Antidiabetic Effects of Panax ginseng Berry Extract
We evaluated antihyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On day 12, 150 mg/kg extract–treated ob/ob mice became normoglycemic (137 ± 6.7 mg/dl) and had significantly improved glucose tolerance. The overall glucose excursion during the 2-h intraperitoneal glucose tolerance test decreased by 46% (P < 0.01) compared with vehicle-treated ob/ob mice. The improvement in blood glucose levels in the extract-treated ob/ ob mice was associated with a significant reduction in serum insulin levels in fed and fasting mice. A hyperinsulinemic-euglycemic clamp study revealed a more than twofold increase in the rate of insulin-stimulated glucose disposal in treated ob/ ob mice (112 ± 19.1 vs. 52 ± 11.8 µmol · kg · min for the vehicle group, P < 0.01). In addition, the extract-treated ob/ob mice lost a significant amount of weight (from 51.7 ± 1.9 g on day 0 to 45.7 ± 1.2 on day 12, P < 0.01 vs. vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P < 0.05) and a very significant increase in energy expenditure (P < 0.01) and body temperature (P < 0.01). Treatment with the extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re plays a significant role in antihyperglycemic action. This antidiabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism.
Diabetes is a major health problem, affecting ~5% of the total population in the U.S. and 3% of the population worldwide. Over 90% of patients with diabetes have type 2 diabetes; the remainder have type 1 diabetes. Although the two types of diabetes have distinct pathogeneses, hyperglycemia and various life-threatening complications resulting from long-term hyperglycemia are the most common features. Epidemiological studies and clinical trials strongly support the notion that hyperglycemia is the principal cause of complications. Effective blood glucose control is the key to preventing or reversing diabetic complications and improving quality of life in patients with diabetes . Thus, sustained reductions in hyperglycemia will decrease the risk of developing microvascular complications and most likely reduce the risk of macrovascular complications .
The ability of insulin to mediate tissue glucose uptake is a critical step in maintaining glucose homeostasis and in clearing the postprandial glucose load . Patients with type 2 diabetes exhibit a marked reduction in insulin-mediated glucose disposal . Although insulin resistance is independently associated with obesity, which exists in 80% of type 2 diabetic patients in the West , it is more severe in obese patients .
Historical records reveal that in traditional medical systems, a disease similar to type 2 diabetes was treated with plant extracts . For example, the root of Panax ginseng, or Asian ginseng, has been used clinically to treat type 2 diabetes and has also been used as a tonic, often taken for years without evidence of adverse effects or toxicity . Results of in vitro and in vivo animal studies and clinical trials support the claim that the root of Panax ginseng and the root of other ginseng species (e.g., Panax quinquefolius, or American ginseng) possess antihyperglycemic activity. However, most in vivo animal studies have used type 1, not type 2, diabetic models. In addition, these previous studies have not investigated the mechanisms responsible for the antidiabetic effects of Panax ginseng, which are yet unknown.
The active components of ginseng are considered to be ginsenosides, a group of steroidal saponins . Ginsenosides are distributed in many parts of the ginseng plant, including the root, leaf, and berry. Different parts of the plant contain distinct ginsenoside profiles , and these parts may have different pharmacological activities. The root of ginseng is a commonly used herbal medicine. Whether Panax ginseng berry exhibits significantly more potent antihyperglycemic activity than the root has not been explored. The identification of compounds from ginseng with antihyperglycemic activity may also provide an opportunity to develop a new class of antidiabetic agent.
This study sought to determine whether Panax ginseng berry extract normalizes hyperglycemia and reduces body weight in an animal model with type 2 diabetes. We used the ob/ob mouse model, which exhibits profound obesity and insulin resistance . In ob/ob mice, mutation of the obese gene leads to morbid obesity and metabolic abnormalities, such as hyperglycemia, glucose intolerance, and hyperinsulinemia, that phenotypically resemble human type 2 diabetes. In addition, these mice exhibit reduced metabolism and body temperature. We also explored the mechanisms responsible for glucose homeostasis by measuring in vivo insulin-stimulated glucose disposal, body weight regulation, and energy expenditure changes. Finally, we examined whether ginsenoside Re, a major constituent from the berry only, plays an important role in antihyperglycemic activity.
