Download PDF
Horm Metab Res 2001; 33(12): 727-732
DOI: 10.1055/s-2001-19138
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Metformin-Like Effects of Quei Fu Di Huang Wan, a Chinese Herbal Mixture, on Streptozotocin-Induced Diabetic Rat

J. T. Cheng 1 , I. M. Liu 1 , T. C. Chi 1 , H. C. Su 1 , C. G. Chang 2
  • 1 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, R.O.C.
  • 2 Committee on Chinese Medicine and Pharmacy, Department of Health, Executive Yuan, Taipei, Taiwan, R.O.C.
Further Information

Publication History

Publication Date:
18 December 2001 (online)

Also available at
    Permissions and Reprints

Effect on plasma glucose concentration of Quei Fu Di Huang Wan (Quei Fu DHW), the herbal mixture widely used to treat diabetic disorder in Chinese traditional medicine, was investigated in diabetic rats deficient in insulin. Changes of plasma glucose in streptozotocin-induced diabetic rats (STZ-diabetic rats) receiving repeated oral administration of Quei Fu DHW were determined. Also, the mRNA level (by Northern blotting) and protein level (by Western blotting) of phosphoenolpyruvate carboxykinase (PEPCK) in liver from STZ-diabetic rats were measured to compare differences between groups receiving repeated oral administration of Quei Fu DHW, metformin, and two active herbs (Zou Guei or Fuzei) at effective dosages. In STZ-diabetic rats, acute oral administration of Quei Fu DHW decreased the plasma glucose level significantly in a dose-dependent manner from 5 mg/kg to 26.0 mg/kg. Similar treatment with Quei Fu DHW also brought on a plasma glucose-lowering effect in normal rats, although the effectiveness was not as significant as in STZ-diabetic rats. Repeated oral treatment of Quei Fu DHW at 26 mg/kg every 8 h, three times daily for 3 days, produced a plasma glucose-lowering activity similar to that of metformin-treatment in STZ-diabetic rats. Oral administration of Zou Guei (Cinnamomi Cortex) or Fuzei (Aconiti Tuber), the individual constituent of Quei Fu DHW, at the dose of 50 mg/kg into STZ-diabetic rats for 3 days normalized hyperglycemia. Similar to the repeated treatment with Quei Fu DHW, Fuzei at the effective dose reversed the elevated mRNA and protein levels of PEPCK in liver from STZ-diabetic rats. This is consistent with findings that metformin restored the increased gene expression of PEPCK in liver from STZ-diabetic rats. However, the gene expression of PEPCK in STZ-diabetic rats was not influenced by similar treatment with Zou Guei. The present study found that oral administration of Quei Fu DHW could decrease hepatic gluconeogenesis in a way similar to metformin in lowering plasma glucose in diabetic rats lacking insulin. Thus, this preparation may be a helpful adjuvant for the treatment of diabetic disorders in clinical practice.

Key words:

