A Study on the Effects to Diabetic Nephropathy of Hachimi-jio-gan in RatsYokozawa T.a · Yamabe N.a · Cho E.J.a · Nakagawa T.a · Oowada S.b
aInstitute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama and bFirst Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
To investigate the effects of Hachimi-jio-gan on diabetic nephropathy, we employed an animal model, rats subjected to sub-total nephrectomy followed by streptozotocin injection, and administered Hachimi-jio-gan orally at a dose of 50, 100 or 200 mg/kg body weight/day for 15 weeks. The administration of Hachimi-jio-gan reduced dose-dependently the elevated blood glucose and urinary protein excretion levels in rats with diabetic nephropathy over the experimental period, whereas it increased creatinine clearance significantly, suggesting that Hachimi-jio-gan would prevent or delay the progression of diabetic nephropathy. In addition, the serum glycosylated protein and urea nitrogen levels were markedly elevated in rats with diabetic nephropathy compared with normal rats, and were significantly reduced by the administration of Hachimi-jio-gan, whereas Hachimi-jio-gan reversed the decrease in the serum albumin level. The serum triglyceride and total cholesterol concentrations were reduced by Hachimi-jio-gan, implying that Hachimi-jio-gan would improve the metabolic disorder of lipids caused by diabetic nephropathy. Moreover, Hachimi-jio-gan inhibited lipid peroxidation in the serum and kidney, which suggests that Hachimi-jio-gan would ameliorate oxidative stress associated with diabetic nephropathy. Furthermore, the disorders of the glucose-dependent metabolic pathway due to this pathological condition were also normalized by the administration of Hachimi-jio-gan through decreases in advanced glycation end-product formation and sorbitol levels in the kidney. Hachimi-jio-gan protected against the development of renal lesions, glomerular sclerosis, tubulointerstitial lesions, mesangial matrix expansion and arteriolar sclerosis, estimated by histopathological evaluation and scoring. This study suggests that Hachimi-jio-gan may be a novel therapeutic approach to improving diabetic nephropathy.
© 2004 S. Karger AG, Basel
Friedman EA: Diabetic renal disease; in Ellenberg M, Rifkin H (eds): Diabetes mellitus: Theory and Practice. New York, Medical Examination Publishing, 1983, pp 759–776.
- Selb JV, FitzSimmons SC, Newman JM, Katz PP, Sepe S, Showstack J: The natural history and epidemiology of diabetic nephropathy. Implications for prevention and control. JAMA 1990;263:1954–1960.
Held PJ, Port FK, Webb RL, Wolfe RA, Garcia JR, Blagg CR, Agodoa LY: The United States Renal Data System’s 1991 annual data report: An introduction. Am J Kidney Dis 1991;18:1–16.
Parving HH, Andersen AR, Smidt UM, Svendsen PA: Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1983;28:1175–1179.
- Lewis EJ, Hunsicker LG, Bain RP, Rohde RD: The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456–1462.
Preston RA: Renoprotective effects of antihypertensive drugs. Am J Hypertens 1999;12:S19–S32.
- Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861–869.
- Goto M, Inoue H, Seyama Y, Yamashita S, Inoue O, Yumioka E: Comparative effects of traditional Chinese medicines (dai-saiko-to, hatimi-zio-gan and byakko-ka-ninzin-to) on experimental diabetes and hyperlipidemia. Nippon Yakurigaku Zasshi 1989;93:179–186.
Furuya Y, Kawakita T, Tajima S: Effect of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on insulin resistance in non-insulin-dependent diabetes mellitus model mice. J Trad Med 1999;16:123–128.
Yamada T: Kinki Youryaku. Tokyo, Kyouwa-Kikaku, 1992, pp 1–7.
Huang T: A Handbook of Traditional Chinese Prescriptions of Dubious and Complicated Cases. Beijing, China Medical and Pharmaceutical Science and Technology Publishing House, 1997, pp 527–538.
Nakagawa T, Yokozawa T, Terasawa K: A study of Kampo medicines in a diabetic nephropathy model. J Trad Med 2001;18:161–168.
- Yokozawa T, Nakagawa T, Wakaki K, Koizumi F: Animal model of diabetic nephropathy. Exp Toxic Pathol 2001;53:359–363.
- McFarland KF, Catalano EW, Day JF, Thorpe SR, Baynes JW: Nonenzymatic glycosylation of serum proteins in diabetes mellitus. Diabetes 1979;28:1011–1014.
Naito C, Yamanaka T: Lipid peroxides in atherosclerotic diseases. Jpn J Geriat 1978;15:187–191.
Sakagishi Y: Total protein; in Saito M, Kitamura M, Niwa M (eds): Rinsho Kagaku Bunseki II. Tokyo, Tokyo Kagaku Dojin, 1968, pp 115–142.
- Nakayama H, Mitsuhashi T, Kuwajima S, Aoki S, Kuroda Y, Itoh T, Nakagawa S: Immunochemical detection of advanced glycation end products in lens crystallins from streptozotocin-induced diabetic rat. Diabetes 1993;42:345–350.
- Shinohara R, Mano T, Nagasaka A, Sawai Y, Uchimura K, Hayashi R, Hayakawa N, Nagata M, Makino M, Kakizawa H, Itoh Y, Nakai A, Itoh M: Effects of thyroid hormone on the sorbitol pathway in streptozotocin-induced diabetic rats. Biochim Biophys Acta 1998;1425:577–586.
- Mihara M, Uchiyama M: Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271–278.
- Itzhaki RF, Gill DM: A micro-biuret method for estimating proteins. Anal Biochem 1964;9:401–410.
