Clinical outcomes and the risk factors of coronary artery aneurysms that developed after drug-eluting stent implantation.

BACKGROUND: There is only limited data on coronary artery aneurysms (CAA) after drug-eluting stent (DES) implantation. METHODS AND RESULTS: Two hundred-fifty one patients who had 2 angiographic follow-ups at 8 months and 28-36 months, respectively, after the index procedure with DES from 2003 to 2007 were enrolled. A CAA was defined as a localized dilatation exceeding 1.5 times the diameter of the adjacent artery. The independent risk factors and major adverse cardiac events (MACE) were determined, including cardiac death, myocardial infarction (MI) and target-vessel revascularization (TVR), between the patients with CAA (n=35) and without them (n=216). On multivariate analysis, a lesion in an infarct-related artery (IRA) (odds ratio (OR): 6.1, P=0.001), a lesion in the left anterior descending artery (OR: 4.9, P=0.005), a lesion length >33 mm (OR: 3.9, P=0.022), and a lesion with chronic total occlusion (CTO) (OR: 3.4, P=0.044) were the independent risk factors for CAA. Follow-up duration was 1,046±516 days. Although most patients (71.4%) were asymptomatic, MACE was found in 10 patients (28.6%). No deaths occurred. MI with stent thrombosis occurred in 5 patients (14.3%) and TVR occurred in 10 patients (28.6%). CONCLUSIONS: The risk factors for the development of CAA after DES are a long lesion over 33 mm, a lesion in the left anterior descending artery, a lesion in an IRA, and CTO. Long-term follow-up and large clinical trials are warranted for patients with CAA.

The promotion of hair regrowth by topical application of a Perilla frutescens extract through increased cell viability and antagonism of testosterone and dihydrotestosterone.

This study investigated the potential hair regrowth effects associated with a plant extract of Perilla frutescens, which was selected due to its putative hair regrowth activity. Extracts were prepared from dried P. frutescens suspended in distilled water, where the resultant aqueous suspension was fractionated sequentially using hexane, ethyl acetate, n-butanol, and distilled water. We observed that the n-butanol fraction resulted in the highest hair regrowth activity. The n-butanol soluble fraction of P. frutescens extract (BFPE) was further separated using AB-8 macroporous resin and silica gel chromatography to obtain rosmarinic acid (RA), which demonstrated effective hair growth regeneration potential. BFPE also showed in vivo anti-androgenic activity following the use of a hair growth assay in testosterone-sensitive male C57Bl/6NCrSlc mice. Furthermore, the effects of cell viability promotion were investigated following an in vitro analysis in primary hair follicle fibroblast cells (PHFCs) treated with RA. The results suggested that RA was the active compound in P. frutescens that triggers hair growth, and RA could be a potential therapeutic agent for the promotion of hair growth and prevention of androgenetic alopecia (AGA).

Effects of selected ginsenosides on phorbol ester-induced expression of cyclooxygenase-2 and activation of NF-kappaB and ERK1/2 in mouse skin.

Our previous studies have demonstrated that the methanol extract of heat-processed Panax ginseng C.A. Meyer exerts antioxidative, antiinflammatory, and anti-tumor-promoting effects. In the present study, we examined the antiinflammatory effects of several ginsenosides (Rb(1), Rc, Re, Rg(1), Rg(3)) derived from P. ginseng. Topical application of each of these ginsenosides significantly attenuated ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). These ginsenosides also suppressed expression of cyclooxygenase-2 (COX-2) and activation of NF-kappaB in the TPA-treated dorsal skin of mice. Of the ginsenosides tested, Rg(3) was found to be most effective in terms of inhibiting TPA-induced ear edema, COX-2 expression, and NF-kappaB activation.

Protective effect of ginseng extract against apoptotic cell death induced by 2,2',5,5'-tetrachlorobiphenyl in neuronal SK-N-MC cells.

