Rat

계지약침(桂枝藥鍼)이 Streptozotocin 유도 당뇨 흰쥐의 췌장세포 손상에 미치는 보호 효과

  • Seo, Chang-Wan (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Lee, Sang-Hoon (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Park, Dong-Suk (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Kang, Sung-Keel (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University)
  • 서창완 (경희대학교 한의과대학 침구학교실) ;
  • 이상훈 (경희대학교 한의과대학 침구학교실) ;
  • 박동석 (경희대학교 한의과대학 침구학교실) ;
  • 강성길 (경희대학교 한의과대학 침구학교실)
  • Received : 2009.09.04
  • Accepted : 2009.11.17
  • Published : 2009.12.20

Abstract

Objectives : For evaluation of preventive and anti-diabetic activities of Cinnamomi ramulus(CR) herbal acupuncture on pancreatic islet damage in streptozotocin(STZ)-induced diabetic rat. Methods : CR herbal acupuncture was performed at Bisu($BL_{20}$) for 3 weeks subcutaneously starting1 week before STZ i.p. injection. SD rats were divided into four groups(n=10 for each group); 1) NC group, non-treated normal control group, 2) STZ group, STZ administered control group, 3) CR125 group, CR(125mg/kg) + STZ administered group, and 4) CR250 group, CR(250mg/kg) + STZ administered group. Results : Both of CR250 and CR125 groups showed increase in insulin secretion and decrease in the level of serum triglyceride and non-esterified fatty acid in a dose-dependent manner compared to the STZ group. Only CR250 group showed decrease in the levels of glucose and total cholesterol compared to the STZ group. CR herbal acupuncture prevents $\beta$-cell damage of pancreatic islet, showing round figure on the sections of the pancreas. In the pancreatic cells, expressions of iNOS, JNK-2, P-JNK-1/2 and ERK-1/2 were decreased compared to the STZ group. CR herbal acupuncture solution did not show any cytotoxicity by MTS assay and inhibited expressions of iNOS and COX-2 in the STZ-induced diabetic rats. Conclusions : Therefore, we suggest that CR herbal acupuncture may act as a prophylactic as well as a therapeutic modality for diabetes mellitus.

