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Renoprotective Effects of Korean Red Ginseng

고려홍삼의 당뇨병성 신장병증 개선 효과

  • 김영림 (경희대학교 약학대학 약물학교실) ;
  • 정성현 (경희대학교 약학대학 약물학교실)
  • Published : 2004.06.01

Abstract

The renoprotective effects of Korean Red Ginseng were examined in STZ-induced diabetic spontaneously hypertensive rats (SHR). After 3 day administration of streptozotocin (STZ), animals were divided into four groups : Group 1, hypertensive rats (H); Group 2, hypertensive rats with diabetes (HD); Group 3, hypertensive rats with diabetes administered with 100 mg/kg of ginseng total saponin(GTS); Group 4, hypertensive rats with diabetes administered with 600 mg/kg of ginseng non-saponin (GNS). After 2 weeks oral administraions of GTS and GNS, body weight, kidney weight, plasma glucose, urinary albumin excretion, serum creatinine, urea nitrogen and blood pressure were examined. After 3,7 and 21 day of STZ administration, expressions of TGF-${\beta}$1 and fibronectin in kidney were analyzed by immunoblotting and/or immunohistochemistry. GTS and GNS treatments slightly decreased blood pressure when compared to H and HD groups. Also, GTS and GNS treatments ameliorated kidney hypertrophy without affecting plasma glucose levels. Meanwhile, GNS treatment increased Cu/Zn-SOD activity in kidney and generally showed more efficient renoprotective effects than GTS. We suggest that the renoprotective effects of ginseng partially result from downregulations of TGF-${\beta}$1, fibronectin expressions and anti-oxidative activity of ginseng non-saponin.

자연발생적 고혈압 흰쥐에 STZ로 당뇨를 유발한 고혈압-당뇨 질환모델에서 고려홍삼 조사포닌분획과 비사포닌 분획간의 신장보호 활성을 비교해 보았다. STA 65mg/kg용량을 투여한 후 3일에 네 그룹으로 나누어 본 실험에 임하였다. 신장비대에 대한 저해 활성을 비교해 보았을 때 GTS와 GNS 각각 12, 13% 억제 활성을 나타내었고 두 군간에는 유의적인 차이를 보이지 않았다. 한편 요 중 요소질소의 배설은 GNS 투여군에서는 69% 증가(p<0.05)한 반면 GTS 투여군은 31%만이 증가하였다. 혈중 포도당, 콩 콜레스테롤 및 중성지방의 경우는 고혈압-당뇨 대조군과 비교시 홍삼투여군 두군 모두에서 유의한 차이를 발견할 수 없었다. 반면 oxidative stress를 저해하는 효소인 SOD 활성에 있어서는 GNS투여군에서 대조군에 비해 17%유의하게 상승하는 활성을 보여주었다. 신장비대의 지표인 TGG-$\beta$1, fibronectin그리고 upstream의 MEPK인 p-38, ERK 등의 발현을 그룹간 비교해 본 결과 모든 지표에서 비사포닌 분획이 사포닌 분획에 비해 우수한 억제활성을 나타내었다. TGF-$\beta$1의 mRNA 및 단백질의 발현을 살펴보았을 때 GNS 투여군은 각각 33%, 91% 억제활성을 나타낸 반면 GTS 투여군은 각각 5%, 65% 억제활성을 나타내었다. Fibronectin 단백질의 발현에서도 GNS 투여군은 87% 억제 활성을 나타낸 반면 GTS 투여군은 28% 저해활성을 나타내었다. 본 실험의 결과를 종합해보면 고려홍삼의 신장보호 활성은 사포닌 분획보다는 비사포닌 분획에 함유된 성분에 의해 일어나는 효과가 아닌가 추측된다.

