Effects of Bofutsushosan and Gardeniae Fructus on Diabetic Serum Parameters in Streptozotocin-Induced Diabetic Mice

Abstract

Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風通聖散) and its composed crude drug, gardeniae fructus (GF: 山梔子) were investigated on levels of these diabetic parameters (serum glucose, insulin, triglyceride and cholesterol) in STZ-diabetic mice. BOF and GF were extracted in 10 volumes of distilled water with an automatic extractor “Torobi”. STZ-induced diabetic mice with serum glucose level of over 600 mg/dl at 3 - 4 weeks after intravenous injection of 150 mg/kg STZ were used for experiments. BOF extract, GF extract, geniposide (a main constituent of GF), and glibenclamide were administered intraperitoneally into 3-hour-fasted STZ-diabetic mice. At 6 hours after administration, BOF extract (100 - 300 mg/kg) decreased high levels of serum glucose, triglyceride and cholesterol, and also increased low level of serum insulin in STZ-diabetic mice in a dose-dependent manner, respectively. Anti-diabetic drug glibenclamide (0.3 - 1 mg/kg) as positive control significantly decreased serum glucose and cholesterol levels, and increased serum insulin level in the diabetic mice. GF extract (30 - 300 mg/kg) decreased serum glucose, triglyceride and cholesterol levels but did not affect serum insulin level in the diabetic mice. Geniposide (10 - 100 mg/kg), decreased serum glucose level but did not affect serum insulin and triglyceride levels in the diabetic mice. These results demonstrated that intraperitoneally administrated BOF extract improved abnormal levels of serum glucose, insulin, triglyceride and cholesterol in the STZ-diabetic mice as being similar to glibenclamide. GF extract has an important role in a part of improving actions of BOF in the diabetic mice. The action of GF extract on serum glucose was parallel with the action of geniposide in the diabetic mice, supporting roles of geniposide in anti-hyperglycemic action of GF.

Share and Cite:

