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Jaeumgeonbi-Tang (JGT), a traditional herbal medicine, has been used to treat dizziness and vertigo in Korea and China for hundreds of years. The purpose of this study was to evaluate the pharmacological properties of JGT in chronic subjective dizziness (CSD) patients. A randomized, double-blind, parallel-group and placebo-controlled trial was performed with a total of 50 CSD patients. The patients were randomly assigned to one of two groups: JGT or placebo (n = 25 for each). All participants received the treatment (placebo or JGT, 24 g/day) for 4 weeks. We analyzed the serum levels of oxidative stressors, antioxidants, and stress hormones. Serum levels of lipid peroxidation, but not nitric oxide, were significantly decreased in the JGT group. JGT not only prevented the decline of serum total glutathione contents and total antioxidant capacity, but it also increased superoxide dismutase and catalase activities. Serum levels of stress hormones including cortisol, adrenaline, and serotonin were notably normalized by JGT treatment, but noradrenaline levels were not affected. Regarding the safety and tolerability of JGT, we found no allergic, adverse, or side effects in any of the participants. JGT showed beneficial effects on CSD patients by improving redox status and balancing psycho-emotional stress hormones. [ABSTRACT FROM AUTHOR]

• SIRT6 deficiency predisposes mice to the development of alcohol-related liver disease. • SIRT6 overexpression ameliorates alcohol-related liver disease. • SIRT6 induces metallothionein genes to protect against oxidative stress. • SIRT6 coactivates metal regulatory transcription factor 1. As a nicotinamide adenine dinucleotide-dependent deacetylase and a key epigenetic regulator, sirtuin 6 (SIRT6) has been implicated in the regulation of metabolism, DNA repair, and inflammation. However, the role of SIRT6 in alcohol-related liver disease (ALD) remains unclear. The aim of this study was to investigate the function and mechanism of SIRT6 in ALD pathogenesis. We developed and characterized Sirt6 knockout (KO) and transgenic mouse models that were treated with either control or ethanol diet. Hepatic steatosis, inflammation, and oxidative stress were analyzed using biochemical and histological methods. Gene regulation was analyzed by luciferase reporter and chromatin immunoprecipitation assays. The Sirt6 KO mice developed severe liver injury characterized by a remarkable increase of oxidative stress and inflammation, whereas the Sirt6 transgenic mice were protected from ALD via normalization of hepatic lipids, inflammatory response, and oxidative stress. Our molecular analysis has identified a number of novel Sirt6-regulated genes that are involved in antioxidative stress, including metallothionein 1 and 2 (Mt1 and Mt2). Mt1/2 genes were downregulated in the livers of Sirt6 KO mice and patients with alcoholic hepatitis. Overexpression of Mt1 in the liver of Sirt6 KO mice improved ALD by reducing hepatic oxidative stress and inflammation. We also identified a critical link between SIRT6 and metal regulatory transcription factor 1 (Mtf1) via a physical interaction and functional coactivation. Mt1/2 promoter reporter assays showed a strong synergistic effect of SIRT6 on the transcriptional activity of Mtf1. Our data suggest that SIRT6 plays a critical protective role against ALD and it may serve as a potential therapeutic target for ALD. The liver, the primary organ for ethanol metabolism, can be damaged by the byproducts of ethanol metabolism, including reactive oxygen species. In this study, we have identified a key epigenetic regulator SIRT6 that plays a critical role in protecting the liver from oxidative stress-induced liver injury. Thus, our data suggest that SIRT6 may be a potential therapeutic target for alcohol-related liver disease. [ABSTRACT FROM AUTHOR]

Objectives. This study investigated whether Sasang constitutional type is associated with differences in the serum levels of stress hormones and oxidative stress. Methods. A total of 236 participants (77 males and 159 females) were enrolled. The serum levels of cortisol, adrenaline, reactive oxygen species (ROS), and malondialdehyde (MDA) were analyzed. Results. The distribution of Sasang constitutional types was as follows: Taeumin, 35.6%; Soumin, 33.0%; and Soyangin, 31.4%. The serum cortisol levels of Taeumin were significantly lower than Soumin (p<0.1 in both sexes) and Soyangin (p<0.05 in males and p<0.1 in females). The adrenaline levels were also significantly lower in Taeumin than in Soumin (p<0.05 in males and p<0.1 in females) and Soyangin (p<0.1 in males). Serum ROS levels were significantly higher in Soyangin than in Taeumin and Soumin (p<0.05 in males), whereas MDA levels were significantly lower in Taeumin compared with Soumin and Soyangin (p<0.05 in males and p<0.1 in females). Conclusion. Taeumin type may tolerate psychological or oxidative stress better than other types, which suggests a biological mechanism to explain the different pathophysiological features of Sasang constitutional types. [ABSTRACT FROM AUTHOR]

