Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model.

Background: Ursodeoxycholic acid (UDCA), statins, and ezetimibe (EZE) have demonstrated beneficial effects against non-alcoholic fatty liver disease (NAFLD). We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin (RSV)/EZE in the treatment of NAFLD. Methods: NAFLD mouse models were developed by injecting thioacetamide, fasting, and high-carbohydrate refeeding, high-fat diet, and choline-deficient L-amino acid-defined high-fat diet (CDAHFD). Low-dose UDCA (L-UDCA; 15 mg/kg) or high-dose UDCA (H-UDCA; 30 mg/kg) was administered with RSV/EZE. We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells. Results: Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation, serum alanine aminotransferase (ALT) levels, and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice (all P < 0.01). In addition, in the group fasted and refed with a high-carbohydrate diet, UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group (all P < 0.05). Subsequently, H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1 (SCD-1) mRNA levels (P = 0.027) in the liver of high-fat diet-fed mice compared with those observed in the vehicle group. In the CDAHFD-fed mouse model, UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group (all P < 0.05). In addition, UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells (all P < 0.05). Conclusion: Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.

E-cigarette-associated Severe Pneumonia in Korea Using Data Linkage between the Korea National Health and Nutrition Examination Survey (KNHANES, 2013-2019) and the National Health Insurance Service (NHIS) Claims Database.

BACKGROUND: This study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database. METHODS: We conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay. RESULTS: The final analysis included 28,950 individuals, of which 578 (2.0%) were EC users. EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000). CONCLUSIONS: Since e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.

Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness.

Vitamin D (VitD) has pleiotropic effects. VitD deficiency is closely involved with obesity and may contribute to the development of lung fibrosis and aggravation of airway hyperresponsiveness (AHR). We evaluated the causal relationship between VitD deficiency and the lung pathologies associated with obesity. In vivo effects of VitD supplementation were analyzed using high-fat diet (HFD)-induced obese mice and TGF-ß1 (transforming growth factor-ß1) triple transgenic mice. Effects of VitD supplementation were also evaluated in both BEAS-2B and primary lung cells from the transgenic mice. Obese mice had decreased 25-OH VitD and VitD receptor expressions with increases of insulin resistance, renin and angiotensin-2 system (RAS) activity, and leptin. In addition, lung pathologies such as a modest increase in macrophages, enhanced TGF-ß1, IL-1ß, and IL-6 expression, lung fibrosis, and AHR were found. VitD supplementation to HFD-induced obese mice recovered these findings. TGF-ß1-overexpressing transgenic mice enhanced macrophages in BAL fluid, lung expression of RAS, epithelial-mesenchymal transition markers, AHR, and lung fibrosis. VitD supplementation also attenuated these findings in addition to the attenuation of the expressions of TGF-ß1, and phosphorylated Smad-2/3 in lung. Supplementing in vitro-stimulated BEAS-2B and primary lung cells with VitD inhibited TGF-ß1 expression, supporting the suppressive effect of VitD for TGF-ß1 expression. These results suggest that obesity leads to VitD deficiency and worsens insulin resistance while enhancing the expression of leptin, RAS, TGF-ß1, and proinflammatory cytokines. These changes may contribute to the development of lung fibrosis and AHR. VitD supplementation rescues these changes and may have therapeutic potential for asthma with obesity.

Colistin monotherapy versus colistin/rifampicin combination therapy in pneumonia caused by colistin-resistant Acinetobacter baumannii: A randomised controlled trial.

