YES-10 Improves Stress, Tension, and Fatigue by Reducing Cortisol and IL-6 Levels.

The extract of Clematis mandshurica Rupr. (CMR) inhibits the production of proinflammatory mediators from lipopolysaccharide-stimulated peritoneal macrophages and concanavalin A-stimulated splenocytes. Erigeron annuus Pers. (EAP) extract suppresses the production of reactive oxygen species (ROS) from preadipocytes. Furthermore, the mixture of the leaf extracts of CMR and EAP, YES-10®, protected against nerve injuries induced by ischemia/reperfusion, suggesting a ROS-scavenging action. These observations show the anti-inflammatory action of YES-10. Inflammatory cytokines can cause alterations in mental function, including depression, by influencing the neurotransmitter system. Thus, it was hypothesized that YES-10 could improve mental health, such as depression, anxiety, and sense of well-being. Seventy-two subjects were recruited and randomly divided into YES-10 or placebo groups (n = 36 per group). Each group was daily administered two capsules orally, containing 200 mg of YES-10 or placebo, for 4 weeks in a double-blinded manner and tested for levels of depression, anxiety, well-being, and mental fitness using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Psychosocial Well-being Index (PWI), and Mental Fitness Scale (MFS). In addition, the levels of cortisol (a stress hormone), interleukin-6 (IL-6) (an inflammatory cytokine), and 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative stress) in the serum were measured. The BDI, BAI, PWI, and MFS scores decreased significantly, and the serum levels of cortisol, IL-6, and 8-OHdG were lowered significantly (P < .05), suggesting that YES-10 has the ability to improve mental health by relieving stress and by decreasing inflammation and oxidative stress.

Comparison of therapeutic effects between topical 8-oxo-2'-deoxyguanosine and corticosteroid in ocular alkali burn model.

We compared the therapeutic effects of topical 8-oxo-2'-deoxyguanosine (8-oxo-dG) and corticosteroid in a murine ocular alkali burn model. (n = 128) The corneal alkali burn model was established by applying 0.1 N sodium hydroxide (NaOH), followed by treatment with 8-oxo-dG, 0.1% fluorometholone (FML), 1% prednisolone acetate (PDE), or phosphate-buffered saline (PBS) twice daily. One week later, the clinical and histological status of the cornea were assessed. Transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well as the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the cornea, were assayed. The 8-oxo-dG and PDE groups showed marked improvements in corneal integrity and clarity when compared with the PBS group (each p < 0.01). The numbers of cells stained for neutrophil elastase and F4/80-positive inflammatory cells were significantly decreased, with levels of interleukin(IL)-1ß, IL-6, tumor necrosis factor(TNF)-α, and total ROS/RNS amounts markedly reduced in the 8-oxo-dG, FML, and PDE groups (each p < 0.05). Levels of NADPH oxidase type 2 and 4 were substantially more repressed in the 8-oxo-dG-treated group than in the PDE-treated group (each p < 0.05). Topical 8-oxo-dG showed excellent therapeutic effects that were comparable with those treated with topical PDE in a murine ocular alkali burn model.

Anti-dermatitis effects of oak wood vinegar on the DNCB-induced contact hypersensitivity via STAT3 suppression.

AIMS OF THE STUDY: The aim of this study was to evaluate the anti-dermatitis effects of oak wood vinegar (OWV) in a 2,4-dinitrochlorobenzene (DNCB)-induced contact dermatitis mice model. MATERIALS AND METHODS: Immunoglobulin E (IgE) production, infiltration of immune cells (neutrophils, CD3+ cells), inducible nitric oxide synthase (iNOS) expression, skin thickness, and expression of phosphorylated STAT3 (signal transducers and activators of transcription 3) protein were tested in a DNCB-induced contact dermatitis model. In vitro wound healing and proliferative assays were also performed. RESULTS: OWV showed anti-inflammatory effects on DNCB-induced dermatitis in mice, leading to inhibition of IgE production, immune cell infiltration, and iNOS expression. Skin thickness and the level of phospho-STAT3 were dramatically reduced by OWV. Using the HaCaT human keratinocyte cell line, we confirmed that constitutive STAT3 activation induced faster proliferation of epithelial cells. In addition, OWV suppressed HaCaT proliferative ability and phospho-STAT3 levels. CONCLUSIONS: The study revealed that OWV has anti-inflammatory and anti-proliferative effects in a DNCB-induced contact dermatitis mice model. Furthermore, we showed that the mechanism by which OWV most likely inhibits epithelial proliferation is through STAT3 inactivation.