This study was performed to evaluate the anti-fatigue effects of Myelophil. ICR male mice (10 weeks old) were forced to run for 1 hour, 5 days/week for 4 weeks. Each running session was followed by administration of distilled water, Myelophil (50 or 100 mg/kg), or ascorbic acid (100 mg/kg) 1 h later. Equal proportions of Astragali Radix and Salviae Miltiorrhizae Radix were extracted using 30% ethanol, and formulated into Myelophil. To evaluate the anti-fatigue effects of Myelophil, exercise tolerance and forced swimming tests were conducted. Underlying mechanisms, including oxidant–antioxidant balance, inflammatory response, and energy metabolism, were investigated by analyzing skeletal muscle tissues and/or sera. Myelophil significantly increased exercise ability and latency times, and decreased the number of electric shocks and immobility time on exercise tolerance and forced swimming tests compared with control group. Myelophil also significantly ameliorated fatigue-induced alterations in oxidative stress biomarkers, antioxidant enzymes and antioxidant capacity, as measured by multiple assays, including enzyme activity assays and western blotting, as well as alterations in pro- and anti-inflammatory cytokines in skeletal muscle. Furthermore, Myelophil normalized alterations in energy metabolic markers in sera. These findings suggest that Myelophil reduces the effects of chronic fatigue, likely by attenuating oxidative and inflammatory responses and normalizing energy metabolism. Consequently, this study provides evidence for the clinical relevance of Myelophil. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Myelophil, a combination of extracts taken from Astragali Radix and Salviae Miltiorrhizae Radix, is a traditional Chinese medicine used for the treatment of chronic fatigue-associated disorders. Here we examined the ability of Myelophil to alleviate memory impairment in a mouse model. We aimed to investigate whether Myelophil has the pharmacological effects on memory deficits associated with brain dysfunctions using an animal model. Materials and methods: Ten week-old male C57BL/6N mice were pretreated with Myelophil (50, 100, or 200mg/kg), or tacrine (10mg/kg) for 7 days, and then intraperitoneally injected with scopolamine (1mg/kg). Memory-related behaviors were evaluated using the Morris water maze for 5 days. Levels of biomarkers of oxidative stress, antioxidant activity, acetylcholinesterase (AChE) activity, and extracellular signal-regulated kinase (ERK) were measured in brain tissues. Results: Scopolamine treatment increased the escape latency time and shortened time spent in the target quadrant; these effects were ameliorated by pretreatment with Myelophil. Scopolamine-induced changes in reactive oxygen species (ROS), malondialehyde (MDA), and AChE activity were significantly attenuated in mice pretreated with Myelophil. Recovery of antioxidant capacities, including total glutathione (GSH) content, and the activities of GSH-reductase, GSH-S-transferase, and catalase was also evident in Myelophil-treated mice. The strongest effects were seen for ERK and muscarinic acetylcholine receptor 1 (mAChR1) at both the protein and gene expression levels, with significant amelioration of expression levels in the Myelophil pretreatment group. Conclusions: These results suggest that Myelophil confers anti-amnesic properties in a mouse model of memory impairment, driven in part by the modulation of cholinergic activity. [Copyright &y& Elsevier]