OBJECTIVES: The aim of this study was to confirm the synergistic effect of colistin/rifampicin combination therapy compared with colistin monotherapy in pneumonia caused by colistin-resistant Acinetobacter baumannii (CoRAB). The utility of the Etest was also assessed. METHODS: Nine subjects with pneumonia caused by CoRAB were enrolled from 20 July 2016 to 21 June 2018. Subjects were randomised to colistin/rifampicin combination therapy or colistin monotherapy. After exclusion of one patient who dropped out, the microbiological response (MR) and clinical response (CR) on Day 14 and mortality on Day 30 were assessed. Etest was conducted using CoRAB isolated at study enrolment. RESULTS: The MR rate in the colistin/rifampicin combination group (100.0%) was better than that in the colistin group (40.0%), however the difference was not statistically significant (P=0.196). The CR rate was not significantly different between the two groups. The MR (100.0%) and CR (100.0%) rates in subjects with 'partial synergy' as shown by Etest were higher than those (25.0% and 50.0%, respectively) in subjects with 'indifferent' results (i.e. no synergistic effect), however the difference was not statistically significant (P=0.143 and 0.429, respectively). Mortality occurred in two subjects with 'indifferent' results by Etest. CONCLUSIONS: Colistin/rifampicin combination therapy may have potential to achieve MR in pneumonia caused by CoRAB; however, achieving CR with this treatment is doubtful. 'Partial synergy' of colistin and rifampicin, as shown by Etest, may be a good prognostic factor [ClinicalTrial.gov ID: NCT03622918].

Efficacy of adjuvant chemotherapy for completely resected stage IB non-small cell lung cancer: a retrospective study.

BACKGROUND: Lung cancer is being increasingly detected in the early stages, highlighting the importance of lung cancer screening. However, there is no consensus on the post-operative management of stage IB non-small cell lung cancer (NSCLC). Therefore, this study aimed to identify the predictive factors for prognosis of stage IB NSCLC and determine the efficacy of adjuvant chemotherapy on recurrence and survival. METHODS: We enrolled 89 patients with stage IB NSCLC who underwent complete resection surgery at Gangnam Severance Hospital from Jan 2008 to Dec 2014. As per the National Comprehensive Cancer Network guidelines, patients were considered to be at high risk when they showed poorly differentiated tumors, lymphovascular invasion, tumor size >4 cm, and visceral pleural invasion (VPI). RESULTS: Among the 89 patients, 27 underwent adjuvant chemotherapy. Young patients or patients with squamous cell lung cancer received adjuvant chemotherapy frequently. Adjuvant chemotherapy was not a significant factor for disease-free survival and overall survival. Adjuvant chemotherapy did not show a significant protective effect for survival, even for high-risk patients. However, VPI was a significant risk factor for disease-free survival [hazard ratio (HR): 7.051; 95% confidence interval (CI): 1.570-31.659; P=0.011] and overall survival (HR: 8.289; 95% CI: 1.036-66.307; P=0.046), even after adjustment for various factors. CONCLUSIONS: Adjuvant chemotherapy does not affect the prognosis of stage IB NSCLC, even in high-risk patients. Additionally, VPI is a strong prognostic factor of stage IB NSCLC.

Cross-Reactivity between Oak and Birch Pollens in Korean Tree Pollinosis.

Oak and birch trees belong to Fagales order. Specific IgE to pollen allergens of both trees are frequently found in Korea pollinosis patients. Oak trees which comprise 40% of forest area are common in Korea. However, birch trees are sparse. We compared the allergenicity of pollen extracts of white oak, sawtooth and Mongolian oaks which are prevalent species in Korea, with the pollen extract of birch. The cross-reactivity of four pollen extracts was examined with pooled sera of 12 patients by ELISA, immunoblotting and CAP inhibitions. A protein of 17 kDa, putatively homologous to a major birch allergen Bet v 1, displayed strong IgE reactivity from white oak and sawtooth oak pollen extract but not from Mongolian oak pollen. Notably, a 23-kDa protein from sawtooth and white oaks showed strong IgE reactivity and inhibited by Bet v 1. IgE binding to white oak was inhibited a maximum of 94.6% by white oak, 93.4% by sawtooth oak, 83.2% by Mongolian oak, and 68.8% by birch. Furthermore, sawtooth oak, white oak, and Mongolian oak extracts were able to inhibit up to 78.5%, 76.6% and 67.3% of IgE binding to birch extract, while birch extract itself inhibited up to 94.3%. Specific IgE to Bet v 1 was inhibited a maximum of 79.1% by sawtooth oak, 77.4% by white oak, and 72.7% by Mongolian oak, while 81.5% inhibition was shown by birch. Bet v 1 was able to partially inhibit its homologous molecules from sawtooth oak and white oak in immunoblotting. Birch pollen extract was found to be cross-reactive primarily with Bet v 1-homologous allergen from oak pollens in Korea pollinosis patients. Considering the sparseness of birch tree in Korea, oak, especially sawtooth oak may be the main cause of tree pollinosis in Korea, rather than birch.