- Bell DS: Diabetic nephropathy: Changing concepts of pathogenesis and treatment. Am J Med Sci 1991;301:195–200.
- Brownlee M, Vlassara H, Cerami A: Non-enzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med 1984;101:527–537.
- Larkins RG, Dunlop ME: The link between hyperglycaemia and diabetic nephropathy. Diabetologia 1992;35:499–504.
Alaveras AE, Thomas SM, Sagriotis A, Viberti GC: Promoters of progression of diabetic nephropathy: The relative roles of blood glucose and blood pressure control. Nephrol Dial Transplant 1997;12(suppl 2):71–74.
Cooper ME, Gilbert RE, Epstein M: Pathophysiology of diabetic nephropathy. Metabolism 1998;47(suppl 1):3–6.
- Derubertis FR, Craven PA: Activation of protein kinase C in glomerular cells in diabetes. Mechanisms and potential links to the pathogenesis of diabetic glomerulopathy. Diabetes 1994;43:1–8.
Fumo P, Kuncio GS, Ziyadeh FN: PKC and high glucose stimulate collagen α1 (IV) transcriptional activity in a reporter mesangial cell line. Am J Physiol 1994;267:F632–F638.
- Cooper ME: Pathogenesis, prevention and treatment of diabetic nephropathy. Lancet 1998;352:213–219.
- Reddi AS, Camerini-Davalos RA: Diabetic nephropathy. An update. Arch Intern Med 1990;150:31–43.
Luo WQ, Kanno T, Winarto A, Iwanaga T, Jun L, Futai Y, Yanaihara C, Yanaihara N: An experimental analysis of therapeutic effects of a Chinese herbal prescription in streptozotocin-treated rats. Biomed Res 1998;19:127–133.
Nagoyashi S, Nishiura T, Hagiwara Y: Effect of Hachimijio-to on the alloxan diabetes. J Jpn Soc Orient Med 1966;17:236–239.
Yoshida H: Effect of Ba-wei-wan (Hachimi-gan), one of the most common traditional Chinese recipes on diabetic neuropathy. J Jpn Soc Orient Med 1979;29:175–182.
- Yabe-Nishimura C: Aldose reductase in glucose toxicity: A potential target for the prevention of diabetic complications. Pharmacol Rev 1998;50:21–33.
- Vlassara H, Striker LJ, Teichberg S, Fuh H, Li YM, Steffes M: Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats. Proc Natl Acad Sci USA 1994;91:11704–11708.
- Niwa T: β2-Microglobulin dialysis amyloid and its formation: Role of 3-deoxyglucosone and advanced glycation end products. Nephron 1997;76:373–391.
- Raj DSC, Choudhury D, Welbourne TC, Levi M: Advanced glycation end products: A neurologist’s perspective. Am J Kidney Dis 2000;35:365–380.
- Goldfarb S, Ziyadeh FN, Kern EF, Simmons DA: Effects of polyol-pathway inhibition and dietary myo-inositol on glomerular hemodynamic function in experimental diabetes mellitus in rats. Diabetes 1991;40:465–471.
- Hamada Y, Araki N, Koh N, Nakamura J, Horiuchi S, Hotta N: Rapid formation of advanced glycation end products by intermediate metabolites of glycolytic pathway and polyol pathway. Biochem Biophys Res Commun 1996;228:539–543.
- Saito T: Abnormal lipid metabolism and renal disorders. Tohoku J Exp Med 1997;181:321–337.
- Mulec H, Johnsen SA, Wiklund O, Bjorck S: Cholesterol: A renal risk factor in diabetic nephropathy? Am J Kidney Dis 1993;22:196–201.
- Kramer-Guth A, Quaschning T, Greiber S, Wanner C: Potential role of lipids in the progression of diabetic nephropathy. Clin Nephrol 1996;46:262–265.
Haranaka R, Mochizuki N, Watabe S, Ohwada S, Kosoto H, Kakemura H, Kuwabara Y, Hirose N, Hasegawa R, Kobayashi M: Studies of Ba-wei-wan. I. Lipid and carbohydrate metabolism in aged rat and mice. Proc Symp Wakan-Yaku 1982;15:15–20.
Mochizuki N, Haranaka R, Watabe S, Ohwada S, Kosato H, Takemura H, Takanashi K, Hyon CS, Hasegawa R, Kobayashi M: Studies of Ba-wei-wan. II. Cholesterol metabolism in aged rats and mice using 1,2-3H cholesterol and 4- 14C cholesterol. Proc Symp Wakan-Yaku 1982;15:21–25.
- Kimura Y, Okuda H, Arichi S: Effects of Japanese and Chinese traditional medicine ‘hachimi-gan’ (‘ba-wei-wan’) on lipid metabolism in rats fed high sugar diet. Planta Med 1987;53:128–131.
- Giugliano D, Ceriello A, Paolisso G: Oxidative stress and diabetic vascular complications. Diabetes Care 1996;19:257–267.
- Salahudeen AK, Kanji V, Reckelhoff JF, Schmidt AM: Pathogenesis of diabetic nephropathy: A radical approach. Nephrol Dial Transplant 1997;12:664–668.
- Winetz JA, Golbetz HV, Spencer RJ, Lee JA, Myers BD: Glomerular function in advanced human diabetic nephropathy. Kidney Int 1982;21:750–756.
Adler S: Structure-function relationships in diabetic nephropathy: Lessons and limitations. Kidney Int 1997;52:S42–S45.
- Yaqoob M, McClelland P, Patrick AW, Stevenson A, Mason H, White MC, Bell GM: Evidence of oxidant injury and tubular damage in early diabetic nephropathy. QJM 1994;87:601–607.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.