New insight of chemical constituents in Persea americana fruit against obesity via integrated pharmacology.

Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti-OB efficacy of the non-fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein-protein interaction (PPI), PAF-signaling pathways-targets-compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti-OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1-gamma-tocopherol, PPARA-fucosterol, PPARD-stigmasterol, (PPARG)-fucosterol, (NR1H3)-campesterol, and ILK-alpha-tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB.

The convergent application of metabolites from Avena sativa and gut microbiota to ameliorate non-alcoholic fatty liver disease: a network pharmacology study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a serious public health issue globally, currently, the treatment of NAFLD lies still in the labyrinth. In the inchoate stage, the combinatorial application of food regimen and favorable gut microbiota (GM) are considered as an alternative therapeutic. Accordingly, we integrated secondary metabolites (SMs) from GM and Avena sativa (AS) known as potent dietary grain to identify the combinatorial efficacy through network pharmacology. METHODS: We browsed the SMs of AS via Natural Product Activity & Species Source (NPASS) database and SMs of GM were retrieved by gutMGene database. Then, specific intersecting targets were identified from targets related to SMs of AS and GM. The final targets were selected on NAFLD-related targets, which was considered as crucial targets. The protein-protein interaction (PPI) networks and bubble chart analysis to identify a hub target and a key signaling pathway were conducted, respectively. In parallel, we analyzed the relationship of GM or AS─a key signaling pathway─targets─SMs (GASTM) by merging the five components via RPackage. We identified key SMs on a key signaling pathway via molecular docking assay (MDA). Finally, the identified key SMs were verified the physicochemical properties and toxicity in silico platform. RESULTS: The final 16 targets were regarded as critical proteins against NAFLD, and Vascular Endothelial Growth Factor A (VEGFA) was a key target in PPI network analysis. The PI3K-Akt signaling pathway was the uppermost mechanism associated with VEGFA as an antagonistic mode. GASTM networks represented 122 nodes (60 GM, AS, PI3K-Akt signaling pathway, 4 targets, and 56 SMs) and 154 edges. The VEGFA-myricetin, or quercetin, GSK3B-myricetin, IL2-diosgenin complexes formed the most stable conformation, the three ligands were derived from GM. Conversely, NR4A1-vestitol formed stable conformation with the highest affinity, and the vestitol was obtained from AS. The given four SMs were no hurdles to develop into drugs devoid of its toxicity. CONCLUSION: In conclusion, we show that combinatorial application of AS and GM might be exerted to the potent synergistic effects against NAFLD, dampening PI3K-Akt signaling pathway. This work provides the importance of dietary strategy and beneficial GM on NAFLD, a data mining basis for further explicating the SMs and pharmacological mechanisms of combinatorial application (AS and GM) against NAFLD.

Effect of Korean Red Ginseng on metabolic syndrome.

Metabolic syndrome (MS) refers to a clustering of at least three of the following medical conditions: high blood pressure, abdominal obesity, hyperglycemia, low high-density lipoprotein level, and high serum triglycerides. MS is related to a wide range of diseases which includes obesity, diabetes, insulin resistance, cardiovascular disease, dyslipidemia, or non-alcoholic fatty liver disease. There remains an ongoing need for improved treatment strategies for MS. The most important risk factors are dietary pattern, genetics, old age, lack of exercise, disrupted biology, medication usage, and excessive alcohol consumption, but pathophysiology of MS has not been completely identified. Korean Red Ginseng (KRG) refers to steamed/dried ginseng, traditionally associated with beneficial effects such as anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. KRG has been often used in traditional medicine to treat multiple metabolic conditions. This paper summarizes the effects of KRG in MS and related diseases such as obesity, cardiovascular disease, insulin resistance, diabetes, dyslipidemia, or non-alcoholic fatty liver disease based on experimental research and clinical studies.

The Role of the Gut Microbiome in Liver Cirrhosis Treatment.

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson's disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for Helicobacter pylori infection.

AIM: To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for Helicobacter pylori infection. METHODS: This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with H. pylori infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of H. pylori. RESULTS: In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, P = .37), modified intention-to-treat (96.2% vs. 96%, P > .99), and per-protocol (96.2% vs. 96.9%, P > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies. CONCLUSION: Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the H. pylori infection in regions with high clarithromycin and metronidazole resistance.

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study.

BACKGROUND AND AIMS: Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease. METHODS: Liver cirrhosis patients with Child-Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months. RESULTS: A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score (p = 0.009) and CP score (p = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221-0.684, p < 0.001). CONCLUSION: Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.

Effects of vitamin D supplements in patients with chronic hepatitis C: a randomized, multi-center, open label study.

BACKGROUND/AIMS: We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC). METHODS: Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). RESULTS: One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverse effects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). CONCLUSION: Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.