Toxic and adjuvant effects of silica nanoparticles on ovalbumin-induced allergic airway inflammation in mice.

BACKGROUND: Silica nanoparticles (SNPs) can easily enter in respiratory system via inhalation because of their low molecular weight and ease of dispersion. Toxicity and adverse effects of SNPs vary according to the physical characteristics of the particle. METHODS: To evaluate the toxic and adjuvant effects of 3 types of SNPs in the airway system, six-week-old female BALB/c mice were intranasally administered 3 types of SNPs (spherical [S-SNP], mesoporous [M-SNP], and polyethylene glycol-conjugated [P-SNP]) alone or SNPs/ovalbumin (OVA), three times weekly for 2 weeks. Airway hyper-responsiveness (AHR), bronchoalveolar lavage fluid (BALF), cytokine levels, and histology of the lungs were analyzed. RESULTS: The S-SNPs/OVA group and M-SNPs/OVA group showed significant AHR, compared to the control group. Among all SNP-treated groups, the group administered SNPs/OVA showed greater inflammatory cell infiltration in BALF, extensive pathological changes, and higher cytokine levels (IL-5, IL-13, IL-1ß, and IFN-γ) than those administered SNPs alone or saline/OVA. CONCLUSION: Exposure to SNPs alone and SNPs/OVA induced toxicity in the respiratory system. SNPs alone showed significant toxic effects on the airway system. Meanwhile, SNPs/OVA exerted adjuvant effects to OVA of inducing allergic airway inflammation. In particular, M-SNPs showed the most severe airway inflammation in both direct toxicity and adjuvant effect assays. P-SNPs induced less inflammation than the other types of SNPs in both models.

A Six-Year Study on the Changes in Airborne Pollen Counts and Skin Positivity Rates in Korea: 2008-2013.

PURPOSE: The occurrence of pollen allergy is subject to exposure to pollen, which shows regional and temporal variations. We evaluated the changes in pollen counts and skin positivity rates for 6 years, and explored the correlation between their annual rates of change. MATERIALS AND METHODS: We assessed the number of pollen grains collected in Seoul, and retrospectively reviewed the results of 4442 skin-prick tests conducted at the Severance Hospital Allergy-Asthma Clinic from January 1, 2008 to December 31, 2013. RESULTS: For 6 years, the mean monthly total pollen count showed two peaks, one in May and the other in September. Pollen count for grasses also showed the same trend. The pollen counts for trees, grasses, and weeds changed annually, but the changes were not significant. The annual skin positivity rates in response to pollen from grasses and weeds increased significantly over the 6 years. Among trees, the skin positivity rates in response to pollen from walnut, popular, elm, and alder significantly increased over the 6 years. Further, there was a significant correlation between the annual rate of change in pollen count and the rate of change in skin positivity rate for oak and hop Japanese. CONCLUSION: The pollen counts and skin positivity rates should be monitored, as they have changed annually. Oak and hop Japanese, which showed a significant correlation with the annual rate of change in pollen count and the rate of change in skin positivity rate over the 6 years may be considered the major allergens in Korea.

Standardization of Weed Pollen Extracts, Japanese Hop and Mugwort, in Korea.

