Effect of Red Ginseng Extract on the Pharmacokinetics and Efficacy of Metformin in Streptozotocin-Induced Diabetic Rats

Abstract

The purpose of this study was to investigate the effect of red ginseng extract on the pharmacokinetics (PK) and efficacy of metformin in streptozotocin-induced diabetic rats. The diabetes mellitus rat model was established by intraperitoneally administering multiple doses of streptozotocin (30 mg/kg, twice on day 1 and 8), and diabetic rats received metformin 50 mg/kg with or without single or multiple administration of Korean red ginseng extract (RGE, 2 g/kg/day, once or for 1 week). RGE administration did not affect the plasma concentration and renal excretion of metformin. Further, diabetic rats were administered metformin (50 mg/kg) and RGE (2 g/kg) alone or concomitantly for 5 weeks, and both regimens decreased the fasting blood glucose and glycated hemoglobin (Hb-A1c) levels. Furthermore, fasting blood glucose levels were reduced by metformin or RGE administered alone but recovered to the control level following co-administration, suggesting that the effect was additive. However, triglyceride and free fatty acid levels were not different with metformin and RGE treatment alone or in combination. Biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol levels were not different among the three treatment groups. In conclusion, RGE and metformin showed an additive effect in glycemic control. However, the co-administration of RGE and metformin did not cause PK interactions or affect biochemical parameters including the free fatty acid, triglyceride, AST, ALT, or cholesterol levels.

Keywords: Korean red ginseng extract; diabetes; drug interaction; efficacy; metformin; pharmacokinetics.

Figure 1

Plasma concentration-time profile of metformin after single oral administration (50 mg/kg) alone (●, control) and following single (○, SA) or multiple administration (▼, 1WRA) of red ginseng extract (RGE, 2 g/kg/day) in streptozotocin (STZ)-induced diabetic rats. Data points are means ± SD of five rats.

Figure 2

Plasma concentration–time profile of ginsenoside Rb1 following a single oral dose of RGE (2 g/kg) in the absence or presence of metformin (50 mg/kg) in streptozotocin (STZ)-induced diabetic rats. Data points are means ± SD of five rats.

Figure 3

Effects of oral administration of metformin (M) and red ginseng extract (RGE) alone or combined on fasting blood glucose concentration of normal control (---), streptozotocin (STZ)-induced diabetic group (●, DC), diabetic rats treated with metformin (○, D + M, 50 mg/kg/day), diabetic rats supplemented with RGE (▼, D + RGE, 2 g/kg/day), and diabetic rats treated with metformin and RGE (∆, D + RGE + M). Data points are means ± SD of four different rats per group. * p < 0.05 compared with DC group; + p < 0.05 compared with D + M group; # p < 0.05 compared with D + RGE group using two-way ANOVA test.

Figure 4

Effects of oral administration of metformin and red ginseng extract (RGE) alone or combined on body (A) and liver or pancreas (B) weights in normal control, streptozotocin (STZ)-induced diabetic group (DC), diabetic rats treated with metformin (D + M, 50 mg/kg/day), diabetic rats supplemented with RGE (D + RGE, 2 g/kg/day), and diabetic rats treated with metformin and RGE (D + RGE + M). Data points and bars are means ± SD of four rats per group.

Figure 5

Biochemical parameters, alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose, triglyceride, free fatty acid, hemoglobin-A1c (Hb-A1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol levels in normal control, streptozotocin (STZ)-induced diabetic group (DC), diabetic rats treated with metformin (D + M), diabetic rats supplemented with RGE (D + RGE), and diabetic rats treated with metformin and RGE (D + RGE + M). Bars represent means ± SD of four rats per group; * p < 0.05 compared with control group using Student’s t-test; + p < 0.05 compared with DC group using Student’s t-test.