Inhibition of Rac and Rac-linked functions by 8-oxo-2'-deoxyguanosine in murine macrophages.

Rac is a protein involved in the various functions of macrophages (Mphi), including the production of reactive oxygen species (ROS), phagocytosis, chemotaxis and the secretion of cytokines (such as gamma-INF). This study tested the effects of nucleosides containing 8-oxoguanine(8-hydroxyguanine) such as 8-oxo-2'-guanosine (8-oxoG) or 8-oxo-2'-deoxyguanosine (8-oxodG), on Rac and the above-listed Rac-associated functions of Mphi using mouse peritoneal Mphi (MpMphi). It is reported that 8-oxodG was able to effectively inhibit Rac and the Rac-associated functions of MpMphi. Compared to 8-oxodG, 8-oxoG showed negligible effects. Furthermore, normal nucleosides such as deoxyguanosine (dG), guanosine (G) and adenosine (A) did not exert any effects. These results suggest that 8-oxodG could be used as a potential tool to modulate the functions of Mphi that are intimately related to various pathological processes.

Comparison of anti-oxidant activities of seventy herbs that have been used in Korean traditional medicine.

Many herbs have been used as therapeutics in Korean traditional medicine. In view of their clinical indications, anti-oxidant activity may contribute to their pharmacological effects. However, anti-oxidant information on these plants has not been available. In this study, seventy herbs which have been used in Korean traditional medicine were selected and screened for anti-oxidant activity using their water extracts. The anti-oxidant activity was assessed by their ability to inhibit three oxidation reactions; luminol/Fenton reagent, 2, 7-dichlorodihydrofluorescein (DCHF)/Fenton reagent and DCHF/peroxynitrite. In each assay, 70 herbs were divided into two groups; anti-oxidant group which inhibited the respective oxidation reaction and was majority (about 60 herbs), and pro-oxidant group which enhanced the oxidation reaction but was minority (more or less 10 herbs). When the herbs were listed in the order of their anti-oxidant strength, the orders obtained from each assay were found to be quite similar. The upper top rankers (more or less 10 herbs) in each assay showed strong activity compared to the others. The uppermost rankers in each assay were Rubus coreanus Miquel/ Rubus schizostylus, Schisandra chinensis Baillon/ Schizandra chinensis and Terminalia chebula Retzius/ Terminalia chebula. Of the pro-oxidant herbs, about 4-5 herbs were strongly pro-oxidant, which enhanced the control oxidation reactions to 150-300%. But the meaning of this observation is not known since few of them in one assay were also anti-oxidant in other assays. The results obtained in the present study may serve as information for understanding pharmacological effects of these herbs and developing new drugs from them.

Polyvinyl alcohol embolization adjuvant to oily chemoembolization in advanced hepatocellular carcinoma with arterioportal shunts.

OBJECTIVE: To assess the feasibility and safety of polyvinyl alcohol (PVA) embolization adjuvant to transarterial oily chemoembolization (P-TACE) in advanced hepatocellular carcinoma (HCC) with arterioportal shunts (APS). MATERIALS AND METHODS: Nineteen patients who underwent PVA embolization for APS before a routine chemoembolization (TACE) procedure were retrospectively reviewed. 10 of these 19 patients underwent follow-up TACE or P-TACE after P-TACE (Group A), but nine patients underwent only initial P-TACE because of progression of HCC and/or underlying liver cirrhosis (Group B). Hepatic function tests, APS grades, and portal flow directions were evaluated before and after P-TACE sessions. Complications after procedures and survival days were also evaluated. RESULTS: In group A, APS grade was improved in eight patients and five of six patients with hepatofugal flow showed restored hepatopetal flow postoperatively. No immediate complication was developed in either group. Transient hepatic insufficiency developed in eight (42.1%) of 19 patients after P-TACE, and seven (87.5%) of these eight recovered within two weeks under conservative care. The mean and median survival time all study subjects was 280 days and 162 days. CONCLUSION: P-TACE is feasible and safe in advanced HCC patients with APS.

Comparison of the antioxidant activities of nine different fruits in human plasma.