PURPOSE: Japanese hop (Humulus spp.) and mugwort (Artemisia spp.) are notable causes of autumn pollinosis in East Asia. However, Japanese hop and mugwort pollen extracts, which are widely used for the diagnosis, have not been standardized. This study was performed to standardize Japanese hop and mugwort pollen extracts. MATERIALS AND METHODS: Allergen extracts were prepared in a standardized way using locally collected Humulus japonicus and purchased Artemisia vulgaris pollens. The immunoglobulin E (IgE) reactivities of prepared extracts were compared with commercial extracts via IgE immunoblotting and inhibition analyses. Intradermal skin tests were performed to determine the bioequivalent allergy unit (BAU). RESULTS: The IgE reactive components of the extracts via IgE immunoblotting were similar to those of commercial extracts. A 11-kDa allergen showed the strongest IgE reactivity in Japanese hop, as did a 28-kDa allergen in mugwort pollen extracts. Allergenic potencies of the investigatory Japanese hop and mugwort extracts were essentially indistinguishable from the commercial ones. Sums of erythema of 50 mm by the intradermal skin test (ΣED50) were calculated to be 14.4th and 13.6th three-fold dilutions for Japanese hop and mugwort extracts, respectively. Therefore, the allergenic activity of the prepared extracts was 90827.4 BAU/mg for Japanese hop and 34412 BAU/mg for mugwort. CONCLUSION: We produced Japanese hop and mugwort pollen extracts using a standardized method. Standardized Japanese hop and mugwort pollen extracts will facilitate the production of improved diagnostic and immunotherapeutic reagents.

Clinical features of and genetic predisposition to drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a single Korean tertiary institution patients-investigating the relation between the HLA -B*4403 allele and lamotrigine.

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but fatal adverse mucocutaneous reactions to certain drugs. Recent studies suggest that ethnicity and genetic predisposition may play a crucial role in the manifestation of the reaction. In this study, we described the role of human leukocyte antigen (HLA)-B alleles in the development of clinical characteristics and treatment outcomes of SJS/TEN in a single Korean tertiary hospital. METHODS: We retrospectively reviewed the medical records (from March 1, 2010 to February 28, 2014) of 30 patients diagnosed with SJS and/or TEN. RESULTS: The main causative drugs were anticonvulsants (26.7 %) and allopurinol (26.7 %), followed by antibiotics (16.7 %), acetazolamide (10.0 %), acetaminophen (10.0 %), and herbal medication (6.7 %). The mean latencies of these drugs were variable. Liver damage was the most common symptom (observed in 63.3 % of the patients). Of the five patients with lamotrigine-induced SJS/TEN, three expressed the HLA-B*4403 allele (60.0 %). Of the seven patients with allopurinol-induced SJS/TEN, five expressed the HLA-B*5801 allele (71.4 %). CONCLUSIONS: The major SJS/TEN-inducing drugs were found to be allopurinol and anticonvulsants (such as lamotrigine). We speculated that Korean individuals expressing the HLA-B*4403 allele may be highly susceptible to lamotrigine-induced SJS/TEN.

Aqueous extract of Artemisia capillaris exerts hepatoprotective action in alcohol-pyrazole-fed rat model.

ETHNOPHARMACOLOGICAL 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 (10 mL/kg, twice per day) plus pyrazole (PRZ, 30 mg/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-ß) 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.

Artemisia capillaris extract protects against bile duct ligation-induced liver fibrosis in rats.

Artemisia capillaris has been widely used as a traditional herbal medicine in the treatment of liver diseases. However, no previous study has investigated whether A. capillaries alone is effective in treating pathological conditions associated with cholestatic liver injury. In the present study, we evaluated the anti-hepatofibrotic effects of A. capillaris (aqueous extract, WAC) in a bile duct ligation (BDL)-induced cholestatic fibrosis model. After BDL, rats were given WAC (25 or 50 mg/kg) or urosodeoxycholic acid (UDCA, 25 mg/kg) orally for 2 weeks (once per day). The serum cholestatic markers, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group, while administering WAC significantly reduced these alterations. Administering WAC also restored the BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAC treatment, and these changes were paralleled by the significantly suppressed expression of fibrogenic factors, including hepatic alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-ß). The beneficial effects of WAC administration are associated with antifibrotic properties via both upregulation of antioxidant activities and downregulation of ECM protein production in the rat BDL model.

