Poria cocos Herbal Acupuncture Prevents ${\beta}$-cell Damage on Streptozotocin-induced Diabetic Rat

Streptozotocin 유도 당뇨 흰쥐에서 복령약침의 ${\beta}$-cell 손상 방지 효과

  • Seo, Chang-Wan (Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Seo, Byung-Kwan (Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Kim, Jong-In (Korea Institute of Oriental Medicine) ;
  • Kang, Sung-Keel (Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University)
  • 서창완 (경희대학교 한의과대학 침구학교실) ;
  • 서병관 (경희대학교 한의과대학 침구학교실) ;
  • 김종인 (한국한의학연구원) ;
  • 강성길 (경희대학교 한의과대학 침구학교실)
  • Published : 2009.10.20

Abstract

목적 : 정상 췌장조직 속에 존재하는 췌장 소도세포들을 파괴시켜 고혈당을 유발시키고 복령 물추출물로 약침을 시술하여 췌장 조직의 보호효과와 항당뇨 효과를 살펴보고자 실험을 진행하였다. 방법 : 5주령의 Sprague-Dawley rat을 통제된 실험실 환경에 적응시킨 후 1주일간 복령약침액(125mg/kg 복령약침군 및 250mg/kg 복령약침군)을 좌우 신수($BL_{23}$)에 교대로 각각 피하에 약침하고 streptozotocin을 복강내 주사하여 3일 후 diabetes mellitus 유도 정도를 평가하고 2주일간 추가 치료를 진행 한 뒤, 혈액지표(plasma glucose, insulin, TG, TC, NEFA, sGOT, sGPT, ALP, BUN, CRE)와 췌장조직의 형태학적 분석 및 염증 관련 단백질의 발현을 평가하였다. 결과 : 복령약침군(125mg/kg 복령약침군 및 250mg/kg 복령약침군)에서 insulin과 triglyceride, NEFA 수치가 유의하게 감소하였으며 간 기능 효소수치인 sGOT가 감소하는 경향을 나타내었으나, 신장기능지수는 유의한 감소를 나타내지 않았다. 특히 250mg/kg 복령약침군에서 streptozotocin 투여로 인한 pancreatic islet의 형태학적 변성이 현저하게 개선되었다. Western blot 결과 JNK-2, P-JNK-2, P-JNK-1, ERK1/2 및 phosphorylated ERK1의 발현이 감소되었다. 결론 : 복령약침이 고인슐린혈증과 고지질질혈증을 개선시키고 streptozotocin에 의한 pancreatic islet의 파괴를 억제하며, 이는 inflammation-related transcription factor인 NF-kB와도 관련이 있는 것으로 판단된다. 향후 복령약침의 항당뇨 효과와 그 기전에 관한 추가 연구가 필요할 것으로 사료된다