Gut microbiota: novel therapeutic target for nonalcoholic fatty liver disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide with a prevalence of 20-33%. NAFLD may progress to fibrosis, compensated cirrhosis, advanced cirrhosis, or hepatocellular carcinoma. Despite the increasing prevalence of NAFLD, definitive medical treatment has not been established, with the exception of lifestyle modification with exercise. Because of the direct connection via portal vein between the intestines and the liver (gut-gut microbiota-liver axis), gut microbiota and associated dysbiosis have been known as regulators in the pathophysiology of NAFLD. Area covered: New therapeutic approaches for modulation of gut microbiota have been proposed and the effectiveness of new therapies including probiotics, prebiotics, synbiotics, bile acid regulation, absorbent, and fecal microbiota transplantation have been demonstrated in recent several studies. This review focuses on the available evidences for new therapies modulating gut microbiota in the management and the prevention of NAFLD. Expert commentary: Gut-gut microbiota-liver axis may play an important role in the etiology of many liver diseases, including NAFLD. It is logical to seek the manipulation of this axis, and further studies are required to understand the underlying precise mechanisms of microbiota-modulation on NAFLD.

Effects of branched-chain amino acids (BCAAs) on the progression of advanced liver disease: A Korean nationwide, multicenter, retrospective, observational, cohort study.

Evidence of the potential benefits of long-term oral branched-chain amino acid (BCAA) supplementation in reducing the severity of liver disease is limited.Patients who were diagnosed with liver cirrhosis with a Child-Pugh (CP) score of 8-10 were included. The BCAA group consumed BCAAs daily for at least 6 months, and the control group consumed a diet without BCAA. We analyzed the improvements based on the model for end-stage liver disease (MELD) score, CP score, incidence of cirrhosis-related complications, and event-free survival over 2 years. Among the 867 recruited patients, 307 (166 in the BCAA group and 141 in the control group) were analyzed. The BCAA group was divided into 3 subgroups, whose patients consumed 4.15 g, 8.3 g, or 12.45 g of BCAAs daily for the analysis. There were significant differences in the CP score, albumin, and hepatic encephalopathy between the 2 groups at baseline. After matching the propensity scores, we analyzed patients in the BCAA-12.45 g group (12.45 g of BCAAs daily, n = 41) and matched control group (n = 41). The MELD score significantly improved in the BCCA-12.45 g group compared to the matched control group (P = .004). The changes in the serum bilirubin level (P = .014) and CP score (P = .033) over time also differed significantly between the 2 groups. The incidence rates of cirrhosis-related complications (P = .973) and development of hepatocellular carcinoma (2 cases each) did not differ significantly between the 2 groups.Long-term oral BCAA supplementation has beneficial effects in patients with advanced liver cirrhosis. A further large-scale prospective study is needed to delineate these beneficial effects.

Effects of probiotics (cultured Lactobacillus subtilis/Streptococcus faecium) in the treatment of alcoholic hepatitis: randomized-controlled multicenter study.

BACKGROUND: Probiotics might reduce gut-derived microbial lipopolysaccharide (LPS) by restoring bowel flora in patients with alcoholic hepatitis (AH). We evaluated the therapeutic effects of probiotics in patients with AH. PATIENTS AND METHODS: Between September 2010 and April 2012, 117 patients (probiotics 60 and placebo 57) were prospectively randomized to receive the 7 days of cultured Lactobacillus subtilis/Streptococcus faecium (1500 mg/day) or placebo. All patients were hospitalized and were not permitted to consume alcohol for the 7 days of the study. Liver function test, proinflammatory cytokines, LPS, and colony-forming units by stool culture were examined and compared after therapy. RESULTS: In both groups, the mean levels of aspartate aminotransferase/alanine aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin, and prothrombin time were significantly improved after 7 days of abstinence. In the probiotics group (baseline and after), albumin (3.5 ± 0.7 and 3.7 ± 0.6 g/dl, P=0.038) and tumor necrosis factor-α (121 ± 244 and 71 ± 123 pg/ml, P=0.047) showed differences. In addition, the number of colony-forming units of Escherichia coli was significantly reduced (435 ± 287 and 168 ± 210, P=0.002). In the placebo group, the level of LPS (1.7 ± 2.8 and 2.0 ± 2.7 EU/ml) was significantly increased. In the intergroup comparison, significant differences in the levels of tumor necrosis factor-α (P=0.042) and LPS (P=0.028) were observed between the groups. CONCLUSION: Immediate abstinence is the most important treatment for patients with AH. In addition, 7 days of oral supplementation with cultured L. subtilis/S. faecium was associated with restoration of bowel flora and improvement of LPS in patients with AH.

Probiotics (Lactobacillus rhamnosus R0011 and acidophilus R0052) reduce the expression of toll-like receptor 4 in mice with alcoholic liver disease.

