Sung Hyun Chung

Comparisons between white ginseng radix and rootlet for antidiabetic activity and mechanism in KKAy mice

The mechanisms responsible for the antidiabetic activity of both the white ginseng radix (Ginseng Radix Alba, GRA) and the rootlet (Ginseng Radix Palva, GRP) were investigated. After a four week oral administration, the fasting blood glucose levels in the GRA- and GRP-treated groups were lower when compared to the control group. To elucidate the hypoglycemic mechanism(s) of the ginseng radices, glucose absorption from the small intestine, hepatic hexokinase and glucose-6-phosphatase activities, in addition to PPAR-γ expression in adipose tissue were examined. The results strongly suggest that GRA can improve hyperglycemia in KKAy mice, possibly by blocking intestinal glucose absorption and inhibiting hepatic glucose-6-phosphatase, and GRP through the upregulation of adipocyte PPAR-γ protein expression as well as inhibiting intestinal glucose absorption.

Wild Ginseng Prevents the Onset of High-Fat Diet Induced Hyperglycemia and Obesity in ICR Mice

Ginseng is a shade-loving perennial herb that is cultivated mainly in Korea, Japan, and China. The ginseng root has been used as a tonic remedy, and its antidiabetic activity has been demonstrated as early as 1920s. Although wild ginseng was anecdotally thought to be superior to cultivated ginseng as far as pharmacological properties were concerned, there have been no prior reports on the antidiabetic effect of wild ginseng. In this study, we investigated the preventative anti-diabetic and anti-obese effects of wild ginseng ethanol extract (WGEE). In the preventive experiment, WGEE co-administered with a high fat diet significantly inhibited body weight gain, fasting blood glucose, triglyceride, and free fatty acid levels in a dose dependent manner. WGEE-treated mice at doses of 250 and 500 mg/kg improved the insulin resistance index by 55% and 61% compared to the high fat diet (HFD) control, respectively. Diameters of white and brown adipocytes were also decreased by 62% and 46% in the WG500-treated group compared to those in HFD fed control mice. Taken together, WGEE has potential as a preventive agent for type 2 diabetes mellitus (and possibly obesity) and deserves clinical trial in the near future.

Salicornia herbacea prevents high fat diet-induced hyperglycemia and hyperlipidemia in ICR mice.

Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by living in coastal areas.S. herbacea (SH) has been demonstrated to stimulate cytokine production, nitric oxide release, and to show anti-oxidative effect. In a series of investigations to develop potential anti-diabetic and/or anti-hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract ofSalicomia herbacea was found to prevent the onset of the hyperglycemia and hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice were randomly divided into five groups; two control and three treatment groups. The control mice were to receive either a regular diet (RD) or high-fat diet (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg, 700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of metformin (MT250) for a 10-week period. SH not only reduced body weight but also corrected associated hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed to its specific effects on lipogenesis related genes (SREBP1a, FAS GAPT), and PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract ofS. herbacea has potential as a preventive agent for type 2 diabetes (and possibly hyperlipidemia) and deserves future clinical trial.

Antidiabetic stilbene and anthraquinone derivatives fromRheum undulatum

The antidiabetic-activity-guided fractionation and isolation of the 80% EtOH extracts obtained from cultivated Korean Rhubarb rhizomes (Rheum undulatum, Polygonaceae) led to the isolation and characterization of one stilbene, desoxyrhapontigenin (1) and two anthraquinones, emodin (2) and chrysophanol (3). Their structures were established by chemical and spectroscopic methods. Compounds1, 2 and3 inhibited postprandial hyperglycemia by 35.8, 29.5, 42.3%, respectively.

Antidiabetic coumarin and cyclitol compounds from Peucedanum japonicum.

The antidiabetic activity-guided fractionation and isolation of the 80% EtOH extracts from Peucedani Radix(Peucedanum japonicum, Umbelliferae) led to the isolation and characterization of a coumarin and a cyclitol as active principles, that is, peucedanol 7-O-β-D-glucopyranoside (1) and myo-inositol (2). Their structures were identified by spectroscopic methods. Compound1 showed 39% inhibition of postprandial hyperglycemia at 5.8 mg/kg dose, and compound2 also significantly inhibited postprandial hyperglycemia by 34% (P<0.05).

Anti-inflammation activity of Actinidia polygama

The fruit of Actinidia polygama (AP) has long been used as a folk medicine in Korea for treating pain, rheumatic arthritis and inflammation. The present investigation was carried out to determine thein vivo andin vitro anti-inflammatory activity of AP using several animal models of inflammation. The 70% ethanol extract of the fruit of AP significantly inhibited acetic acidinduced, vascular permeability in a dose dependent manner (23%, 38%, and 41% inhibition at doses of 200 mg/kg, 500 mg/kg and 1000 mg/kg, respectively). This effect was maintained in AP water-soluble fraction (APW). The APW fraction also showed significant inhibitory activity against the rat paw edema induced by a single treatment of carrageenan.In vitro experiments were performed to demonstrate the inhibitory activities of APW (100 μg/ml) on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. The results showed that APW dose-dependently suppressed LPS-induced NO production in RAW 264.7 macrophages without a notable cytotoxic effect and also decreased inducible NO synthase (iNOS) protein expression. APW also showed a significant inhibitory effect in LPS-induced PGE2 production and cyclooxygenase-2 (COX-2) expression.