Indirect moxibustion (CV4 and CV8) ameliorates chronic fatigue: a randomized, double-blind, controlled study.

OBJECTIVES: The antifatigue effect of indirect moxibustion and its antioxidant properties were investigated. SUBJECTS AND DESIGN: A randomized, double-blind, controlled clinical trial was performed with 44 patients who had idiopathic chronic fatigue. The subjects were treated with a placebo or moxibustion (indirect moxibustion on CV4 and CV8 3 times per week for 4 weeks), and their fatigue severity was monitored using a self-rating numeric scale (NRS) and a visual analog scale (VAS). Serum level of reactive oxygen species and malondialdehyde (MDA), total antioxidant capacity, the activity of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase and total glutathione content, were determined before initial moxibustion therapy and after the 12th moxibustion treatment. RESULTS: The moxibustion group had a significantly lower fatigue severity score compared to the control for both the NRS (p<0.05) and VAS scores (p<0.01). The level of serum MDA was significantly lower in the moxibustion group than in the placebo group (p<0.05), whereas glutathione reductase activity and total glutathione content increased significantly following moxibustion (p<0.05). CONCLUSIONS: The results provide clinical evidence for an antifatigue effect of indirect moxibustion at CV4 and CV8 and suggest that the effect is due to the antioxidant properties of moxibustion.

Aqueous extract of Artemisia iwayomogi Kitamura attenuates cholestatic liver fibrosis in a rat model of bile duct ligation.

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 50 mg/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 ß. 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.

Antioxidant effects of Panax ginseng C.A. Meyer in healthy subjects: a randomized, placebo-controlled clinical trial.

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 4 weeks. 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.

Herbal formula CGX ameliorates LPS/D-galactosamine-induced hepatitis.

CGX, a traditional herbal drug, has been prescribed for patients suffering from various liver diseases, including hepatitis B, alcoholic liver disease, and fatty liver. We investigated whether CGX has hepatoprotective effects against lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute liver injury and its underlying mechanism(s). Mice were administered CGX orally for 7 days prior to an injection of LPS (5 µg/kg)/D-GalN (700 mg/kg). Complete blood count, serum diagnostic markers, antioxidant activities, caspase activity, and histopathological examinations were conducted 8 h after the injection. To evaluate the immunological mechanism of CGX, serum TNF-α and IL-10 were investigated 1.5 h after LPS/D-GalN injection. CGX pretreatment (100, 200, and 400 mg/kg) inhibited the elevation of serum AST and ALT levels as well as histopathological alterations. Moreover, CGX pretreatment inhibited activation of caspase-3/7. CGX attenuated LPS/D-GalN-induced lipid peroxidation with concomitant improvement in total antioxidant activities (superoxide dismutase, catalase, and glutathione peroxidase). CGX elevated the antioxidant capacity of the liver in both the pathological and normal conditions. Furthermore, LPS/D-GalN-induced alterations of neutrophil and lymphocyte populations were ameliorated and serum TNF-α was decreased significantly by CGX. From these data we conclude that CGX protects the liver from LPS/D-GalN-induced hepatitis through antioxidant mechanisms as well as immune modulation.

Effects of Korean ginseng root extract on cisplatin-induced emesis in a rat-pica model.

In the present study, we investigate the effect of Korean ginseng root extract (KG) on cisplatin-induced pica in a rat model. Rats were treated with KG before (25, 50, and 100 mg/kg) or after (12.5, 25, and 50 mg/kg) a single intraperitoneal injection of cisplatin (7 and 6 mg/kg, respectively). We examined intake of kaolin and normal food as an indicator of the emetic stimulus every 24 h for 120 h. Changes in body weight, haematology and histopathology were additionally assessed. Pre-treatment with KG (25 and 50 mg/kg) significantly attenuated cisplatin-induced kaolin intake (24, 48, and 72 h) and markedly improved intake of normal food by rats at 48, 72, 96, and 120 h. Cisplatin-induced kaolin intake was markedly decreased upon post-treatment of rats with KG (12.5, 25, and 50 mg/kg) at 24 h. Notably, post-treatment with the lowest KG dose resulted in a significant anti-pica effect and improved food intake until 72 h. The magnitude of body weight reduction was significantly diminished in rats pre-treated/post-treated with 25, 50, and 12.5 mg/kg KG. The anti-pica effects of KG were further confirmed with haematological and histopathological findings. Our findings collectively indicate that KG improves the resistance of rats against emesis.