Yu, Q. , Yasuda, M. , Takahashi, T. , Nomura, M. , Hagino, N. and Kobayashi, S. (2011) Effects of Bofutsushosan and Gardeniae Fructus on Diabetic Serum Parameters in Streptozotocin-Induced Diabetic Mice. Chinese Medicine, 2, 130-137. doi: 10.4236/cm.2011.24022.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] M. Brownlee, “Biochemistry and Molecular Cell Biology of Diabetic Complications,” Nature, Vol. 414, 2001, pp. 813-820. doi:10.1038/414813a
[2] S. Kobayashi, M. Suzuki, H. Tsuneki, R. Nagai, S. Horiuchi and N. Hagino, “Overproduction of Nε-(Carboxymethyl)lysine-Induced Neovascularization in Cultured Choroidal Explant of Streptozotocin-Diabetic Rat,” Biological & Pharmaceutical Bulletin, Vol. 27, No. 10, 2004, pp. 1565-1571. doi:10.1248/bpb.27.1565
[3] Y. Yamamoto, I. Kato, T. Doi, H. Yonekura, S. Ohashi, M. Takeuchi, T. Watanabe, S. I. Yamagishi, S. Sakurai, S. Takasawa, H. Okamoto and H. Yamamoto, “Development and Prevention of Advanced Diabetic Nephropathy in RAGE-Overexpressing Mice,” The Journal of Clinical Investigation, Vol. 108, 2001, pp. 261-268.
[4] N. E. Cameron and M. A. Cotter, “Effects of Antioxidants on Nerve and Vascular Dysfunction in Experimental Diabetes,” Diabetes Research and Clinical Practice, Vol. 45, No. 2, 1999, pp. 137-146. doi:10.1016/S0168-8227(99)00043-1
[5] L. J. Copp. ey, J. S. Gellett, E. P. Davidson, J. A. Dunlap, D. D. Lund and M. A. Yorek, “Effect of Antioxidant Treatment of Streptozotocin-Induced Rats on Endoneurial Blood Flow, Motor Nerve Condition Velocity, and Vascular Reactivity of Epineurial Arterioles of the Sciatic Nerve,” Diabetes, Vol. 50, No. 8, 2001, pp. 1927-1937. doi:10.2337/diabetes.50.8.1927
[6] S. Yagihashi, S. I. Yamagishi, R. I. Wada, M. Baba, T. C. Hohman, C. Yabe-Nishimura and Y. Kokai, “Neuropathy in Diabetic Mice Overexpressing Human Aldose Reductase and Effects of Aldose Reductase Inhibitor,” Brain, Vol. 124, No. 12, 2001, pp. 2448-2458. doi:10.1093/brain/124.12.2448
[7] I. G. Obrosova, C. Van Huysen, L. Fathallah, X. Cao, D. A. Greene and M. J. Stevens, “An Aldose Reductase Inhibitors Reverses Early Diabetes-Induced Changes in Peripheral Nerve Function, Metabolism and Antioxidative Defense,” The FASEB Journal, Vol. 16, 2002, pp. 123- 125.
[8] P. Xia, T. Inoguchi, S. Kern, R. L. Engerman, P. J. Oates and G. L. King, “Characterization of the Mechanism of the Chronic Activation of Diacylglycerol Protein Kinase C Pathway in Diabetes and Hypergalactosomia,” Diabetes, Vol. 43, No. 9, 1994, pp. 1122-1129. doi:10.2337/diabetes.43.9.1122
[9] G. Booth, T. J. Stalker, A. M. Lefer and R. Scalia, “Mechanisms of Amelioration of Glucose-Induced Endothelial Dysfunction Following Inhibition of Protein Kinase C in vivo,” Diabetes, Vol. 51, No. 5, 2002, pp. 1556-1564. doi:10.2337/diabetes.51.5.1556
[10] G. M. Reaven, “Banting Lecture 1988. Role of Insulin Resistance in Human Disease,” Diabetes, Vol. 37, No. 12, 1988, pp. 1595-1607. doi:10.2337/diabetes.37.12.1595
[11] W. V. Brown, “Lipoprotein Disorders in Diabetes Mellitus,” Medical Clinics of North America, Vol. 78, 1994, pp. 143-161.
[12] I. I. Kessler, “Mortality Experience of Diabetic Patients. A Twenty-Six-Year Follow-up Study,” The American Journal of Medicine, Vol. 51, No. 6, 1971, pp. 715-724. doi:10.1016/0002-9343(71)90299-3
[13] L. J. Bennion, “Effects of Diabetes mellitus on Cholesterol Metabolism in Man,” The New England Journal of Medicine, Vol. 296, 1977, pp. 1365-1371. doi:10.1056/NEJM197706162962401
[14] P. Kundsen, J. Ericksson, S. Lahdenpera, J. Kahri, L. Groop and M. R. Taskinen, “Changes of Lipolytic Enzymes Cluster with Insulin Resistance Syndrome. Botnia Study Group,” Diabetologia, Vol. 38, No. 3, 1995, pp. 344-350. doi:10.1007/BF00400640
[15] S. M. Grandy, I. J. Benjamin, G. L. Burke, A. Chait, R. H. Eckel, B. V. Howard, W. Mitch, S. C. Smith Jr. and J. R. Sowers, “Diabetes and Cardiovascular Disease: A Statement for Healthcare Professionals from the American Heart Association,” Circulation, Vol. 100, 1999, pp. 1134-1146.
[16] P. Libby and J. Plutzky, “Diabetic Macrovascular Disease: The Glucose Paradox?” Circulation, Vol. 106, 2002, pp. 2760-2763. doi:10.1161/01.CIR.0000037282.92395.AE
