Wan Gi Kim

Gene-polymorphisms of angiotensin converting enzyme and endothelial nitric oxide synthase in patients with erectile dysfunction.

Aims of the study: Regulation of the penile smooth muscle tone and contractility is closely related to the activity of vasoactive substances, angiotensin II or nitric oxide. We investigated the relationship between gene polymorphism in the angiotensin converting enzyme (ACE) or endothelial nitric oxide synthase (ecNOS) and development of erectile dysfunction.Methods: In 84 subjects with organic erectile dysfunction and 63 control subjects, gene polymorphisms in the ACE and ecNOS were determined by the polymerase chain reaction (PCR).Results: The DD genotype of ACE was significantly (P<0.01) more frequent in subjects with organic erectile dysfunction (54%) than in control subjects (24%). There was no significant difference in the distribution of the genotypes of ecNOS.Conclusion: The deletion polymorphism in the ACE gene, the DD genotype, as a marker of general vascular disease, may be seen more frequently in men with a diagnosis of vasculogenic erectile dysfunction.

Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: a multicenter, placebo-controlled, double-blind clinical study.

Ginseng is beneficial for many aspects of human physiology, including sexual function. In this study, we have evaluated the efficacy and safety of an extract of ginseng berry, which has a ginsenoside profile distinct from other parts of the plant, on sexual function in men with erectile dysfunction. In all, 119 men with mild-to-moderate ED participated in a multicenter, randomized, double-blind, parallel, placebo-controlled clinical study. They were administered 4 tablets of either standardized Korean ginseng berry (SKGB, 350 mg ginseng berry extract per tablet), or placebo, daily, for 8 weeks. Efficacy was assessed with the International Index of Erectile Function (IIEF)-15 and premature ejaculation diagnostic tool (PEDT) at the end of the 4th and 8th week. We observed that the total and each of the individual domain scores of IIEF-15 increased from 40.95±7.05 to 46.19±12.69 significantly in the SKGB by the 8th week (P<0.05). The erectile function domain of IIEF changed slightly from 17.17±2.57 to 18.59±5.99 in the SKGB group by the 8th week (P<0.05). In addition, PEDT scores significantly improved from 9.14±4.57 to 7.97±4.4 and 7.53±4.26 in the SKGB group after 4 and 8 weeks of treatment (P<0.05). Safety markers including hormone and lipid in the blood were assessed at the end of the 4th and 8th week and they remained unchanged. Oral administration of the SKGB extract improved all domains of sexual function. It can be used as an alternative medicine to improve sexual life in men with sexual dysfunction.

Ginseng Berry Extract Prevents Atherogenesis via Anti-Inflammatory Action by Upregulating Phase II Gene Expression

Ginseng berry possesses higher ginsenoside content than its root, which has been traditionally used in herbal medicine for many human diseases, including atherosclerosis. We here examined the antiatherogenic effects of the Korean ginseng berry extract (KGBE) and investigated its underlying mechanism of action in vitro and in vivo. Administration of KGBE decreased atherosclerotic lesions, which was inversely correlated with the expression levels of phase II genes to include heme oxygenase-1 (HO-1) and glutamine-cysteine ligase (GCL). Furthermore, KGBE administration suppressed NF-κB-mediated expression of atherogenic inflammatory genes (TNF-α, IL-1β, iNOS, COX-2, ICAM-1, and VCAM-1), without altering serum cholesterol levels, in ApoE−/− mice fed a high fat-diet. Treatment with KGBE increased phase II gene expression and suppressed lipopolysaccharide-induced reactive oxygen species production, NF-κB activation, and inflammatory gene expression in primary macrophages. Importantly, these cellular events were blocked by selective inhibitors of HO-1 and GCL. In addition, these inhibitors reversed the suppressive effect of KGBE on TNF-α-mediated induction of ICAM-1 and VCAM-1, resulting in decreased interaction between endothelial cells and monocytes. These results suggest that KGBE ameliorates atherosclerosis by inhibiting NF-κB-mediated expression of atherogenic genes via upregulation of phase II enzymes and thus has therapeutic or preventive potential for atherosclerosis.