CGX, a traditional Korean medicine ameliorates concanavalin A-induced acute liver injury.

Concanavalin A (Con A)-induced acute liver injury model is well established as a model of T cell-mediated liver injury, in which T cells and NKT cells exert their cytotoxicity towards liver cells. In this study, we investigated the protective effects of CGX, a traditional Korean medicine against Con A-induced liver injury and its underlying mechanisms. After pretreatment with CGX (po, 50, 100 or 200 mg/kg) or distilled water once daily during 7 days, Con A (15 mg/kg) was injected intravenously. Thereafter serum level of AST and ALT, lipid peroxidation and cytokines in the liver tissue, and immune cell population in blood and the spleen were analyzed. CGX treatment reduced serum ALT, AST level in a dose-dependent manner. CGX treatment significantly decreased the lipid peroxidation and glutathione depletion in the liver tissue, and also lowered tissue levels of tumor necrotic factor-α and interferon-γ. CGX treatment attenuated the compositional alteration of Tc, Th, NKT, and B cells in blood as well as in the spleen. These results suggest that CGX has hepatoprotective property against Con A-induced liver injury through antioxidant action and immune regulation.

Metabolite profiling of doenjang, fermented soybean paste, during fermentation.

BACKGROUND: A fermented soybean paste known as doenjang is a traditional fermented food that is widely consumed in Korea. The quality of doenjang varies considerably by its basic ingredients, species of microflora, and fermentation process. The classification of predefined metabolites (e.g. amino acids, organic acids, sugars and sugar derivatives, and fatty acids) in doenjang samples according to fermentation was performed by using GC-FID and GC-MS data sets with the application of a multivariate statistical method. RESULTS: The predominantly produced amino acids included alanine, valine, leucine, isoleucine, proline, glutamine, phenylalanine and lysine, showing remarkable increases in amounts during the later stages of fermentation. Carbonic acid, citric acid, lactic acid and pyrogultamic acid were identified as the major organic acids. Significant amounts of erythrose, xylitol, inositol and mannitol were detected during fermentation. Regarding fatty acids, relatively higher amounts of palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid were found in the doenjang at each fermentation time point. Principal component analysis (PCA) successfully demonstrated changes in composition patterns as well as differences in non-volatile metabolites according to fermentation period. CONCLUSION: A set of metabolites could be determined representing the quality of doenjang during fermentation, and which might also be correlated with taste ingredients, flavour, nutrition, and physiology activities that are claimed to be dependent on the quality control of commercial doenjang.

Safety of the traditional Korean herbal medicine CGX: a 6-month repeated-dose study in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: CGX is a traditional Korean herbal medicine used to treat chronic liver diseases. AIM OF STUDY: The purpose of this study was to evaluate the pharmaceutical safety of hepatoprotective herbal medicine, CGX via systemic 6-month repeated dose toxicity study in SD rats. MATERIALS AND METHODS: Male and female SD rats were administered CGX for 6 months (0, 100, 200, or 400 mg kg(-1), respectively). The rats were visually inspected for changes in behavior, body weight, food and water consumption, and appearance during the experiment period. At the end of the experiment, urine, hematological, biochemical analysis, and histopathological examination were carried out. RESULTS: No drug-induced abnormalities were found as clinical signs or in the histopathology, hematology, blood biochemistry, and urinalysis results for any administered doses of CGX. CONCLUSION: The results suggest that CGX is safe and could be considered as an effective and prospective herbal formulation in clinical applications with a wide therapeutic index.