Keywords

References

  1. Park YS, Eisenbarth GS. Natural history of type 1 diabetes. In: S Taylor, D LeRoith, J Olefsky etc. Textbook of diabetes mellitus. Philadelphia and New York : Lippincort Raven Company. 2000 : 2-39.
  2. Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes. 1965 ; 14 : 619-33. https://doi.org/10.2337/diab.14.10.619
  3. Sibley RK, Sutherland DE, Goetz F, Michael AF. Recurrent diabetes mellitus in the pancreas iso-and allograft. A light and electron microscopic and immunohisto-chemical analysis of four cases. Lab Invest. 1985 ; 53 : 131-44.
  4. Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PGF, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. 1985 ; 313 : 353-60. https://doi.org/10.1056/NEJM198508083130604
  5. Mandrup-Poulsen T, Bendtzen K, Nielsen H, Bendixen G, Nerup J. Cytokines cause functional and structural damage to isolated islets of Langerhans. Allergy. 1965 ; 40 : 424-9. https://doi.org/10.1111/j.1398-9995.1985.tb02681.x
  6. Bendtzen K, Mandrup-Poulsen T, Nerup J, Nielsen HJ, Dinarello CA, Svenson M. Cytotoxicity of human pl7 interleukin-1 for pancreatic islets of Langerhans. Science. 1986 ; 232 : 1545-7. https://doi.org/10.1126/science.3086977
  7. Wei Chen, KonstantinV. Salojin, Qing-sheng Mi, Marsha Grattan, T Craig Meagher, Peter Zucker and Terry L Delovitch. Insulin-like growth factor (IGF)-I/IGF-binding protein-3 complex : therapeutic efficacy and mechanism of protection against type 1 diabetes. Endocrinology. 2003.
  8. 서부일, 최호영. 임상한방본초학. 서울 : 영림사. 2004 : 126-9.
  9. 김호철. 한약약리학. 파주 : 집문당. 2001 : 66-7.
  10. 著者 未詳. 神農本草經. 台北 : 文光圖書有限公司. 1982 : 91.
  11. 章永紅 編著. 抗癌中藥大全. 南京 : 江蘇科學技術出版社. 2000 : 341.
  12. 최유행, 김갑성, 이승덕. 桂枝藥鍼刺戟이 mouse의 LPS 유발 관절염 중 세포면역성반응에 미치는 영향. 대한침구학회지. 2001 ; 18(1) : 100-12.
  13. 박종은, 최혁재, 정석희, 김남재, 김동현. 빈용한약재의 진통 소염활성. 생약학회지. 2001 ; 32(4) : 257-68.
  14. 박명준, 박용기. 계피나무의 부위별 抗酸化 作用에 관한 연구(I). 대한본초학회지. 2000 ; 15(2) : 45-55.
  15. Mang B, Wolters M, Schmitt B, Kelb K, Lichinghagen R, Stichtenoth DO, Hahn A. Effects of a cinnamon extract on plasmaglucose, HbA1c, and serum lipid in diabetes mellitus type 2. Eur J Clin Invest. 2006 ; 36 : 340-4. https://doi.org/10.1111/j.1365-2362.2006.01629.x
  16. Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003 ; 26(12) : 3215-8. https://doi.org/10.2337/diacare.26.12.3215
  17. Paul Crawford. Effectiveness of Cinnamon for Lowering Hemoglobin A1C in Patients with Type 2 Diabetes : A Randomized, Controlled Trial. JABFM. 2009 ; 22 (5) : 507-12. https://doi.org/10.3122/jabfm.2009.05.080093
  18. Kim SH, Hyun SH, Choung SY. Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice. J Ethnopharmacol. 2006 ; 104(1-2) : 119-23. https://doi.org/10.1016/j.jep.2005.08.059
  19. Dugoua JJ, Seely D, Perri D, Cooley K, Forelli T, Mills E, Koren G. From type 2 diabetes to antioxidant activity : a systematicreview of the safety and efficacy of common and cassia cinnamon bark. Can J Physiol Pharmacol. 2007 ; 85(9) : 837-47. https://doi.org/10.1139/Y07-080
  20. Yin CS, Jeong HS, Park HJ, Baik YS, Yoon MH, Choi CB, Koh HK. A proposed transpositional acupoint system in a mouse and rat model. Research in Veterinary Science. 2008 ; 84 : 159-5. https://doi.org/10.1016/j.rvsc.2007.04.004
  21. Muniappan L, Leelavinothan P, Sandhya S, Ramesh B. Insulin-secretagogue activity and cytoprotective role of the traditional antidiabetic plant Scoparia dulcis(sweet broomweed). Life Sciences. 2004 ; 75 : 2003-14. https://doi.org/10.1016/j.lfs.2004.05.012