[17] A. Sachin, K. O. Shreesh and V. Divya, “Characterization of Streptozotocin Induced Diabetes Mellitus in Swiss Albino Mice,” Global Journal of Pharmacology, Vol. 3, 2009, pp. 81-84.
[18] K. Srinivasan, B. Viswanad, L. Asrat, C. L. Kaul and P. Ramarao, “Combination of High-Fat Diet-Fed and Low-Dose Streptozotocin-Treated Rat: A Model for Type 2 Diabetes and Pharmacological Screening,” Pharmacological Research, Vol. 52, No. 4, 2005, pp. 313-320. doi:10.1016/j.phrs.2005.05.004
[19] R. N. Wan, L. Bouwens and G. Kloppel, “Beta Cell Proliferation in Normal and Streptozotocin-Treated New Born Rats. Site, Dynamics and Capacity,” Diabetologia, Vol. 37, No. 11, 1994, pp. 1088-1090. doi:10.1007/BF00418372
[20] A. Junod, A. E. Lambert, L. Orci, R. Pictet, A. E. Gonet and A. E. Renold, “Studies of the Diabetogenic Action of Streptozotocin,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 126, 1967, pp. 201- 205.
[21] C. Hioki, K. Yoshimoto and T. Yoshida, “Efficacy of Bofu-Tsusho-San, an Oriental Herbal Medicine, in Obese Japanese Women with Impaired Glucose Tolerance,” Clinical and Experimental Pharmacology and Physiology, Vol. 31, No. 9, 2004, pp. 614-619. doi:10.1111/j.1440-1681.2004.04056.x
[22] C. Y. Zhang, L. E. Parton, C. P. Ye, S. Krauss, R. Shen, C. T., Lin, J. A. Porco Jr. and B. B. Lowell, “Genipin Inhibits UCPs-Mediated Proton Leak and Acutely Reverses Obesity- and Glucose-Induced B Cell Dysfunction in Isolated Pancreatic Islets,” Cell Metabolism, Vol. 3, No. 6, 2006, pp. 417-427. doi:10.1016/j.cmet.2006.04.010
[23] Y. Y. Liu, S. Kobayashi, T. Tsutsumi and H. Kontani, “Combined Effects of Stephania Radix and Astragali Radix in Antihyperglycemic Action of Boi-ogi-to (Fang- ji-huang-qi-tang) in Streptozotocin-Induced Diabetic Mice,” Journal of Traditional Medicines, Vol. 17, 2000, pp. 253-260.
[24] T. Tsutsumi, S. Kobayashi, Y. Y. Liu and H. Kontani, “Anti-Hyperglycemic Effect of Fangchinoline Isolated from Stephania Tetrandra Radix in Streptozotocin-Diabetic Mice,” Biological & Pharmaceutical Bulletin, Vol. 26, No. 3313, 2003, pp. 313-317. doi:10.1248/bpb.26.313
[25] S. I. Taylor, “Deconstructing Type 2 Diabetes,” Cell, Vol. 97, 1999, pp. 9-12. doi:10.1016/S0092-8674(00)80709-6
[26] I. Kimura, N. Nakashima, Y. Sugihara, F. J. Chen and M. Kimura, “The Antihyperglycaemic Blend Effect of Traditional Chinese Medicine Byakko-Kaninjin-to on Alloxan and Diabetic KK-CAy Mice,” Phytotherapy Research, Vol. 13, No. 6, 1999, pp. 484-488. doi:10.1002/(SICI)1099-1573(199909)13:6<484::AID-PTR485>3.0.CO;2-X
[27] H. J. Wang, Y. X. Jin, W. Shen, J. Neng, T. Wu, Y. J. Li and Z. W. Fu, “Low Dose Streptozotocin (STZ) Combined with High Energy Intake Can Effectively Induce Type 2 Diabetes through Altering the Related Gene Expression,” Asia Pacific Journal of Clinical Nutrition, Vol. 16, 2007, pp. 412-417.
[28] C. Y. Zhang, G. Baffy, P. Perret, S. Krauss, O. Peroni, D. Grujic, T. Hagen, A. J. Vidal-Puig, O. Boss and Y. B. Kim, “Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, Beta Cell Dysfunction, and Type 2 Diabetes,” Cell, Vol. 105, No. 6, 2001, pp. 745-755. doi:10.1016/S0092-8674(01)00378-6
[29] Y. Emre, C. Hurtaud, M. Karaca, T. Nubel, F. Zavala and D. Ricquier, “Role of Uncoupling Protein UCP2 in Cell-Mediated Immunity: How Macrophage-Mediated Insulitis Is Accelerated in a Model of Autoimmune Diabetes,” The Proceedings of the National Academy of Sciences U.S.A., Vol. 27, 2007, pp. 19085-19090.
[30] H. Kageyama, A. Suga, M. Kashiba, J. Oka, T. Osaka, T. Kashiwa, T. Hirano, K. Nemoto, Y. Namba, D. Ricquier, J.-P. Giacobino and S. Inoue, “Increased Uncoupling Protein-2 and -3 Gene Expressions in Skeletal Muscle of STZ-Induced Diabetic Rats,” The Federation of European Biochemical Societies Letters, Vol. 440, No. 3, 1998, pp. 450-453. doi:10.1016/S0014-5793(98)01506-3
[31] J. D. Turner, L. D. Gaspers, G. Wang and A. P. Thomas, “Uncoupling Protein-2 Modulates Myocardial Excitation-Contraction Coupling,” Circulation Research, Vol. 106, 2010, pp. 730-738. doi:10.1161/CIRCRESAHA.109.206631
[32] R. J. Mailloux, C. N.-K. Adjeitey and M.-E. Harper, “Genipin-Induced Inhibition of Uncoupling Protein-2 Sensitizes Drug-Resistant Cancer Cells to Toxic Agents,” PLoS ONE, Vol. 5, 2010, pp. 1-10. doi:10.1371/journal.pone.0013289

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.