Keywords

References

  1. Sonnenborn, U. and Proppert, Y. : Ginseng (Panax ginseng C.A. Meyer). Zeitschrift fur Phytotherapie 11, 35-49 (1990)
  2. Han, K.H., Choe, S.C., Kim, H.S., Shou, D.W., Nam, K.Y., Oh, B.H., Lee, M.M., Park, Y.B., Choi, Y.S., Seo, J.D. and Lee, Y.W. : Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hyper-tension. Am. J. Chi. Med. 26, 199-209 (1998) https://doi.org/10.1142/S0192415X98000257
  3. Sotaniemi, E.A., Haapakoski, E. and Rautio, A. : ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care 18(10), 1373-1375 (1995) https://doi.org/10.2337/diacare.18.10.1373
  4. Anoja, S., Attle, J.A W. and Yuan, C.S. : Ginseng pharmacology. Biochemical Pharmacology 58, 1685-1693 (1999) https://doi.org/10.1016/S0006-2952(99)00212-9
  5. Park, H.J., Rhee, M.H., Park, K.M., Nam, K.Y. and Park, K.H. : Effect of non-saponin fraction from Panax ginseng on cGMP and thromboxane $A_2$ in human platelet aggregation. Journal of Ethnopharmacology 49, 157-162 (1995) https://doi.org/10.1016/0378-8741(95)01317-2
  6. Kim, Y.H., Park, K.H. and Rho, H.M. : Transcriptional activation of the Cu,Zn superoxide dismutase gene through the AP2 site by ginsenoside $Rb_2$ extrated from a medicinal plant, Panax ginseng. The Journal of Biochemical Chemistry 271(40), 24539-24534 (1996)
  7. Chang, M.S., Lee, S.G. and Rho, H.M. : Transcriptional activation of Cu/Zn superoxide dismutase and catalase genes by panaxadiol ginsenosides extracted from panx ginseng. Phytotherapy Research 13, 641-644 (1999) https://doi.org/10.1002/(SICI)1099-1573(199912)13:8<641::AID-PTR527>3.0.CO;2-Z
  8. 주충노, 김주현 : 인삼 saponin 분획의 고혈당 강하작용에 관한 연구(1). Korean J. Ginseng Sci. 16(3), 190-197 (1992)
  9. 주충노, 윤수희, 이향숙, 김용덕, 이희봉, 구자현 : saponin (2). Korean J. Ginseng Sci. 16(3), 198-209 (1992)
  10. Yokozawa, T., Zhou, J., Hattori, M., Inaba, S., Okada, T. and Oura, H. : Effects of ginseng in nephrectomized rats. Biol. Pharm. Bull. 17(11), 1485-1489 (1994) https://doi.org/10.1248/bpb.17.1485
  11. Hattori, T., Fujitsuka, N., Kurogi, A. and Shindo, S. : Effect of Onpi-to (TJ-8117) on TGF-beta 1 in rat with 5/6 nephrectomized chronic renal failure. Nippin Jinzo Gakkai Shi 38(11), 475-483 (1996)
  12. Zhang, Y. : Protective effects of ginsenosides on warm ischemic damages of the rabbit kidney. Zhonghua Yi Xue Za Zhi 72(2), 84-85 (1992)
  13. Han, S. W. and Kim, H. : Ginsenosides stimulate endogeous production of nitric oxide in rat kidney. Int. J. Biochem. Cell. Biol. 28(5), 573-580 (1996) https://doi.org/10.1016/1357-2725(95)00163-8
  14. Trinder, T. : Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Annal. Clin. Biochem. 6, 24-28 (1969) https://doi.org/10.1177/000456326900600108
  15. Lowry, O.H., Rosebrough, W.I., Farr, A.L. and Randal, R.J. : Protein measurement with the Folin phenol reagnet. J. Biol. Chem. 193, 265-275 (1951)
  16. Kaneko, S., Takizawa, H., Takeda, M., Shou, I. and Tomino, Y. : Effects of the antihypertensive drug nifedipine on albuminuria and renal histopathology in young spontaneously hypertensive rats with diabetes. General pharmacology 33, 363-367 (1999) https://doi.org/10.1016/S0306-3623(98)00254-7
  17. Alluru, S., Reddi, V. R., Nimmagadda, A. L., Kuo, H.R. and Bollineni, J.S. : Effect of antihypertensive therapy on renal injury in type 2 diabetic rats with hypertension. Hypertension 36, 233-238 (2000) https://doi.org/10.1161/01.HYP.36.2.233
  18. Srinivasan, P. S., Hakim, Z. S., Santani, D. D. and Goyal, R. K. : Effects of chronic treatment with amlodipine in streptozotocin diabetic and spontaneously hypertensive rats. Pharmacological Research 35(5), 423-428 (1997) https://doi.org/10.1006/phrs.1997.0154
  19. Koya, D. and King, G.L. : Protein kinase C activation and the development of diabetic complication, Diabetes 47, 859-866 (1998) https://doi.org/10.2337/diabetes.47.6.859
  20. Isshiki, K., Haneda, M., Koya, D., Maeda, S., Sugimoto, T. and Kikkawa, R. : Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats. Diabetes 49, 1022-1032 (2000) https://doi.org/10.2337/diabetes.49.6.1022
  21. Sharma, K. and Ziyadeh, F.N. : Hyperglycemia and diabetic kidney disease : The case for transforming growth factor-1a as a key mediator. Diabetes 44, 1139-1146 (1995) https://doi.org/10.2337/diabetes.44.10.1139
  22. Koli, K., Saharinen, J., Hyytiainen, M., Penttinen, C. and Keski-oja, J. : Latency, activation and binding proteins of TFG-1a. Micros. Res. Tech. 52, 354-362 (2001) https://doi.org/10.1002/1097-0029(20010215)52:4<354::AID-JEMT1020>3.0.CO;2-G
  23. Awazu, M., Ishikura, K., Hida, M. and Hoshiya, M. : Mechanisms of mitogen-activated protein kinase activation in experimental diabetes. J. Am. Soc. Nephrol. 10, 738-745 (1999)
  24. Isono, M., Iglesia-de la Cruz, M.C., Chen, S., Hong, S.W. and Ziyadeh, F.N. : Extracellular signal-regulated kinase mediates stimulation of TGF-a1 and matrix by high glucose in mesangial cell. J. Am. Soc. Nephrol. 11, 2222-2230 (2000)

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