Myelophil, an ethanolic extract of Astragali Radix and Salviae Radix, has been clinically used to treat chronic fatigue and stress related disorders in South Korea. In this study, we investigated the protective effects of Myelophil on a whisker removal-induced psycho-emotional stress model. SD rats were subjected to whisker removal after oral administration of Myelophil or ascorbic acid for consecutive 4 days. Whisker removal considerably increased total reactive oxygen species in serum levels as well as cerebral cortex and hippocampal regions in brain tissues. Lipidperoxidation levels were also increased in the cerebral cortex, hippocampus regions, and brain tissue injuries as shown in histopathology and immunohistochemistry. However, Myelophil significantly ameliorated these alterations, and depletion of glutathione contents in both cerebral cortex and hippocampus regions respectively. Serum levels of corticosterone and adrenaline were notably altered after whisker removal stress, whereas these abnormalities were significantly normalized by pre-treatment with Myelophil. The NF-κB was notably activated in both cerebral cortex and hippocampus after whisker removal stress, while it was efficiently blocked by pre-treatment with Myelophil. Myelophil also significantly normalizes alterations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and interferon-γ in both gene expressions and protein levels. These results suggest that Myelophil has protective effects on brain damages in psycho-emotional stress, and the underlying mechanisms involve regulation of inflammatory proteins, especially NF-κB modulation. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacologic relevance: The Chunggan extract (CGX) is a traditional herbal formula prescribed for patients suffering from various liver diseases, including alcoholic liver disease, in which the mechanism of CGX action remains unclear. This study aimed to investigate the anti-hepatic fibrosis effects of CGX and its underlying mechanisms in alcohol-induced rat livers. Materials and methods: To elucidate the mechanism of action of CGX, we evaluated gene expression profiles in the livers of rats treated with 30% alcohol and anti-fibrotic doses of CGX of 100 and 200mg/kg/day at 1 day, and 2 and 4 weeks using microarrays. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF), one of the candidate genes selected in this study, in alcohol-induced rat livers were measured by real-time PCR and enzyme-linked immunosorbent assays, respectively. Results: We identified 4128 genes as differentially expressed by at least twofold between alcohol-only– and alcohol–CGX–fed rats at various doses and time points, compared to naïve control animals. Twenty-three of these genes were associated with liver fibrosis and oxidative stress based on the GeneCards database, resulting in p<0.05 by ANOVA between the alcohol-only and alcohol–CGX groups. Especially, Vegf was decreased in CGX 200mg/kg/day-fed rat livers at all time points evaluated, and mRNA and protein levels at the 4-week time point were validated. Conclusion: These gene expression profiles provide a better understanding of the mechanisms underlying the anti-fibrotic effects of CGX. Suppression of VEGF may play a critical role in anti-fibrotic action of CGX in alcoholic liver injury. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Myelophil is composed of Astragali Radix and Salviae Miltiorrhizae Radix, according to the long traditional pharmacological practices, and it has been used for patients with chronic fatigue-associated symptoms including concentration problem or memory loss. Aim of the study: This study aimed to evaluate the clinical relevance of Myelophil on brain oxidative damage using a chronic cold stress mice model. Material and methods: Balb/c mice were subjected to cold stress (4°C for 4h) six times per week for 2 weeks with or without oral administration of Myelophil (50, 100, or 200mg/kg), or ascorbic acid (50mg/kg). Results: Chronic cold stress induced histopathological hippocampal apoptosis with drastically increased serum levels of total reactive oxygen species and nitric oxide, as well as brain lipid peroxidation levels, protein carbonyl, and caspase-3/7 activity. These alterations were significantly ameliorated by Myelophil treatment. Myelophil administration significantly recovered the depleted glutathione and its enzymes, superoxide dismutase activity, and catalase protein and gene expression levels. Serum levels of corticosterone, dopamine, and adrenaline were notably altered by chronic cold stress but were significantly ameliorated by Myelophil treatment. Myelophil also normalized alterations in tumor necrosis factor-α, interleukin (IL)-1β, and IL-10 gene expression and protein levels. Chronic cold stress up-regulated gene expression levels of phenylethanolamine N-methyltransferase and monoamine oxidase-B, and glucocorticoid receptors in the hypothalamus and hippocampus, respectively, whereas Myelophil treatment completely normalized these levels. Conclusions: These results suggest that Myelophil has potent pharmaceutical effects against chronic cold-stress-induced brain damage by relieving oxidative stress and inflammation and regulating stress hormones in mice. [Copyright &y& Elsevier]

Purpose: The modification of radiation-induced lung injuries by melatonin was studied by measuring changes in oxidative stress, cytokine expression and histopathology in the lung tissue of mice following irradiation. Materials and methods: The thoraces of C57BL/6 mice were exposed to a single X-ray radiation dose of 12 Gy with or without 200 mg/kg of melatonin pretreatment. The level and localization of transforming growth factor (TGF)-β1 protein were measured using an enzyme-linked immunosorbent assay (ELISA) method and immunohistochemical staining, respectively. Real-time quantitative polymerase chain reaction (PCR) was established to evaluate the relative mRNA expression levels of TGF-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. Results: Malondialdehyde (MDA) levels increased after irradiation and then significantly reduced (1.9-fold) under melatonin treatment. Changes in superoxide dismutase (SOD) and catalase activities, as well as glutathione (GSH) levels, after irradiation were significantly reduced by melatonin, including a notable 5.4-fold difference in catalase activity. We observed increased expression of TGF-β1 and TNF-α after irradiation and a significant reduction in the elevation of their expression by melatonin treatment. Furthermore, irradiation-induced histopathologic alterations were obviously abated in the melatonin-pretreated mice. Conclusions: The present results suggest that melatonin reduces radiation-induced lung injury via a significant reduction of oxidative stress and of the production of cytokines, such as TGF-β1 and TNF-α, the production of which increased following lung irradiation. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacologic relevance: CGX is a modification of a traditional herbal medicine that has been used for various liver disorders as a meaning of “cleaning the liver”. The cholestatic liver disorders become prevalent. Back ground and aim: This study aimed to investigate the anti-hepatic fibrosis effects of CGX and its underlying mechanisms in a rat model of bile duct ligation (BDL). Materials and methods: BDL was conducted in SD rats except shame operation group. The rats were orally administrated with distilled water, CGX (25 or 50mg/kg) or ursodeoxycholic acid (UDCA, 25mg/kg) for two weeks. The pharmaceutical effects and mechanisms were analyzed in histopathology, biochemistry, oxidative stress/antioxidant biomarkers and hepatic fibrogenic cytokines levels. Results: BDL markedly elevated white blood cell (WBC) counts as well as changed subset proportions such as increased neutrophils and decreased lymphocytes in peripheral blood. BDL drastically elevated the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, and hepatic tissue levels of hydroxyproline and malondialdehyde (MDA), while it reduced the total glutathione (GSH) content and the activities of GSH-redox system enzymes such as GSH-peroxidase, GSH-reductase and GSH-S-transferase. These alterations were significantly attenuated by CGX treatment (mainly 50mg/kg). CGX treatment normalized both the accumulation of collagen in hepatic tissue and the increased levels of profibrogenic cytokine including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). Moreover, CGX treatment enhanced interferon-gamma (IFN-γ) expression compare to the BDL group at the protein and gene level. Conclusion: These results suggest that CGX exerts anti-hepatofibrotic effect in rat BDL model, and the responsible mechanisms involve the inhibition of hepatic fibrogenic cytokines and oxidative stress. [Copyright &y& Elsevier]