Effects of Korean ginseng berry extract (GB0710) on penile erection: evidence from in vitro and in vivo studies

Several reports have promoted the root-derived Korean red ginseng (KRG; Panax ginseng) as alternative treatment for erectile dysfunction (ED), and ginsenosides are known to be the principal active ingredients of ginseng. Recent studies showed that ginseng berries produce more ginsenosides than KRG; thus, we investigated the ability of the Korean ginseng berry extract GB0710 to relax the penile corpus cavernosum smooth muscle (CCSM) in this study. As a comparative control, the results were compared to those obtained using KRG. In addition, possible mechanisms of action for GB0710 were investigated. While KRG and GB0710 both displayed dose-dependent relaxation effects on precontracted rabbit CCSM in vitro, GB0710 was shown to be more potent than KRG. The GB0710-induced relaxation could be partially reduced by removing the endothelium. In addition, pre-treatment with several nitric oxide (NO) inhibitors significantly inhibited the relaxation of muscle strips. Furthermore, administration of GB0710 increased intracavernosal pressure (ICP) in a rat in vivo model in both a dose- and duration-dependent manner. Intracellular NO production in human microvascular endothelial cells could be induced by GB0710 and inhibited by N(G)-monomethyl-L-arginine. In conclusion, GB0710 had a greater relaxation effect on rabbit CCSM than did KRG extract, and increased ICP in a rat model in both a dose- and a duration-dependent manner. This relaxing effect might be mediated by NO production.

Chitooligosaccharide Induces Mitochondrial Biogenesis and Increases Exercise Endurance through the Activation of Sirt1 and AMPK in Rats

By catabolizing glucose and lipids, mitochondria produce ATPs to meet energy demands. When the number and activity of mitochondria are not sufficient, the human body becomes easily fatigued due to the lack of ATP, thus the control of the quantity and function of mitochondria is important to optimize energy balance. By increasing mitochondrial capacity? it may be possible to enhance energy metabolism and improve exercise endurance. Here, through the screening of various functional food ingredients, we found that chitooligosaccharide (COS) is an effective inducer of mitochondrial biogenesis. In rodents, COS increased the mitochondrial content in skeletal muscle and enhanced exercise endurance. In cultured myocytes, the expression of major regulators of mitochondrial biogenesis and key components of mitochondrial electron transfer chain was increased upon COS treatment. COS-mediated induction of mitochondrial biogenesis was achieved in part by the activation of silent information regulator two ortholog 1 (Sirt1) and AMP-activated protein kinase (AMPK). Taken together, our data suggest that COS could act as an exercise mimetic by inducing mitochondrial biogenesis and enhancing exercise endurance through the activation of Sirt1 and AMPK.

An Ethanol Extract of Artemisia iwayomogi Activates PPARδ Leading to Activation of Fatty Acid Oxidation in Skeletal Muscle

Although Artemisia iwayomogi (AI) has been shown to improve the lipid metabolism, its mode of action is poorly understood. In this study, a 95% ethanol extract of AI (95EEAI) was identified as a potent ligand of peroxisome proliferator-activated receptorδ (PPARδ) using ligand binding analysis and cell-based reporter assay. In cultured primary human skeletal muscle cells, treatment of 95EEAI increased expression of two important PPARδ-regulated genes, carnitine palmitoyl-transferase-1 (CPT1) and pyruvate dehydrogenase kinase isozyme 4 (PDK4), and several genes acting in lipid efflux and energy expenditure. Furthermore, 95EEAI stimulated fatty acid oxidation in a PPARδ-dependent manner. High-fat diet-induced obese mice model further indicated that administration of 95EEAI attenuated diet-induced obesity through the activation of fatty acid oxidation in skeletal muscle. These results suggest that a 95% ethanol extract of AI may have a role as a new functional food material for the prevention and/or treatment of hyperlipidermia and obesity.

Separation of Polyphenols and Caffeine from the Acetone Extract of Fermented Tea Leaves (Camellia sinensis) Using High-Performance Countercurrent Chromatography

Leaves from Camellia sienensis are a popular natural source of various beverage worldwide, and contain caffeine and polyphenols derived from catechin analogues. In the current study, caffeine (CAF, 1) and three tea polyphenols including (−)-epigallocatechin 3-O-gallate (EGCg, 2), (−)-gallocatechin 3-O-gallate (GCg, 3), and (−)-epicatechin 3-O-gallate (ECg, 4) were isolated and purified by flow-rate gradient high-performance countercurrent chromatography (HPCCC) using a two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (1:9:1:9, v/v). Two hundred milligrams of acetone-soluble extract from fermented C. sinensis leaves was separated by HPCCC to give 1 (25.4 mg), 2 (16.3 mg), 3 (11.1 mg) and 4 (4.4 mg) with purities over 98%. The structures of 1–4 were elucidated by QTOF-MS, as well as 1H- and 13C-NMR, and the obtained data were compared to the previously reported values.