Oxidative stress in humans is associated with damage to DNA, proteins, and biological membranes. Oxidative stress, which often arises as a result of an imbalance in the human antioxidant status, has been implicated in aging and a number of human diseases such as cancer, atherosclerosis, and rheumatoid arthritis. This study was performed to test the hypothesis that the consumption of fruit juices may improve antioxidant status in human plasma. Ten healthy men 25-26 years old were recruited for the study. After overnight fasting, study subjects were fed 150 mL of fruit juice, and blood was collected at 0, 30, 60, 90, and 120 minutes after consumption. After a 1-day wash-out period, subjects were fed with the next sample of fruit juice until all nine juices (pear, apple, orange, grape, peach, plum, kiwi, melon, and watermelon) had been evaluated. All juices were prepared from pure fruits ground in a home-style mixer. Dietary food records and anthropometric measurements were used to evaluate the nutritional status of subjects. The antioxidant activities of fruit juices were estimated by measuring antioxidant status in the plasma using dichlorofluorescein (DCF) fluorescence. Except for pear juice, eight kinds of juices exhibited potent antioxidant effects in human plasma. Within 30 minutes after consumption, orange, melon, grape, peach, plum, apple, and kiwi juices already effectively suppressed reactive oxygen species generation. This radical scavenging effect of fruit juices was maintained for up to 90 minutes post-consumption, but the relative DCF fluorescence had rebounded to near the initial levels at 2 hours post-consumption in most samples tested. Interestingly, however, grape juice continuously exerted persistent antioxidant activity until 2 hours after supplementation. These results suggest that the consumption of fruits or fruit juices may reduce damage from oxidative stress, and that this effect may be a consequence of the antioxidant activity of fruits in scavenging the reactive oxygen species generated in human plasma. However, long-term studies with more subjects are needed to provide additional supportive evidence and better characterize the antioxidant properties of natural fruit juices.

Measurement of oxidative damage at individual gene levels by quantitative PCR using 8-hydroxyguanine glycosylase (OGG1).

In this study, an attempt was made to develop a method to estimate oxidative damage of individual genes for assessing chemopreventive potential of dietary or medicinal plants. Oxidative damage was investigated on the two genes in gastric mucosal tissue infected with Helicobacter pylori, which were genes of glyceraldehydes-3-phosphate dehydrogenase (GAPDH), a house-keeping gene, and gene of insulin-like growth factor II receptor (IGFIIR), a gene known to be mutated frequently in gastric carcinoma. The oxidative damage in genomic DNA in the above tissue was confirmed by immunohistochemical study using monoclonal antibody to 8-hydroxyguanine (oh(8)G), which showed much higher degree of staining in their nuclei. Using the method we developed, it was demonstrated that the number of oh(8)G (indicated by 8-hydroxyguanine glycosylase (OGG1) sensitive sites) in GAPDH was almost not changed in H. pylori-infected tissue but in IGFIIR, it increased significantly. These results indicate that this method is valid for the estimate of oxidative damage of individual genes and also showed that the susceptibility of genomic DNA to attack of reactive oxygen species is not homogeneous but different depending upon the region of DNA. We expect to use this method in studies of carcinogenic mechanism and chemoprevention since it can provide more specific information pertaining to individual genes we are interested in.

Angiogenic activity of beta-sitosterol in the ischaemia/reperfusion-damaged brain of Mongolian gerbil.

Aloe vera continues to be used for wound healing as a folk medicine. We previously reported that A. vera gel has angiogenic activity. In this study, we report upon the isolation of an angiogenic component beta-sitosterol from A. vera and examination of its effect upon damaged blood vessels of the Mongolian gerbil. In a chick embryo chorioallantoic membrane assay, beta-sitosterol was found to have an angiogenic effect. It enhanced new vessel formation in gerbil brains damaged by ischaemia/reperfusion, especially in the cingulated cortex and septal regions, in a dose-dependent fashion (up to 500 microg/kg, p < 0.05, n = 34 - 40). beta-Sitosterol also enhanced the expressions of proteins related to angiogenesis, namely von Willebrand factors, vascular endothelial growth factor (VEGF), VEGF receptor Flk-1, and blood vessel matrix laminin (p < 0.05, n = 6). In addition, the intraperitoneal administration of beta-sitosterol at 500 microg/kg/day for a period of 19 days significantly improved the motion recovery of ischaemia/reperfusion-damaged gerbils as assessed by rota-rod testing (p < 0.001, n = 10). Our results suggest that beta-sitosterol has therapeutic angiogenic effects on damaged blood vessels.