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.

Herb–Drug Interaction of Red Ginseng Extract and Ginsenoside Rc with Valsartan in Rats

“…The selected RGE dose in this study is in the range of effective dose without significant toxicity and showed similar plasma concentrations of Rb1, Rb2, and Rc (5.3-15.8 nM in rats and 6.2-12.7 nM in human subjects) [19,33]. In numerous animal studies, the RGE dose has ranged from 200 mg/kg to 2.0 g/kg (i.e., 3-15 mg/kg of total ginsenosides) [36,37]. In human studies, RGE was administered to diabetic patients for 4 to 24 weeks at doses of 2.7-6.0g/day, which usually contained 50-100 mg ginsenosides/day [20,38].…”

Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract

“…Korean red ginseng may benefit mice with streptozotocin-induced diabetes owing to its hypoglycemic and immunomodulatory effects [12]. Supplementation with Korean red ginseng extract (RGE), fermented red ginseng, and black ginseng also has been shown to improve type 1 and type 2 diabetic conditions in both animals [12,13,14] and humans [15,16,17].…”

“…The selected RGE dose in this study is in the range that shows anti-diabetic effect. In numerous animal studies that showed anti-diabetic effect of RGE, the RGE dose has ranged from 200 mg/kg to 2.0 g/kg (i.e., 3–15 mg/kg of total ginsenosides) [14,25,26,27]. In human studies, RGE was administered to diabetic patients for 4 to 24 weeks at doses of 2.7 g–6.0g/day, which usually contained 50–100 mg ginsenosides/day [16,17,23].…”

Naringenin downregulates inflammation‐mediated nitric oxide overproduction and potentiates endogenous antioxidant status during hyperglycemia

“…Group 2 was marked as diabetic control group in which no therapeutic intervention was made throughout the study period. Further, Group 3 was marked as standardtreated group, and this group was treated with metformin as standard drug with a dose of 50 mg kg −1 day −1 (Nam et al, 2018).…”