Sung Kwon Ko

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.

Ginsenoside Re Rescues Methamphetamine-Induced Oxidative Damage, Mitochondrial Dysfunction, Microglial Activation, and Dopaminergic Degeneration by Inhibiting the Protein Kinase Cδ Gene

Ginsenoside Re, one of the main constituents of Panax ginseng, possesses novel antioxidant and anti-inflammatory properties. However, the pharmacological mechanism of ginsenoside Re in dopaminergic degeneration remains elusive. We suggested that protein kinase C (PKC) δ mediates methamphetamine (MA)-induced dopaminergic toxicity. Treatment with ginsenoside Re significantly attenuated methamphetamine-induced dopaminergic degeneration in vivo by inhibiting impaired enzymatic antioxidant systems, mitochondrial oxidative stress, mitochondrial translocation of protein kinase Cδ, mitochondrial dysfunction, pro-inflammatory microglial activation, and apoptosis. These protective effects were comparable to those observed with genetic inhibition of PKCδ in PKCδ knockout (−/−) mice and with PKCδ antisense oligonucleotides, and ginsenoside Re did not provide any additional protective effects in the presence of PKCδ inhibition. Our results suggest that PKCδ is a critical target for ginsenoside Re-mediated protective activity in response to dopaminergic degeneration induced by MA.

Anti-platelet aggregation activity of stilbene derivatives fromRheum undulatum

In continued studies on cultivated Korean rhubarb rhizomes (Rheum undulatum), three known stilbenes (desoxyrhapontigenin, rhapontigenin, piceatannol) have been screened for activity on blood platelet aggregation. Both rhapontigenin and desoxyrhapontigenin exhibited strong inhibition on the aggregation induced by arachidonic acid and collagen. However, piceatannol did not show inhibition. These inhibitory effects may partially contribute to antiblood stagnancy activity of rhubarb.

Quercetin-3-O-β-d-glucuronopyranoside (QGC)-induced HO-1 expression through ERK and PI3K activation in cultured feline esophageal epithelial cells

Heme oxygenase-1 (HO-1) is one of the antioxidant enzymes which help protect against cellular damage. The present study examined the ability of Quercetin-3-O-beta-D-glucuronopyranoside (QGC), flavonoid glucoside extracted from Rumex Aquaticus Herba, to induce expression of HO-1 and analyzed its signaling mechanism in cultured feline esophageal epithelial cells (EEC). Culture of the esophageal epithelial cells from cat was prepared. The data suggested that QGC could result in enhanced antioxidant enzyme defense system via HO-1 expression and Nrf2 translocation involving both the ERK and PI3K-Akt pathways as well as partly PKC pathways in EEC.

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.

Changes in the Contents of Prosapogenin in the Red Ginseng (Panax ginseng) Depending on Steaming Batches

This study compared the contents of ginsenosides depending on steaming conditions of red ginsengs to provide basic information for developing functional foods using red ginsengs. The red ginseng steamed eight times at 98℃ ranked atop the amounts of prosapogenins ever detected in red ginsengs (ginsenoside Rg2, Rg3, Rg5, Rg6, Rh1, Rh4, Rk1, Rk3, F1, F4, 1.15%) among red ginsengs steamed more than twice. When steamed eight times at 98℃, 2.7 times as much prosapogenins such as ginsenosides Rg2, Rg3, Rg5, Rg6, Rh1, Rh4, Rk1, Rk3, F1, and F4 as those steamed just once at 98℃ was collected. In addition, the red ginsengs steamed eight times at 98℃ contained more amounting ginsenoside Rg3 (0.28%) than that in the red ginseng steamed several times at random. Accordingly, it is recommendable that red ginsengs steamed 8 times, which proved to be the optimal steaming condition, be used rather than those steamed 9 times (black ginsengs), in order to develop red ginseng products of high prosapogenin concentration and high functions.

Ginsenoside Re protects methamphetamine-induced mitochondrial burdens and proapoptosis via genetic inhibition of protein kinase C δ in human neuroblastoma dopaminergic SH-SY5Y cell lines.

Recently, we have demonstrated that ginsenoside Re protects methamphetamine (MA)‐induced dopaminergic toxicity in mice via genetic inhibition of PKCδ and attenuation of mitochondrial stress. In addition, we have reported that induction of mitochondrial glutathione peroxidase (GPx) is also important for neuroprotection mediated by ginsenoside Re. To extend our knowledge, we examined the effects of ginsenoside Re against MA toxicity in vitro condition using SH‐SY5Y neuroblastoma cells. Treatment with ginsenoside Re resulted in significant attenuations against a decrease in the activity of GPx and an increase in the activity of superoxide dismutase (SOD) in the cytosolic and mitochondrial fraction. The changes in glutathione (GSH) paralleled those in GPx in the same experimental condition. Consistently, ginsenoside Re treatment exhibited significant protections against cytosolic and mitochondrial oxidative damage (i.e. lipid peroxidation and protein oxidation), mitochondrial translocation of PKCδ, mitochondrial dysfunction (mitochondrial transmembrane potential and intra‐mitochondrial Ca2+), apoptotic events [i.e., cytochrome c release from mitochondria, cleavage of caspase‐3 and poly(ADP‐ribose)polymerase‐1, nuclear condensation, terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL)‐positive apoptotic cells], and a reduction in the tyrosine hydroxylase (TH) expression and TH activity induced by MA in SH‐SY5Y neuroblastoma cells. These protective effects of ginsenoside Re were comparable to those of PKCδ antisense oligonucleotide (ASO). However, ginsenoside Re did not significantly provide additional protective effects mediated by genetic inhibition of PKCδ. Our results suggest that PKCδ is a specific target for ginsenoside Re‐mediated protective activity against MA toxicity in SH‐SY5Y neuroblastoma cells. Copyright

Antioxidant Activities of Ginseng Seeds Treated by Autoclaving

Ginseng seeds were treated with different autoclaving temperatures and autoclaving times, and extracted with 80% methanol to measure changes in antioxidant activity. The antioxidant activity of ginseng seeds treated by autoclaving was measured by 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, 2,2’-aziono-bis(3-ethylbenzthiazoline)-6-sulfonic acid radical scavenging activity, superoxide dismutase SOD-like activity, ferric reducing antioxidant power (FRAP), and total phenolic compound content. As autoclaving temperature and time were increased, the L lightness value decreased and the redness value tended to increase. Total phenolic compound content was about three times higher in ginseng seeds treated with autoclaving at 130℃ than in ginseng seeds that were not treated. DPPH radical scavenging activity and ABTS radical scavenging activity increased as autoclaving temperature and time were increased. In particular, when the concentration was 100 ppm, the ABTS radical scavenging activity was 91.80% in ginseng seeds treated by autoclaving at 130℃, which was the highest antioxidant activity. FRAP and SOD-like antioxidant activity tended to increase significantly as autoclaving temperature and time were increased.

Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80). Ginsenoside Re (20 mg/kg or 100 mg/kg) was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration) and xanthine oxidase (XO) and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation) and decreases in the contents of hexosamine (a marker of gastric mucus) and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue.

A new stilbene diglycoside fromRheum undulatum

A new stilbene diglycoside, piceatannol-3, 4′-O-β-D-diglucopyranoside (I), together with desoxyrhaponticin (II), emodin-1-O-β-D-glucopyranoside (III), and physcion-8-O-b-D-glucopyranoside (IV), were isolated from the rhizomes of cultivated Korean rhubarb rhizomes (Rheum undulatum), Jong DaeWhang, and the structures of I–IV were identified on the basis of chemical and spectral evidences.