Keywords

References

  1. The expert committee on the diagnosis and classification of diabetes mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003 ; 26 : s5-s20. https://doi.org/10.2337/diacare.26.2007.S5
  2. Atkinson MA, Maclaren NK. The pathogenesis of insulin dependent diabetes. N Engl J Med. 1994 ; 331 : 1428-36. https://doi.org/10.1056/NEJM199411243312107
  3. Foulis AK, McGill M, Farquaharson MA. Insulin in type I (insulin-dependent) diabetes mellitus in man-macrophages, lymphocytes, and interferongamma containing cells. J Pathol. 1991 ; 165 : 97-103. https://doi.org/10.1002/path.1711650203
  4. HE Hohmeier, VV Tran, G Chen, R Gasa, CB Newgard. Inflammatory mechanisms in diabetes : lessons from the ${\beta}$-cell. International Journal of Obesity. 2003 ; 27 : s12-s16.
  5. Francoise Homo-Delarche, Hemmo AD Rexhage. Immune cells, pancreas development, regeneration and type 1 diabetes. Trends in immunology. 2004 ; 25(5) : 222-9. https://doi.org/10.1016/j.it.2004.02.012
  6. Department of herbology. Herbology. 4th edition. Seoul : Younglimsa. 1998 : 302-4.
  7. Han Duckyong, Modern Pharmacognosy. Seoul : Hakchangsa. 1989 : 214.
  8. Otsuka H, Fujioka S, Kimiya T, Mizuta E and TAkarmto M. Studies on anti-inflammatory agents. VI, Anti-inflammatory constituents of Cinnamomum sieboldii Meissn. Yakugaku-zasshi, 1982 : 102, 162.
  9. Han DS. Pharmacognosy. Seoul : Dongmyungsa. 1988 : 110, 116, 156, 159, 229, 174, 283, 356.
  10. Wei Chen, Konstantin V 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 type1 diabetes. Endo crinology. 2003.
  11. Kaminaga T, Yasukawa K, Kanno H, Tai T, Nunoura Y, Takido M. Inhibitory effects of lanostane-type triterpene acids, the compo nents of Poria cocos, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two stage carcinogenesis in mouse skin. Oncology. 1996 ; 53 : 382-5. https://doi.org/10.1159/000227592
  12. Kloppel G, Lohr M, Habich K, Oberholzer M, Heitz PU. Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. Surv Synth Pathol Res. 1985 ; 4 : 110-25.
  13. Zimmet PZ, Tuomi T, Mackay R, Rowley MJ, Knowles W, Cohen M, Lang DA. Latent autoimmune diabetes mellitus in adults (LADA) : the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med. 1994 ; 11 : 299-303. https://doi.org/10.1111/j.1464-5491.1994.tb00275.x
  14. Cantor AB, Krischer JP, Cuthbertson DD, Schatz DA, Riley WJ, Malone J, Schwartz S, Quattrin T, Maclaren NK. Age and family relationship accentuate the risk of IDDM in relatives of patients with insulin dependent diabetes. J Clin Endocrinol Metab. 1995 ; 80 : 3739-43. https://doi.org/10.1210/jc.80.12.3739
  15. Eizirik DL, Mandrup-Poulsen T. A choice of death: the signal-transduction of immune-mediated-cell apoptosis. Diabetologia. 2001 ; 44 : 2115-33. https://doi.org/10.1007/s001250100021
  16. Miriam Cnop, Nils Welsh, Jean-Christophe Jonas, Anne Jorns, Sigurd Lenzen, Decio L Eizirik. Mechanisms of pancreatic ${\beta}$-cell death in type 1 and type 2 diabetes. Diatetes. 2005 ; 54 : s97-s107.
  17. Vavra JJ, Deboer C, Dietz A, Hanka LJ, Sokolski WT. Streptozotocin, a new antibacterial antibiotic. Antibiot Annu. 1959 ; 7 : 230-5.
  18. Mansford KR, Opie L. Comparison of metabolic abnormalities in diabetes mellitus induced by streptozotocin or by alloxan. Lancet. 1968 ; 1 : 670-1.
  19. Brentjens R, Saltz L. Islet cell tumors of the pancreas : the medical oncologist's perspective. Surg Clin North Am. 2001 ; 81 : 527-42. https://doi.org/10.1016/S0039-6109(05)70141-9
  20. Katsumata K, Katsumata K Jr, Katsumata Y. Protective effect of diltiazem hydro chloride on the occurrence of alloxan-or streptozotocin-induced diabetes in rats. Horm MetabRes. 1992 ; 24 : 508-10. https://doi.org/10.1055/s-2007-1003376
  21. Turk J, Corbett JA, Ramanadham S, Bohrer A, Mcdaniel ML. Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochem Biophys Res Commun. 1993 ; 197 : 1458-64. https://doi.org/10.1006/bbrc.1993.2641
  22. Shalini Pathak, Helge C Dorfmueller, Vladimir S Borodkin and Daan MF van Aalten. Chemical Dissection of the Link between Streptozotocin, OGlcNAc, and Pancreatic Cell Death. Chem Biol. 2008 ; 15(8) : 799-807. https://doi.org/10.1016/j.chembiol.2008.06.010
  23. T Szkudelski. The Mechanism of alloxan and streptozotocin action in b cells of the rat pancreas. Physiol. Res. 2001 ; 50 : 536-46.
  24. Cao Shao Ming. Comparison of acupuncture, moxibustion, warming. acupuncture therapy on diabetes mellitus. Zhongguo Zhenjiu. 1997 ; 17(10) : 586.
  25. Mang B, Wolters M, Schmitt B, Kelb K, Lichtinghagen R, Stichtenoth DO, Hahn A. Effects of a cinnamon extract on plasma glucose, 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
  26. 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
  27. Hye Jung Lee, Yong Tae Choi. (A)Study of ginseng radix aqua-acupuncture on the allo xan-induced diabetic rabbits and retrograde transport of horseradish peroxidase. Journal of college of Oriental medicine, Kyunghee university. 1987 ; 10 : 169-87.
  28. Jang Jae Lee. The effect of Lycii Radicis Cortex Hexane herbal acupuncture on analgesia and blood glucose. Journal of college of Daejeon university. 1997.
  29. Luo Su Sheng et al. The effect of Acanthopanacis Cortex intravenous herbal acupuncture on intradermal cell count in plasma and urine in diabetes mellitus. Journal of Integrated Traditional and Western Medicine. 2001 ; 21(2) : 105-7.
  30. Liu Zhi Oiang et al. The effect of Astragali Radix intravenous herbal acupuncture on platelet in diabetes mellitus. Journal of Integrated Traditional and Western Medicine. 2001 ; 21(4) : 274-6.
  31. Lam Hoang, Soon-ho Kwon, Kyung-ah Kim, Jong-moon Hur, Young-hwa Kang, Kyung-sik Song. Chemical standardization of Poria cocos. Kor J Pharmacogn. 2005 ; 36(3) : 177-85.
  32. Sato M, Tai T, Nunoura Y, Yajima Y, Kawashima S, Tanaka K. Dehydrotramete nolic acid induces preadipocyte differentiation and sensitizes animal models of non insulindependent diabetes mellitus to insulin. Biol Pharm Bull. 2002 Jan ; 25(1) : 81-6. https://doi.org/10.1248/bpb.25.81
  33. Son youngjong, Lee youngjong. The effects of Sinomenii caulis and Hoelen on the levels of blood glucose in rats. Kor J Herbology. 2003 ; 18(1) : 65-71.