Abstract: Cholestatic liver fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins, is associated with bile acid-induced oxidative stress and lipid peroxidation. We evaluated the therapeutic or protective effect of an aqueous extract of Artemisia iwayomogi Kitamura (WAI) in a rat bile duct ligation (BDL)-induced hepatic fibrogenesis model. After BDL, rats were treated once daily with 25 or 50mg/kg of WAI for 2weeks. The serum bilirubin, aspartate transaminase, alanine transaminase, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group. WAI administration significantly reduced these markers and restored BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAI treatment, and these changes were paralleled by significantly suppressed gene and protein expression of fibrogenic factors, including hepatic alphasmooth muscle actin, platelet-derived growth factor, and transforming growth factor β. Our data suggest that WAI may have antifibrotic properties via both improvement of antioxidant activities and inhibition of ECM protein production in the rat model of BDL. [Copyright &y& Elsevier]

Abstract: We investigated the antioxidant effects of Panax ginseng C.A. Meyer on healthy volunteers. In a double-blind randomized controlled design, 82 participants (21 men and 61 women) who were considered healthy by both objective and subjective health standard were divided into three groups, the control group and the groups received P. ginseng extract (1 or 2g/day) for 4weeks. Serum level of reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC), the activities of catalase, superoxide dismutase (SOD), glutathione reductase (GSH-Rd), and peroxidase (GSH-Px), and total glutathione content were determined before and after the trial. Administration of P. ginseng led to significant decreases in the levels of serum ROS and MDA. Notably, the total glutathione content and GSH-Rd activity considerably improved in the groups that received 2g of P. ginseng. No significant alterations were observed in TAC, catalase, SOD, and GSH-Px activities. In conclusion, our findings indicate that P. ginseng was shown to have antioxidant property. It enhanced the antioxidant defense mechanism in healthy populations and the results may reinforce the use of P. ginseng as a potential antioxidant supplement. [Copyright &y& Elsevier]

The dysbiosis of gut microbiota may cause many complications in patients with end-stage renal disease, which may be alleviated by probiotic, prebiotic, and synbiotic supplementation. The aim of this systematic review and meta-analysis was to assess the effects of these supplementations on circulatory uremic toxins, biomarkers of inflammation, and oxidative stress in hemodialysis patients. We searched the EMBASE, MEDLINE, Web of Science, and Cochrane Library databases until 8 August 2021. Randomized controlled trials evaluating adult patients receiving hemodialysis were included. The pooled results from 23 studies with 931 hemodialysis patients indicated that interventions significantly decreased the circulating levels of p-cresyl sulfate (standardized mean difference (SMD): 0.38; 95% CI: −0.61, −0.15; p = 0.001), endotoxins (SMD: −0.58; 95% CI: −0.99, −0.18; p = 0.005), malondialdehyde (SMD: −1.16; 95% CI: −1.81, −0.52; p = 0.0004), C-reactive proteins (CRP) (SMD: −0.61; 95% CI: −0.99, −0.23; p = 0.002), and interleukin 6 (SMD: −0.92; 95% CI: −1.51, −0.33; p = 0.002), and improved the total antioxidant capacity (SMD: 0.89; 95% CI: 0.49, 1.30; p < 0.0001) and glutathione (SMD: 0.40; 95% CI: 0.14, 0.66; p = 0.003) when compared to the placebo group. Our results suggest that treatment with probiotics, prebiotics, and synbiotics may help alleviate uremic toxin levels, oxidative stress, and the inflammatory status in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Traditional Chinese/Korean medicine suggests " blood stasis (瘀血)", " stagnation of vital energy (气滯)" and " dampness and Phlegm (湿痰)" as the main etiologies of liver disorders, and multiherbal formulas are generally believed to exert synergistic action. The present study aimed to investigate the synergistic hepatoprotective effects of CGplus (a mixture of Salviae miltiorrhiza , Artemisia iwayomogi and Ammomum xanthioides) compared to those of the individual herbs. A total of fifty-six male Balb/C mice were randomly divided into eight groups and were administered water (normal and CCl 4 groups), 100 mg/kg S. miltiorrhiza , A. iwayomogi , or A. xanthioides , 50 or 100 mg/kg CGPlus or dimethyl dimethoxybiphenyl dicarboxylate (DDB) as a positive control for 4 consecutive days. After a single CCl 4 injection (i.p., 10 mL/kg of 0.2% CCl 4 in olive oil), blood and liver tissues were collected after 18 h of fasting for serum biochemistry, histopathological examination and molecular analyses. CCl 4 injection induced drastic hepatic injury characterized by a more than 30-fold increase in the release of AST and ALT into the serum. These alterations were significantly attenuated by pretreatment with each of the three herbs, while the effects of the individual herbs were synergistically augmented by CGPlus pretreatment. The synergistic hepatoprotective actions of CGPlus were demonstrated consistently by analyses of oxidative stress (oxidative stressors, oxidation products and antioxidant enzymes), pro-/anti-inflammatory cytokines (TNF-ɑ, IL-1β, IL-6, IL-10), and apoptosis (caspase-3, p53 and BAX) and histopathology. These data suggest that CGPlus exerts its hepatoprotective effects in a synergistic manner, and further studies are required for clinical application using other chronic models. Image 1 [ABSTRACT FROM AUTHOR]