Chinese Traditional Medicine - Quei Fu Di Huang Wan - Metformin - PEPCK

References

  • 1 Goldstein D A, Massry S G. Diabetic nephropathy: clinical course and effect of hemodialysis.  Nephron. 1978;  20 286-296
    PubMedGoogle Scholar
  • 2 Weidmann P, Boehlen L M, de Courten M. Pathogenesis and treatment of hypertension associated with diabetes mellitus.  Am Heart J. 1993;  125 1498-1513
    CrossrefPubMedGoogle Scholar
  • 3 Kamei A, Hisada T, Iwata S. The evaluation of therapeutic efficacy of hachimi-jio-gan (traditional Chinese medicine) to rat galactosemic cataract.  J Ocul Pharmacol. 1987;  3 239-249
    PubMedGoogle Scholar
  • 4 Suzuki J, Kimura M. Hypoglycemic effects of the blended Chinese traditional medicines in genetically and chemically diabetic mice.  Nippon Yakurigaku Zasshi-Folia Pharmacol Japonica. 1984;  83 1-10
    PubMedGoogle Scholar
  • 5 Cheng J T, Liu I M, Chi T C, Su H C, Chang C G. Stimulation of insulin release in rats by Die-Huang-Wan, a herbal mixture used in Chinese traditional medicine.  J Pharm Pharmacol. 2001;  53 273-276
    CrossrefPubMedGoogle Scholar
  • 6 Cheng J T, Liu I M, Chi T C, Su H C, Chang C G. Increase of insulin sensitivity in diabetic rats by Die-Huang-Wan, the herbal mixture used in Chinese traditional medicine (submitted). 
    Google Scholar
  • 7 Cai J F. Origins of medicine and pharmacy.  State Administration of Traditional Chinese Medicine and Pharmacy (eds.), Advanced textbook on traditional Chinese medicine and pharmacy. 1st ed.  Beijing:; New World Press, 1995: 10-14
    Google Scholar
  • 8 Rouru J, Huupponen R, Pesonen U, Koulu M. Subchronic treatment with metformin produces anorectic effect and reduces hyperinsulinemia in genetically obese Zucker rats.  Life Sci. 1992;  50 1813-1820
    CrossrefPubMedGoogle Scholar
  • 9 Chang S L, Lin J G, Chi T C, Liu I M, Cheng J T. An insulin-dependent hypoglycemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats.  Diabetologia. 1999;  42 250-255
    CrossrefPubMedGoogle Scholar
  • 10 Bailey C J. Biguanides and NIDDM.  Diabetes Care. 1992;  15 755-772
    CrossrefPubMedGoogle Scholar
  • 11 Wiernsperger N. Preclinical pharmacology of biguanides.  Handb Exp Pharmacol. 1996;  119 305-358
    PubMedGoogle Scholar
  • 12 Scheen A J, Letiexhe M R, Lefebvre P J. Effects of metformin in obese patients with impaired glucose tolerance.  Diabetes Metab Rev. 1995;  11 S69-S80
    PubMedGoogle Scholar
  • 13 DeFronzo R A. Pathogenesis of type 2 diabetes. Implications for metformin.  Drugs. 1999;  58 (Suppl. 1) 29-30
    PubMedGoogle Scholar
  • 14 Wiernsperger N, Bailey C. The antihyperglycaemic effect of metformin.  Drugs. 1999;  58 (Suppl. 1) 31-39
    PubMedGoogle Scholar
  • 15 Raptis A E, Tountas N B, Yalouris A G, Halvatsiotis P G, Raptis S A. Therapeutic effect of glibenclamide in a fixed combination with metformin or phenformin in NIDDM patients.  Horm Metab Res. 1996;  28 89-94
    PubMedGoogle Scholar
  • 16 Consoli A, Nurjhan N, Capani F, Gerich J. Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM.  Diabetes. 1989;  38 550-557
    CrossrefPubMedGoogle Scholar
  • 17 Attwood P A, Keech D B. Pyruvate carboxylase.  Curr Top Cell Regul. 1984;  23 1-55
    PubMedGoogle Scholar
  • 18 Hanson R W, Reshef L. Regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression.  Annu Rev Biochem. 1997;  66 581-611
    CrossrefPubMedGoogle Scholar
  • 19 Kolterman O G, Gray R S, Griffen J, Burstein P, Insel J, Scarlett J A, Olefsky J M. Receptor and post-receptor defects contribute to the insulin resistance in noninsulin-dependent diabetes mellitus.  J Clin Invest. 1981;  68 967-969
    PubMedGoogle Scholar
  • 20 DeFronzo R A, Bonadonna R C, Ferrannini E. Pathogenesis of NIDDM: A balanced overview.  Diabetes Care. 1992;  15 318-353
    CrossrefPubMedGoogle Scholar
  • 21 Large V, Beylot M. Modifications of citric acid cycle activity and gluconeogenesis in streptozotocin-induced diabetes and effects of metformin.  Diabetes. 1999;  48 1251-1257
    PubMedGoogle Scholar
  • 22 Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich J E. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus.  N Engl J Med. 1995;  301 550-554
    PubMedGoogle Scholar
  • 23 Meyer F, Ipaktchi M, Clauser H. Specific inhibition of gluconeogenesis by biguanides.  Nature. 1967;  213 203-204
    PubMedGoogle Scholar
  • 24 Chang H M, But P PH. Pharmacology and applications of Chinese material medica (Vol 1).  Beijing:; People's Medical Publishing House, 1983
    Google Scholar

Prof. Juei-Tang Cheng

Department of Pharmacology
College of Medicine
National Cheng Kung University

Tainan City
Taiwan 70101
R.O.C.


Phone: + 886 (6) 237 27 06

Fax: + 886 (6) 238 65 48

Email: jtcheng@mail.ncku.edu.tw