We evaluated antihyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On day 12, 150 mg/kg extract–treated ob/ob mice became normoglycemic (137 ± 6.7 mg/dl) and had significantly improved glucose tolerance. The overall glucose excursion during the 2-h intraperitoneal glucose tolerance test decreased by 46% (P < 0.01) compared with vehicle-treated ob/ob mice. The improvement in blood glucose levels in the extract-treated ob/ ob mice was associated with a significant reduction in serum insulin levels in fed and fasting mice. A hyperinsulinemic-euglycemic clamp study revealed a more than twofold increase in the rate of insulin-stimulated glucose disposal in treated ob/ ob mice (112 ± 19.1 vs. 52 ± 11.8 µmol · kg · min for the vehicle group, P < 0.01). In addition, the extract-treated ob/ob mice lost a significant amount of weight (from 51.7 ± 1.9 g on day 0 to 45.7 ± 1.2 on day 12, P < 0.01 vs. vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P < 0.05) and a very significant increase in energy expenditure (P < 0.01) and body temperature (P < 0.01). Treatment with the extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re plays a significant role in antihyperglycemic action. This antidiabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism.
Diabetes is a major health problem, affecting ~5% of the total population in the U.S. and 3% of the population worldwide. Over 90% of patients with diabetes have type 2 diabetes; the remainder have type 1 diabetes. Although the two types of diabetes have distinct pathogeneses, hyperglycemia and various life-threatening complications resulting from long-term hyperglycemia are the most common features. Epidemiological studies and clinical trials strongly support the notion that hyperglycemia is the principal cause of complications. Effective blood glucose control is the key to preventing or reversing diabetic complications and improving quality of life in patients with diabetes . Thus, sustained reductions in hyperglycemia will decrease the risk of developing microvascular complications and most likely reduce the risk of macrovascular complications .
The ability of insulin to mediate tissue glucose uptake is a critical step in maintaining glucose homeostasis and in clearing the postprandial glucose load . Patients with type 2 diabetes exhibit a marked reduction in insulin-mediated glucose disposal . Although insulin resistance is independently associated with obesity, which exists in 80% of type 2 diabetic patients in the West , it is more severe in obese patients .
Historical records reveal that in traditional medical systems, a disease similar to type 2 diabetes was treated with plant extracts . For example, the root of Panax ginseng, or Asian ginseng, has been used clinically to treat type 2 diabetes and has also been used as a tonic, often taken for years without evidence of adverse effects or toxicity . Results of in vitro and in vivo animal studies and clinical trials support the claim that the root of Panax ginseng and the root of other ginseng species (e.g., Panax quinquefolius, or American ginseng) possess antihyperglycemic activity. However, most in vivo animal studies have used type 1, not type 2, diabetic models. In addition, these previous studies have not investigated the mechanisms responsible for the antidiabetic effects of Panax ginseng, which are yet unknown.
The active components of ginseng are considered to be ginsenosides, a group of steroidal saponins . Ginsenosides are distributed in many parts of the ginseng plant, including the root, leaf, and berry. Different parts of the plant contain distinct ginsenoside profiles , and these parts may have different pharmacological activities. The root of ginseng is a commonly used herbal medicine. Whether Panax ginseng berry exhibits significantly more potent antihyperglycemic activity than the root has not been explored. The identification of compounds from ginseng with antihyperglycemic activity may also provide an opportunity to develop a new class of antidiabetic agent.
This study sought to determine whether Panax ginseng berry extract normalizes hyperglycemia and reduces body weight in an animal model with type 2 diabetes. We used the ob/ob mouse model, which exhibits profound obesity and insulin resistance . In ob/ob mice, mutation of the obese gene leads to morbid obesity and metabolic abnormalities, such as hyperglycemia, glucose intolerance, and hyperinsulinemia, that phenotypically resemble human type 2 diabetes. In addition, these mice exhibit reduced metabolism and body temperature. We also explored the mechanisms responsible for glucose homeostasis by measuring in vivo insulin-stimulated glucose disposal, body weight regulation, and energy expenditure changes. Finally, we examined whether ginsenoside Re, a major constituent from the berry only, plays an important role in antihyperglycemic activity.
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