Oxidative stress is a common phenomenon and is linked to a wide range of diseases and pathological processes including aging. Tissue-specific variation in redox signaling and cellular responses to oxidative stress may be associated with vulnerability especially to age-related and chronic diseases. In order to provide a basis for tissue-specific difference, we examined the tissue-specific transcriptional features of 101 oxidative stress-associated genes in 10 different tissues and organs of healthy mice under physiological conditions. Microarray analysis results, which were consistent with quantitative polymerase chain reaction (qPCR) results, showed that catalase, Gpx3, and Gpx4 were most highly regulated in the liver, kidney, and testes. We also found the tissue-specific gene expression of SOD1 (liver and kidney), SOD2 (heart and muscle), and SOD3 (lung and kidney). The current results will serve as a reference for animal models and help advance our understanding of tissue-specific variability in oxidative stress-associated pathogenesis. [ABSTRACT FROM AUTHOR]

Chlorogenic acid (CGA) is a major component of green coffee beans. Surfactin, a cyclic lipopeptide, is produced and secreted by Bacillus subtilis strains. In this study, bioactivities of fermented green coffee bean extract (FGCBE) and the individual compounds, CGA and surfactin. were compared in HepG2 cells. The concentration of surfactin and CGA in the FGCBE and non-fermented green coffee bean extract (NFGCBE) were determined to be 9.2 and 7.33 and 0.72 and 0.53 mg·mL−1, respectively. The FGCBE contained about 20% and 26% more CGA and surfactin than the NFGCBE. Although CGA and surfactin exhibited cytotoxicity at concentrations more than 100 and 20 μg respectively, the FGCBE 50 containing CGA (460 μg·mL−1) and surfactin (720 μg·mL−1) effectively prevented cell death by oxidative stress and also strongly activated the proliferation of cells incubated with under 50 μM H2O2. The CGA and surfactin in FGCBE were 9.2 and 72 times higher than the CGA and surfactin compounds (50 and 10 μg·mL−1). The relative proliferation of the FGCBE-treated cells also was 3.3 and 8.8 times higher than the CGA and surfactin compounds treated the oxidative stressed cells with 50 μM H2O2. These results suggest that the single compounds such as CGA and surfactin generally have cytotoxicity at low concentration of them but FGCBE contained them acted as strong antioxidants, activators of cell proliferation, inhibitors of cell apoptosis. Various bioactive compounds in fermented coffee bean also seem to help cell proliferation and decreasing of cytotoxicity by CGA and surfactin in coffee bean. [ABSTRACT FROM AUTHOR]

It is well known that oxidative stress is highly associated with Parkinson's disease (PD), and biliverdin reductase A (BLVRA) is known to have antioxidant properties against oxidative stress. In this study, we developed a novel N‐acetylgalactosamine kinase (GK2) protein transduction domain (PTD) derived from adenosine A2A and fused with BLVRA to determine whether the GK2‐BLVRA fusion protein could protect dopaminergic neuronal cells (SH‐SY5Y) from oxidative stress in vitro and in vivo using a PD animal model. GK2‐BLVRA was transduced into various cells, including SH‐SY5Y cells, without cytotoxic effects, and this fusion protein protected SH‐SY5Y cells and reduced reactive oxygen species production and DNA damage after 1‐methyl‐4‐phenylpyridinium (MPP+) exposure. GK2‐BLVRA suppressed mitogen‐activated protein kinase (MAPK) activation and modulated apoptosis‐related protein (Bcl‐2, Bax, cleaved Caspase‐3 and ‐9) expression levels. In the PD animal model, GK2‐BLVRA transduced into the substantia nigra crossed the blood–brain barrier and markedly reduced dopaminergic neuronal cell death in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced animals. These results indicate that our novel PTD GK‐2 is useful for the transduction of protein, and GK2‐BLVRA exhibits a beneficial effect against dopaminergic neuronal cell death in vitro and in vivo, suggesting that BLVRA can be used as a therapeutic agent for PD. [ABSTRACT FROM AUTHOR]

Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The medicinal plants Artemisia iwayomogi and Curcuma longa radix are both used to treat hyperlipidemia in traditional Korean and Chinese medicine. Aim of the study To evaluate the anti-hyperlipidemic effects of the 30% ethanol extracts of A. iwayomogi (AI), C. longa (CL), and the mixture of A. iwayomogi and C. longa (ACE), using a high-fat diet-induced hyperlipidemia model. Materials and methods Six of seven groups of C57BL/6N male mice (i.e., not including the naïve group) were fed a high-fat diet freely for 10 weeks. Of these six groups, five (i.e., not including the control group) were administered a high-fat diet supplemented with AI (100 mg/kg), CL (100 mg/kg), ACE (50 or 100 mg/kg), or Lipitor (20 mg/kg). Serum lipid profiles, obesity-related markers, hepatic steatosis, hepatic gene expression, and oxidative stress markers were analyzed. Results AI, CL, and ACE were associated with significant effects on serum lipid profiles (total cholesterol [TC] and triglyceride), body, liver and peritoneal adipose tissue weights, hepatic lipid accumulation, and oxidative stress biomarkers. ACE at 100 mg/kg was associated with significantly greater improvements in serum TC and triglyceride, hepatic triglyceride, epididymal adipocyte size, and oxidative stress biomarkers, compared with AI and CL. AI, CL and ACE normalized lipid synthesis-associated gene expression (peroxisome proliferator-activated receptor gamma, fatty acid synthase, sterol regulatory element-binding transcription factor-1c, and peroxisome proliferator-activated receptor alpha). Conclusion ACE exhibits anti-hyperlipidemia properties and is associated with partially synergistic effects compared with AI or CL alone. [ABSTRACT FROM AUTHOR]

Background Kouksundo is a traditional Korean mind–body practice that has been practiced for thousands of years. We investigated the effects of Kouksundo on oxidative stress-related biomarkers and stress hormones. Methods A single-arm observational study was conducted on 57 Kouksundo trainees (34 males and 23 females). Blood samples were collected 30 min before and after Kouksundo practice (25 min for warm-up, 45 min for breathing meditation, and 20 min for cool-down). Results Kouksundo significantly reduced serum levels of oxidant markers, including reactive oxygen species ( p < 0.01), nitric oxide ( p < 0.01), and malondialdehyde ( p < 0.05), induced elevation of superoxide dismutase ( p < 0.01), and reduction of catalase ( p < 0.001). No significant changes were observed in total antioxidant capacity or total glutathione content levels ( p > 0.05). Kouksundo practice also significantly reduced the serum level of cortisol ( p < 0.001), norepinephrine ( p < 0.001), and dopamine ( p < 0.05), and significantly increased serum epinephrine concentrations ( p < 0.05). Conclusion The traditional Korean mind–body practice Kouksundo provided health benefits by regulating oxidative stress and levels of stress hormones. This study is the first investigation of the changes in oxidative stress and stress hormones induced by mind–body therapy, producing reference data for mechanistic studies on these practices. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacologic relevance: Artemisia capillaris, also called “InJin” in Korean, has been widely used to treat various hepatic disorders in traditional Oriental medicine. Aims: The purpose of this study is to evaluate the hepatoprotective effect of Artemisia capillaris (aqueous extract, WAC) on alcoholic liver injury. Materials and methods: Liver injury was induced by oral administration of 30% alcohol (10mL/kg, twice per day) plus pyrazole (PRZ, 30mg/kg) with/without WAC (50, 100mg/kg, orally once per day) or silymarin (50mg/kg) for 10 days. The hepatoprotective effects were assessed by observing histopathological changes, hepatic transaminase enzymes, hepatic oxidation and antioxidant parameters, inflammatory cytokines, and alcohol metabolic enzymes in serum and hepatic gene expression level, respectively. Results: Alcohol–PRZ treatment drastically increased the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels in serum and liver tissues while these changes were significantly ameliorated by WAC administration (p<0.05 or 0.01). The prominent microvesicular steatosis and mild necrosis in hepatic histopathology were induced by alcohol–PRZ treatment, but notably attenuated by WAC administration. Moreover, the alcohol–PRZ treatment-induced depletions of the antioxidant components including glutathione content, total antioxidant capacity (TAC), activities of glutathione peroxidase (GSH-Px), reductase (GSH-Rd), catalase, and superoxide dismutase (SOD) were significantly ameliorated by WAC administration (p<0.05, except GSH-Rd). These results were in accordance with the modulation of NF-E2-related factor (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Alcohol–PRZ treatment increased the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in hepatic tissues. However they were significantly normalized by WAC administration (p<0.05 or 0.01). In addition, WAC administration significantly attenuated the alterations of aldehyde dehydrogenase (ALDH) level in serum and hepatic gene expressions of ALDH and alcohol dehydrogenase (ADH). Conclusions: These results support the relevance in clinical use of Artemisia capillaris for alcohol-associated hepatic disorders. The underlying mechanisms may involve both enhancement of antioxidant activities and modulation of proinflammatory cytokines. [Copyright &y& Elsevier]