Mild Mitochondrial Uncoupling Prevents Premature Senescence in Human Dermal Fibroblasts

TO THE EDITOR Mitochondrial uncoupling, an increased permeability of the inner membrane to protons not coupled to ATP synthesis, dissipates mitochondrial membrane potential. Mild mitochondrial uncoupling is believed to prolong lifespan of certain model organisms by reducing the production of reactive oxygen species (ROS) and preventing oxidant damage (Brand, 2000). Indeed, long-lived Caenorhabditis elegans strains have a lower membrane potential compared with wild-type strains (Lemire et al., 2009). Overexpression of the uncoupling protein UCP1 in murine skeletal muscle offers protection from age-related damage and disease (Gates et al., 2007). In addition, uncouplers extend the lifespan of yeast (Longo et al., 1999) and mice (Caldeira da Silva et al., 2008), suggesting that mild mitochondrial uncoupling might mitigate at least some deleterious aspects of aging. However, little is known about the effect of mitochondrial uncoupling on the aging of human skin. In this current study, we investigated the protective effect of mild mitochondrial uncoupling against oxidative stressinduced premature senescence in human dermal fibroblasts (HDFs). Oxidative stress is a pivotal mechanism leading to skin aging (Masaki, 2010). Accumulation of ROS elicits premature cellular senescence and deleterious alteration of collagen homeostasis, which can contribute to the development of characteristics of aged skin such as coarse, rough, and wrinkled appearance (Varani et al., 2006; Velarde et al., 2012). HDFs undergo cellular senescence by addition of 200mM H2O2 for 2 hours and prolonged subculture (Chen and Ames, 1994; Ido et al., 2012), which can be detected by changes in cellular morphology and senescence-associated b-galactosidase (SA-bgal) staining at 12 days after addition of H2O2 (Figure 1a). In order to determine whether mild mitochondrial uncoupling could inhibit oxidative stress–induced premature senescence, we pretreated HDFs with 60 nM carbonyl cyanide (P-trifluoromethoxy)-phenylhydrazone (FCCP) for 30 minutes before addition of H2O2. In a pilot study, the effective concentration of FCCP that would reduce the ROS production and mitochondrial membrane potential but have no discernible effect on cell viability was determined (Supplementary Figures S1 and S2 online). We found that cells pretreated with FCCP showed delayed senescence (Figure 1a), increased proliferative capacity (Figure 1b), reduced levels of oxidants (Figure 1c), and decreased expression levels of senescence-associated molecular markers, p21 and p16 (Figure 1d), compared with untreated senescent HDFs. Next, we investigated the uncoupling effect triggered by FCCP on collagen homeostasis in premature senescent HDFs. Aberrant collagen homeostasis, a prominent feature of aged human skin, Accepted article preview online 20 August 2013; published online 19 September 2013 Abbreviations: FCCP, carbonyl cyanide (p-trifluoromethoxy)-phenylhydrazone; HDF, human dermal fibroblasts; JNK, c-Jun N-terminal kinases; MMP-1, Matrix metalloproteinase-1; SA-bgal, senescenceassociated b-galactosidase SY Cho et al. Critical Role of Mitochondrial Uncoupling in Aging of Human Skin

Effects of Chitooligosaccharide Lactate Salt on Activity of Acetaldehyde Dehydrogenase

Chitooligosaccharides (COS), a kind of oligosaccharide made from chitin or chitosan, have been used a popular remedy for hangovers. In this study we investigated the in vitro effect of COS lactate salt on ethanol-induced cytotoxicity and the in vivo effect of short-term COS lactate salt feeding on ethanol-induced hangover. Pretreatment of HepG2 cells with COS lactate salt significantly reduced ethanol-induced cytotoxicity and suppressed generation of reactive oxygen species. In addition, COS lactate salt dose-dependently increased acetaldehyde dehydrogenase (ALDH) activity in vitro and reversed the ALDH inhibition induced by daidzin. Furthermore, oral administration of COS lactate salt (200 mg/kg) for 5 days significantly decreased the blood levels of alcohol and acetaldehyde in ethanol-treated mice. It was also demonstrated that hepatic mitochondrial ALDH activity was significantly increased in COS lactate salt-treated mice. Taken together, these findings indicate that COS lactate salt may have efficacy for the management of alcoholic hangovers.