  22. Todd JA, Bell JI, McDevitt HO. HLA-$DQ{\beta}$ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987 ; 329 : 599-604. https://doi.org/10.1038/329599a0
  23. Yoon JW. Role of viruses and environmental factors in induction of diabetes. Curr Top Microbiol Immunol. 1990 ; 4 : 95-123.
  24. Vinik A, Pittenger G, Rafaeloff R, Rosenberg L, Duguid W. Determinants of pancreatic islet cell mass : a balance between neogenesis and senescense/apoptosis. Diabetes Rev. 1996 ; 4 : 235-63.
  25. Gepts W, Lecompte PM. The pancreatic isletsin diabetes. Am J Med. 1980 ; 70 : 105-15.
  26. O'Brien BA, Harmon BV, Cameron DP, Allan DJ. Apoptosis is the mode of $\beta$ cell death responsible for the development of IDDM in the NOD mouse. Diabetes. 1997 ; 46 : 750-7. https://doi.org/10.2337/diabetes.46.5.750
  27. O'Brien BA, Harmon BV, Cameron DP, Allan DJ. Beta cell apoptosis is responsible for the development of IDDM in the multiple low dose streptozotocin model. J Patho. 1996. 178 ; 176-81. https://doi.org/10.1002/(SICI)1096-9896(199602)178:2<176::AID-PATH433>3.0.CO;2-8
  28. Kurrer MO, Pakala SV, Hanson HL, Katz JD. $\beta$ cell apoptosis in T cell-mediated autoimmune diabetes. Proc Natl Acad Sci. 1997 ; 94 : 213-8. https://doi.org/10.1073/pnas.94.1.213
  29. 박히준, 이지숙, 이재동, 김남재, 표지희, 강전모, 최일환, 김수영, 심범상, 이제현, 임사비나. 계지의 항염 효과에 관한 연구. 대한한의학회지. 2005 ; 26(2) : 140-51.
  30. 김성준, 박성민, 강희, 심범상, 김성훈, 최승훈, 안규석. 桂枝의 collagen 유발 관절염에 대한 소염 효과-DBA/1J mouse에서의 병태 관찰 및 RAW 264.7에서의 cytokine 분비 측정-. 동의생리병리학회지. 2008 ; 22(3) : 542-7.
  31. Herr RR, Eble TE, Berby ME, Jahnke HK. Isolation and characterization of streptozotocin. Antibiol Annu. 1959 : 236.
  32. Rakieten N, Rakieten ML, Nadkarni MV. Studies on the diabetogenic actions of streptozotocin. Cancer Chemother Rep. 1963 ; 29 : 91.
  33. Evans JS, Gerritsen GC, Mann KM, Owen SP. Antitumor and hyperglycemic activity of streptozotocin and its cofactor. Cancer Chemother Rep. 1965 ; 48 : 1.
  34. Arison RN, Feudale EL. Induction of renaltumor by streptozotocin in rats. Nature. 1967 ; 214 : 1254. https://doi.org/10.1038/2141254a0
  35. Baeuerle PA. $I{\kappa}B-NF-{\kappa}B$ structure : at the interface of inflammation control. Cell. 1988 ; 95 ; 729-31. https://doi.org/10.1016/S0092-8674(00)81694-3
  36. Morise Z, Komatsu S, Fuseler JW, Granger DN, Perry M, Issekuts AC, Grisham MB. ICAM-1 and P-selectin expression in a model of NSID-induced gastropathy. Am J Physio. 1998 ; 27 : 246-52.
  37. Li YX, Li N, Li YS, Wu B, Li JS. Upregulated intragraft gene expression, ICAM-1 and IL-2R molecules, and apoptotic epithelial cells during rejection of rat small intestine allografts. Transplant Proceed. 2000 ; 32 : 1283-6. https://doi.org/10.1016/S0041-1345(00)01227-6
  38. Groszmann RJ. Hyperdynamic state in chronic liver diseases. J Hepatol. 1993; 17(2) : 38-40. https://doi.org/10.1016/S0168-8278(05)80454-4
  39. Tamura S, Hanada M, Ohnishi M, Katsura K, Sasaki M, Kobayashi T. Regulation of stress-activated protein kinase signaling pathways by protein phosphatases. Eur J Biochem. 2002 ; 269 : 1060-6. https://doi.org/10.1046/j.0014-2956.2002.02754.x
  40. Hofmann TG, Stollberg N, Schmitz ML, Will H. HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells. Cancer Res. 2003 ; 63 : 8271-7.
  41. Chun JS. Expressin, activity, and regulation of MAP kinases in cultured chondrocytes. Medhtods Mol Med. 2004 ; 100L 291-306.
  42. Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation on mammalian cells. Cell research. 2002 ; 12 : 9-18. https://doi.org/10.1038/sj.cr.7290105