Abstract: Objective: Atherosclerosis in patients with type 2 diabetes has been linked to oxidative stress. NADP[1]:quinone oxidoreductase 1 (NQO1) plays a key role in cellular antioxidant defense. Recent reports suggest that highly expressed and inducible endogenous NQO1 from cardiovascular cells may act as a potential superoxide scavenger. We examined the relationship between the risk of NQO1 C609T polymorphism and carotid artery atherosclerosis in patients with type 2 diabetes. Methods: We recruited 601 (Seoul set) and 233 (Koyang set) unrelated patients with type 2 diabetes from independent groups. The C609T variant of NQO1 was genotyped by Taqman RT-PCR. Mean and maximum carotid intima-media thickness (IMT) and carotid artery plaques were measured by high-resolution ultrasonography. Results: Patients with the T allele exhibited a higher prevalence of atherosclerotic plaques than non-T allele carriers in both sets (Seoul set vs. Koyang set, p =0.021, p =0.023, respectively). After adjusting for age, sex, duration of diabetes, systolic blood pressure, body mass index, current smoking, HDL-cholesterol, LDL-cholesterol and HbA1c, subjects with the T allele had a significantly higher risk of carotid artery plaques (Seoul set vs. Koyang set, OR=1.65, p =0.015; OR=2.00, p =0.037, respectively) than subjects with the CC genotype. Conclusion: These results suggest that the C609T polymorphism of NQO1 is associated with carotid artery plaques in type 2 diabetic patients. [Copyright &y& Elsevier]