Oxidative stress plays an important role in the pathological processes of neurodegenerative diseases. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) induces apoptotic death in human neuronal SK-N-MC cells, as demonstrated by gel electrophoresis, which demonstrates the proteolytic cleavage of beta-catenin and poly(ADP-ribose) polymerase (PARP) and the characteristic ladder patterns of DNA fragmentation. In the present study, we investigated whether Panax ginseng extract protect human neuronal SK-N-MC cells from PCB 52-induced apoptosis. The addition of 500 microg/ml of ginseng extract to a culture medium significantly protected neuronal cell from the apoptosis mediated by PCB 52 and remarkably attenuated lipid peroxidation, the generation of reactive oxygen species, and DNA fragmentation, and markedly reduced the PCB 52 induced proteolytic cleavage of beta-catenin and PARP. These results show that Panax ginseng extract protects human neuronal SK-N-MC cells from the apoptosis induced by PCB 52. We suggest that Panax ginseng extracts may protect neuronal cells from oxidative injury.

Effects of ginsenosides Rg3 and Rh2 on the proliferation of prostate cancer cells.

Ginseng has an anti-cancer effect in several cancer models. This study was to characterize active constituents of ginseng and their effects on proliferation of prostate cancer cell lines, LNCaP and PC3. Cell proliferation was measured by [3H]thymidine incorporation, the intracellular calcium concentration by a dual-wavelength spectrophotometer system, effects on mitogen-activated protein (MAP) kinases by Western blotting, and cell attachment and morphologic changes were observed under a microscope. Among 11 ginsenosides tested, ginsenosides Rg3 and Rh2 inhibited the proliferation of prostate cancer cells. EC50s of Rg3 and Rh2 on PC3 cells were 8.4 microM and 5.5 microM, respectively, and 14.1 microM and 4.4 microM on LNCaP cells, respectively. Both ginsenosides induced cell detachment and modulated three modules of MAP kinases activities differently in LNCaP and PC3 cells. These results suggest that ginsenosides Rg3 and Rh2-induced cell detachment and inhibition of the proliferation of prostate cancer cells may be associated with modulation of three modules of MAP kinases.

Anti-obesity effects of black ginseng extract in high fat diet-fed mice.

Black ginseng is produced by a repeated steaming process. The aim of this study was to investigate the anti-obesity effects of black ginseng ethanol extract (BG-EE) in high fat (HF) diet-fed mice. Two groups were fed either a normal control (NC) diet or a HF diet (45% kcal fat). The other three groups were given a HF diet supplemented with 1% BG-EE, 3% BG-EE, and 5% BG-EE for 12 wk. The anti-obesity effects of the BG-EE supplement on body weight, the development of fat mass, and lipid mechanisms were assessed in obese mice. HF-induced hyperlipidemia, fat accumulation in the liver, and white adipose tissues were reduced after BG-EE supplementation. Total fecal weight and the amount of fecal fat excretion also were increased after BG-EE supplementation. These results suggest that BG-EE may be useful to ameliorate HF-induced obesity through the strong inhibition of fat digestion.

Marked production of ginsenosides Rd, F2, Rg3, and compound K by enzymatic method.

The hydrolysis of protopanaxadiol-type saponin mixture by various glycoside hydrolases was examined. Among these enzymes, crude preparations of lactase from Aspergillus oryzae, beta-galactosidase from A. oryzae, and cellulase from Trichoderma viride were found to produce ginsenoside F(2) [3-O-(beta-D-glucopyranosyl)-20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], compound K [20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol], and ginsenoside Rd {3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol}, respectively, from protopanaxadiol-type saponin mixture in large quantities. Moreover, the crude preparation of lactase from Penicillium sp. having a high producing activity of ginsenoside Rh(1) (6-O-beta-D-glucopyranosyl-20(S)-protopanaxatriol) from protopanaxatriol-type saponin mixture gave ginsenoside Rd as a main product, ginsenoside Rg(3) {3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]-20(S)-protopanaxadiol}, and compound K from protopanaxadiol-type saponin mixture. The hydrolytic pathways of ginsenosides Rb(1), Rb(2), and Rc to ginsenosides Rd, Rg(3), and F(2), and compound K by crude preparations of four glycoside hydrolases were also studied. This is the first report on the enzymatic preparation of an intestinal bacterial metabolite, ginsenoside F(2), in quantity, and a considerable amount of a minor saponin, ginsenoside Rg(3), from a protopanaxadiol-type saponin mixture.