In vivo and in vitro anti-inflammatory activities of alpha-linolenic acid isolated from Actinidia polygama fruits.

The fruit ofActinidia polygama (AP) has long been used as a folk medicine in Korea for the treatment of pain, rheumatoid arthritis and inflammation. In the present study, bioassay-guided fractionation of AP led to the separation and identification of a polyunsaturated fatty acid, α-linolenic acid (ALA), which was found to show anti-inflammatory activity. The anti-inflammatory effects of ALA, using acetic acid or carrageenan-induced inflammation models, were investigated in mice or rats, respectively. ALA significantly inhibited the acetic acid-induced vascular permeability in a dose dependent manner (34.2 and 37.7% inhibition at doses of 5 and 10 mg/ kg, respectively). ALA also significantly reduced a rat paw edema induced by a single treatment of carrageenan. To investigate the mechanism of the anti-inflammatory action of ALA, the effects of ALA on lipopolysaccharide (LPS)-induced responses in the murine macrophages cell line, RAW 264.7, were examined. Exposure of LPS-stimulated cells to ALA inhibited the accumulation of nitrite and prostaglandin E2 (PGE2) in the culture medium. Con-sistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 enzyme were markedly inhibited by ALA in a dose dependent manner. These results suggest that the anti-inflammatory activity of ALA might be due to the suppression of the expressions of iNOS and COX-2 mRNA.

Acanthopanax senticosus reverses fatty liver disease and hyperglycemia in ob/ob mice.

Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the progression of NAFLD to end-stage disease associated with the development of cirrhosis and liver disease. In a previous experiment, 50% ethanol extract ofAcanthopanax senticosus stem bark (ASSB) was found to reduce body weight and insulin resistance in high fat diet-induced hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB ethanol extract for an 8 week-period. ASSB ethanol extract reversed the hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB ethanol extract also specifically lowered circulating glucose and lipids, and enhanced insulin action in the liver. These changes culminated in inhibition of triglyceride synthesis in non-adipose tissues including liver and skeletal muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol extract is an effective treatment for insulin resistance and hepatic steatosis in ob/ob mice by decreasing hepatic lipid synthesis.

Vinegar- processed ginseng radix improves metabolic syndrome induced by a high fat diet in ICR mice

Ginseng has made a successful transition from the world of traditional tonic remedies to conventional medicine, and since the 1920s ginseng root has been documented to be effective in diabetes, hypertension, dyslipidemia and obesity. Based on this wide spectrum of activity we wondered whether ginseng root extract might also be effective in metabolic syndrome (MetSyn). In a series of investigations to develop a potential anti-MetSyn agent, we prepared a vinegar-processed form of ginseng radix (ginsam, GS) and compared its anti-MetSyn effects to those of non-processed ginseng radix (GR) in an ICR mouse model of MetSyn induced by a high fat diet. GR- and GS-treated mice (500 mg/kg/day for 8 weeks) had an 81% and 90% decrease in insulin resistance respectively, compared to the high fat diet (HFD) control. White adipocyte size was dramatically reduced by 67% and 80% in GR- and GS-treated groups respectively, compared to the HFD fed control. This result was reflected by a marked inhibition of weight gain in GS-treated mice (GR vs. GS, 53% vs. 86%). Analysis of ginsenoside composition indicated that prosapogenin Rg3 might be responsible for the anti-MetSyn activity of GS. In conclusion, Vinegar-processed ginseng radix (GS) was found to have a significantly greater anti-MetSyn effect than ginseng radix, and we suggest that ginsam should be subjected to clinical trials in the future, and that the role of prosapogenin Rg3 in the anti-MetSyn effect of ginsam should be confirmed.

AMP-activated protein kinase: a potential target for ginsenosides?

Panax ginseng is a best-selling medicinal plant showing an antidiabetic activity via human, animal and in vitro studies. Among bioactive constituents found in ginseng, ginsenosides are known to be responsible for antidiabetic activity of ginseng. Ginsenoside Rb2, one of the major ginsenosides found in Asian ginseng, is shown to inhibit palmitate-induced gluconeogenesis in H4IIE rat hepatocytes via AMP-activated protein kinase (AMPK)-induced up-regulation of orphan nuclear receptor small heterodimer partner (SHP). Up to now, about thirteen articles were published to demonstrate that the pharmacological or physiological activities of ginsenosides are associated with AMPK, and only protopanaxatriol-type ginsenosides such as Re, Rg1 and Rg2, have been shown to suppress the hepatic glucose production. Therefore, Rb2 is the first protopanaxadiol-type ginsenoside shown to inhibit hepatic gluconeogenesis through AMPK activation. Further work will reveal whether activation of AMPK pathway by Rb2 would be beneficial to diabetic animals or type 2 diabetic patients.