We evaluated neuropharmacological properties of Yuk-Mi-Jihwang-Tang (YJT) against scopolamine injection-induced memory impairment mice model. Mice were orally administered with YJT (50, 100, or 200 mg/kg) or tacrine (TAC, 12.5 mg/kg) for 10 days. At the first day of Morris water maze task, scopolamine (2 mg/kg) was intraperitoneally injected before 30 min of it. The hippocampal memory function was determined by the Morris water maze task for 5 days consecutively. Scopolamine drastically increased escape latency and decreased time spent in target quadrant. Pretreatment YJT properly improved them. Regarding the redox status, YJT significantly reduced the oxidative stress and it also exerted much effort to improve both superoxide dismutase and catalase activities in hippocampal gene expression and protein levels. These effects were well coincided with immunohistochemical analysis of 4-hydroxyneal-positive signals in hippocampal areas. Additionally, acetylcholine esterase activities and brain-derived neurotrophic factor abnormalities in the hippocampal protein levels were significantly normalized by YJT, and their related molecules were also improved. The neuronal proliferation in hippocampal regions was markedly inhibited by scopolamine, whereas YJT notably recovered them. Collectively, YJT exerts much effort to enhance memorial functions through improving redox status homeostasis and partially regulates acetylcholine esterase activities as well as neuronal cell proliferation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Gongjin-Dan is a representative traditional Oriental medicine herbal drug that has been used to treat chronic fatigue symptoms for several hundred years. We evaluated the anti-fatigue effects of Gongjin-Dan and the underlying mechanisms in a chronic forced exercise mouse model. Methods and materials Balb/C male mice underwent an extreme treadmill-based running stress (1-h, 5 days/week), and daily oral administration of distilled water, Gongjin-Dan (100, 200, or 400 mg/kg), or ascorbic acid (100 mg/kg) for 28 days. The anti-fatigue effects of Gongjin-Dan were evaluated with behavioral tests (exercise tolerance and swimming tests), and the corresponding mechanisms were investigated based on oxidative stress and inflammatory cytokine and stress hormone levels in skeletal muscle, sera, and brain tissue. Results Gongjin-Dan significantly increased exercise tolerance and latency times but reduced the number of electric shocks and immobilization time on the treadmill running and swimming tests, compared with the control group. Gongjin-Dan also significantly ameliorated alterations in oxidative stress-related biomarkers (reactive oxygen species and malondialdehyde), inflammatory cytokines (tumor necrosis factor-α, interleukin-1 beta, interleukin-6, and interferon-γ) and glycogen and l -lactate levels in skeletal muscle, compared with those in the control group. Moreover, Gongjin-Dan considerably normalized the forced running stress-induced changes in serum corticosterone and adrenaline levels, as well as brain serotonin level. These antioxidant and anti-stress effects of Gongjin-Dan were supported by the results of Western blotting (4-hydroxynonenal and heme oxygenase-1) and the gene expression levels (serotonin receptor and serotonin transporter). Conclusion These results support the clinical relevance of Gongjin-Dan regarding anti-chronic fatigue properties. The underlying mechanisms involve attenuation of oxidative and inflammatory reactions in muscle and regulation of the stress response through the hypothalmo-pituitary-adrenal axis. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Uwhangchungsimwon (UCW) is a representative traditional herbal medicine for central nervous system disorders in East Asia countries over thousand years. To evaluate the pharmacological effects of UCW against oxidative brain injury in a chronic restraint stress mice model. Methods and materials: C57BL/6 male mice underwent daily oral administration of distilled water, UCW or ascorbic acid 1h before induction of restraint stress (5h of immobilization daily for 14 days). Nitric oxide (NO), total reactive oxygen species (ROS) levels, malondialdehyde, protein carbonyl contents, and activities of antioxidant enzymes, and concentrations of corticosterone, adrenaline, noradrenaline, and dopamine, were measured in brain tissues or sera. Results: Restraint stress notably increased NO and ROS levels, malondialdehyde and protein carbonyl contents in brain tissues, but decreased activities of catalase, glutathione reductase and glutathione peroxidase. These alterations were significantly ameliorated by UCW. UCW significantly attenuated the elevated serum concentrations of corticosterone, adrenaline and noradrenaline. UCW also significantly normalized the gene expressions in brain tissues altered by restraint stress; up-regulation of phenylethanolamine N-methyltransferase (PNMT) and N-methyl-d-aspartate type 1 receptor (NMDAR1), and down-regulation of gamma-Aminobutyric acid type A receptor (GABAAR), glutamate decarboxylase 1 (GAD 67), and glutamate decarboxylase 2 (GAD 65), respectively. Moreover, UCW considerably restored neurogenesis in the hippocampal regions which was disturbed by chronic restraint stress. Conclusions: These results evidenced that UCW has pharmacological properties for brain protection and neurogenesis in status of stress-associated oxidative damage, and the underlying mechanisms involve the regulation of HPA axis in stress responses. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Phragmites rhizoma was reported to have anti-oxidative and free radical scavenging activity. It also has been traditionally used to suppress inflammation. In the present study, we aimed to evaluate the topical effects of the polysaccharide-rich extract of P. rhizoma (PEP) on atopic dermatitis. Main methods: We induced AD-like skin lesions by an extract of the house-dust mite Dermatophagoides farinae (Dfb) in NC/Nga mice, and then performed macroscopic analysis, immunohistochemical staining and measurement of total serum IgE and cytokine production by ELISA. Key findings: Topically applied PEP suppressed dermatitis with a decrease in dermatitis score and scratch number. The histological manifestations of atopic skin lesions including thickened epidermis and increased numbers of mast cells, polymorphonuclear leukocytes and nerve fibers were significantly attenuated. The activation of IgE and the levels of cytokines such as IFN-γ IL-4 and IL-10 were also decreased. Significance: Our results indicated that PEP might have an inhibitory effect on atopic dermatitis-like lesion and be a promising natural resource in the treatment of atopic dermatitis. [Copyright &y& Elsevier]

Abstract: Aim of the study: Amomum xanthoides is a well-known traditional herbal medicine mainly for diverse digestive system disorders in Asia for a long time. In the present study, we investigate the effects and action mechanism of methanol fraction of Amomum xanthoides (MFAX) on thioacetamide (TAA)-induced liver fibrosis in rat model. Materials and methods: TAA (200mg/kg, ip on twice a week for 14 weeks) treated rats were orally administered with MFAX (25, 50 or 100mg/kg) once a day from the 7th week until 14th week. Result: Significantly elevated serum bilirubin, liver tissue hydroxyproline and malondialdehyde (MDA) in liver fibrosis were ameliorated by MFAX treatment. Further, MFAX treatment attenuated the reactive oxygen species (ROS) levels and restored glutathione (GSH) content and glutathione-peroxidase (GPx) activity. Histopathological data showed that MFAX treatment inhibited collagen accumulation and activation of hepatocyte stellate cells (HSCs) in the liver tissue. Compared to the TAA group, activation of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), platelet-derived growth factor beta (PDGF-β) mRNAs and the level of pro-fibrotic cytokines PDGF-β and connective tissue growth factor (CTGF) in the liver tissue were attenuated in MFAX treated groups. Conclusion: The above evidences collectively indicate that MFAX is a potential herb which can be used as an anti-hepatofibrotic remedy. [Copyright &y& Elsevier]