Korea red ginseng water extract increases nitric oxide concentrations in exhaled breath.

Panax ginseng is well known to enhance the release of nitric oxide (NO) from endothelial cells of the rat aorta and to reduce blood pressure in animals. In this study, we investigated the effects of water extract of Korea red ginseng (KRG) on NO concentration levels in the exhaled breath, blood pressure, and heart rate of human volunteers. We also are interested in whether NO levels in exhaled breath are increased by KRG extract, and correlated with blood pressure and heart rate. Twelve healthy, non-smoking male volunteers were recruited for this study. A single administration of KRG water extract (500 mg/50 kg) increased NO levels in exhaled breath, and concomitantly decreased mean blood pressure and heart rate. The correlation value between NO levels and heart rate (r = 0.94), and the correlation value between NO levels and heart rate (r = 0.84) are significant (P < 0.01). Linear regression analysis shows the clear conversed correlation between NO levels and blood pressure as well as heart rate. Therefore, present data suggest that KRG may be useful for the treatment of hypertension and pulmonary vascular obstruction.

Enzymatic preparation of ginsenosides Rg2, Rh1, and F1.

During investigation of the hydrolysis of a protopanaxatriol-type saponin mixture by various glycoside hydrolases, crude preparations of beta-galactosidase from Aspergillus oryzae and lactase from Penicillium sp. were found to produce two minor saponins, ginsenoside Rg(2) [6-O-(alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl)-20(S)-protopanaxatriol] and ginsenoside Rh(1) (6-O-beta-D-glucopyranosyl-20(S)-protopanaxatriol), respectively, in high yields. Moreover, a naringinase preparation from Penicillium decumbens readily gave an intestinal bacterial metabolite, ginsenoside F(1) (20-O-beta-D-glucopyranosyl-20(S)-protopanaxatriol), as the main product, with a small amount of 20(S)-protopanaxatriol from a protopanaxatriol-type saponin mixture. Also, a hesperidinase from Penicillium sp. selectively hydrolyzed ginsenoside Re into ginsenoside Rg(1). This is the first report on the enzymatic preparation of minor saponins, ginsenosides Rg(2) and Rh(1), and of an intestinal bacterial metabolite, ginsenoside F(1), with high efficiency from a protopanaxatriol-type saponin mixture.

Enzymatic preparation of ginsenosides Rg2, Rh1, and F1 from protopanaxatriol-type ginseng saponin mixture.

During investigations on the hydrolysis of a protopanaxatriol-type saponin mixture by various glycoside hydrolases, it was found that two minor saponins, ginsenosides Rg 2 and Rh 1, were formed in high yields by crude beta-galactosidase from Aspergillus oryzae and crude lactase from Penicillium sp., respectively. Moreover, a crude preparation of naringinase from Penicillium decumbens readily hydrolyzed a protopanaxatriol-type saponin mixture to give an intestinal bacterial metabolite, ginsenoside F 1 as the main product. A crude preparation of hesperidinase from Penicillium sp. selectively hydrolyzed ginsenoside Re into ginsenoside Rg 1. This is the first report on the enzymatic preparation of minor saponins, ginsenosides Rg 2 and Rh 1, and of an intestinal bacterial metabolite, ginsenoside F 1, with a high efficiency from a protopanaxatriol-type saponin mixture.