Ginsenoside Rh2 is One of the Active Principles of Panax Ginseng Root to Improve Insulin Sensitivity in Fructose-rich Chow-fed Rats

Abstract

Ginsenoside Rh2, one of the ginsenosides contained in the Panax ginseng root, was employed to screen the effect on insulin resistance of rats induced by a diet containing 60% fructose. Single intravenous injection of ginsenoside Rh2 decreased the plasma glucose concentrations in 60 minutes in a dose-dependent manner from 0.1 mg/kg to 1 mg/kg in rats with insulin resistance induced by fructose-rich chow. Repeated intravenous injection of ginsenoside Rh2 (1 mg/kg per injection, 3 times daily) into rats which received fructose-rich chow for 3 consecutive days decreased the value of glucose-insulin index, the product of the areas under the curve of glucose and insulin during the intraperitoneal (i.p.) glucose tolerance test. This means that ginsenoside Rh2 has an ability to improve insulin action on glucose disposal. The plasma glucose lowering action of tolbutamide, induced by the secretion of endogenous insulin, is widely used to characterize the formation of insulin resistance. Time for the loss of plasma glucose lowering response to tolbutamide (10 mg/kg, i.p.) in rats during insulin resistance induction by fructose-rich chow was also markedly delayed by the repeated treatment of ginsenoside Rh2, as compared to the vehicle-treated control. Thus, the repeated treatment of ginsenoside Rh2 delayed the development of insulin resistance in high fructose feeding rats. Increase of insulin sensitivity by ginsenoside Rh2 was further identified using the plasma glucose lowering action of exogenous insulin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Repeated injection of ginsenoside Rh2 at the same dosing (1 mg/kg, 3 times daily) into STZ-diabetic rats for 10 days made an increase of the responses to exogenous insulin. Taken together, it can be concluded that ginsenoside Rh2 has an ability to improve insulin sensitivity and it seems suitable to use ginsenoside Rh2 as an adjuvant for diabetic patients and/or the subjects wishing to increase insulin sensitivity.

fructose-rich chow - ginsenoside Rh2 - insulin resistance - intraperitoneal glucose tolerance test - tolbutamide

References

• 1 Kruszynska YT, Olefsky JM. Cellular and molecular mechanisms of non-insulin dependent diabetes mellitus.  J Invest Med. 1996;  44 413-428
• 2 Henriksen EJ. Invited review: Effects of acute exercise and exercise training on insulin resistance.  J Appl Physiol. 2002;  93 788-796
• 3 Kennedy DO, Scholey AB. Ginseng: potential for the enhancement of cognitive performance and mood.  Pharmacol Biochem Behav. 2003;  75 687-700
• 4 Block KI, Mead MN. Immune system effects of echinacea, ginseng, and astragalus: a review.  Integr Cancer Ther. 2003;  2 247-267
• 5 Van Kampen J, Robertson H, Hagg T, Drobitch R. Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson's disease.  Exp Neurol. 2003;  2 521-529
• 6 Kiefer D, Pantuso T. Panax ginseng.  Am Fam Physician. 2003;  68 1539-1542
• 7 Kimura M, Waki I, Tanaka O, Nagai Y, Shibata S. Pharmacological sequential trials for the fractionation of components with hypoglycemic activity in alloxan diabetic mice from ginseng radix.  J Pharmacobiodyn. 1981;  4 402-409
• 8 Kimura M, Suzuki J. The pattern of action of blended Chinese traditional medicines to glucose tolerance curves in genetically diabetic KK-CA^y mice.  J Pharmacobiodyn. 1981;  4 907-915
• 9 Yokozawa T, Kobayashi T, Oura H, Kawashima Y. Studies on the mechanism of the hypoglycemic activity of ginsenoside-Rb₂ in streptozotocin diabetic rats.  Chem Pharm Bull. 1985;  33 869-872
• 10 Kahn SE. Clinical review 135: the importance of beta-cell failure in the development and progression of type 2 diabetes.  J Clin Endocrinol Metab. 2001;  86 4047-4058
• 11 Kahn CR. Banting Lecture: insulin action, diabetogenes, and the cause of type 2 diabetes.  Diabetes. 1994;  43 1066-1084
• 12 Liu TP, Liu IM, Cheng JT. Improvement of insulin resistance by panax ginseng in fructose-rich chow-fed rats.  Horm Metab Res. 2005;  37 146-151
• 13 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions.  Biochem Pharmacol. 1999;  58 1685-1693
• 14 Lee KY, Park JA, Chung E, Lee YH, Kim SI, Lee SK. Ginsenoside-Rh2 blocks the cell cycle of SK-HEP-1 cells at the G1/S boundary by selectively inducing the protein expression of p27kip1.  Cancer Lett. 1996;  110 93-200
• 15 Park EK, Choo MK, Kim EJ. Antiallergic activity of ginsenoside Rh2.  Biol Pharm Bull. 2003;  26 1581-1584
• 16 Lee WK, Kao ST, Liu IM, Cheng JT. Increase of insulin secretion by ginsenoside Rh2 to lower plasma glucose in Wistar rats.  Clin Exp Pharmacol Physiol. 2006;  33 27-32
• 17 Le KA, Tappy L. Metabolic effects of fructose.  Curr Opin Clin Nutr Metab Care. 2006;  9 469-475
• 18 Chang JC, Wu MC, Liu IM, Cheng JT. Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats.  Horm Metab Res. 2005;  37 610-616
• 19 Ahren B, Pacini G. Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies.  Eur J Endocrinol. 2004;  150 97-104
• 20 Bessesen DH. The role of carbohydrates in insulin resistance.  J Nutr. 2001;  131 S2782-S2786
• 21 Cox KL, Burke V, Morton AR, Beilin LJ, Puddey IB. Independent and additive effects of energy restriction and exercise on glucose and insulin concentrations in sedentary overweight men.  Am J Clin Nutr. 2004;  80 308-316
• 22 Younis N, Soran H, Farook S. The prevention of type 2 diabetes mellitus: recent advances.  QJM. 2004;  97 451-455
• 23 Korenaga M, Kawaguchi K, Korenaga K, Uchida K, Sakaida I. Insulin sensitizer-anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance.  Nippon Rinsho. 2006;  64 1157-1164
• 24 Musi N, Goodyear LJ. Insulin resistance and improvements in signal transduction.  Endocrine. 2006;  29 73-80
• 25 Hasegawa H, Lee KS, Nagaoka T, Tezuka Y, Uchiyama M, Kadota S, Saiki I. Pharmacokinetics of ginsenoside deglycosylated by intestinal bacteria and its transformation to biologically active fatty acid esters.  Biol Pharm Bull. 2000;  23 298-304
• 26 Bae EA, Han MJ, Choo MK, Park SY, Kim DH. Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities.  Biol Pharm Bull. 2002;  25 58-63
• 27 Nakata H, Kikuchi Y, Tode T, Hirata J, Kita T, Ishii K, Kudoh K, Nagata I, Shinomiya N. Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells.  Jpn J Cancer Res. 1998;  89 733-740

Correspondence