OBJECTIVE: The role of lipopolysaccharide (LPS) and toll-like receptor 4 (TLR 4) in the pathogenesis of alcoholic liver disease (ALD) has been widely established. We evaluated the biological effects of probiotics (Lactobacillus rhamnosus R0011 and acidophilus R0052), KRG (Korea red ginseng), and urushiol (Rhus verniciflua Stokes) on ALD, including their effects on normal and high-fat diet in mice. METHODS: One hundred C57BL/6 mice were classified into normal (N) and high-fat diet (H) groups. Each group was divided into 5 sub-groups: control, alcohol, alcohol+probiotics, alcohol+KRG, and alcohol+urushiol. A liver function test, histology, electron-microscopy, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, and IL-10, and TLR 4 were evaluated and compared. RESULTS: In the N group, probiotics, KRG, and urushiol significantly reduced levels of TNF-α (12.3±5.1, 13.4±3.9, and 12.1±4.3 vs. 27.9±15.2 pg/mL) and IL-1ß (108.4±39.4, 75.0±51.0, and 101.1±26.8 vs. 162.4±37.5 pg/mL), which were increased by alcohol. Alcohol-induced TLR 4 expression was reduced by probiotics and urushiol (0.7±0.2, and 0.8±0.1 vs. 1.0±0.3, p<0.001). In the H group, IL-10 was significantly increased by probiotics and KRG, compared with alcohol (25.3±15.6 and 20.4±6.2 vs. 7.6±5.6 pg/mL) and TLR 4 expression was reduced by probiotics (0.8±0.2 vs. 1.0±0.3, p = 0.007). CONCLUSIONS: Alcohol-induced TLR 4 expression was down-regulated by probiotics in the normal and high-fat diet groups. Probiotics, KRG, and urushiol might be effective in the treatment of ALD by regulating the gut-liver axis.

Associations between intakes of individual nutrients or whole food groups and non-alcoholic fatty liver disease among Korean adults.

BACKGROUND AND AIM: Dietary factors are closely associated with the risk of non-alcoholic fatty liver disease (NAFLD). Asian and Western diets differ in energy-nutrient composition, fatty-acid composition, and main nutritional sources; therefore, the implications would be limited if the Western-oriented study results were applied to Asian patients. We aimed to identify the nutrient and food group intakes of a typical Asian diet and assess their effects on NAFLD risk. METHODS: In total, 348 subjects were recruited from 5 participating hospitals. Information on sociodemographic characteristics and health-related behaviors were obtained through face-to-face interviews. NAFLD was diagnosed by ultrasound. Dietary intakes were assessed with a 24-h recall applying a multiple-pass approach and 4-day food records that included 1 or 2 weekend days. RESULTS: There were no significant differences in health-related behaviors between the cases and controls except for smoking behavior. The cases had elevated triacylglycerol, fasting glucose, and low-density lipoprotein cholesterol levels compared with the controls. In men, after adjusting for variables, low intakes of vitamin C (odds ratio [OR], 4.23), vitamin K (OR, 3.93), folate (OR, 3.37), omega-3 fatty acids (OR, 2.16), and nuts and seeds (OR, 3.66) were associated with a significantly higher risk for developing NAFLD. In women, vitamin K (OR, 2.54) and vegetable (OR, 4.11) intakes showed a significant beneficial effect for lowering NAFLD risk. CONCLUSIONS: Adequate intakes of vitamin C, vitamin K, folate, omega-3 fatty acids, nuts and seeds, and vegetables may help in preventing NAFLD in Korean adults.

Catheter-free method is sufficient for preparation for transnasal endoscopy: randomized controlled trial.

BACKGROUND AND AIM: Although transnasal endoscopy (TNE) is generally a comfortable and safe procedure, it has some disadvantages, such as complicated preprocessing and occasional repulsion reaction during catheterization. In an attempt to simplify the preprocessing method, the efficacy of a catheter-free method in which a catheter is not inserted into the nasal cavity was assessed. METHODS: The present study was a prospective, open-label, single-center, randomized controlled study with parallel assignment allocation 1:1. Between March 2009 and August 2009, a total of 93 TNE-naïve patients were enrolled and randomized. Patients were prospectively randomized into two groups (catheter-free vs catheter-insertion method). Patients who prepared according to the catheter-free method and who were unsuccessful underwent the catheter-insertion method. Clinical characteristics, success rate, complications, vital signs, acceptability, and tolerability were assessed and compared. RESULTS: Success rates of the catheter-free and catheter-insertion methods were 88% (n=44) and 88% (n=38) (P>0.05), respectively. Causes of failure in the catheter-free method included severe rhinalgia (n=1, 2%) and narrowing of the nasal cavity (n=5, 10%). Causes of failure in the catheter-insertion method included narrowing of the nasal cavity (n=5, 11%). Six patients whose TNE failed with the catheter-free method also experienced failed TNE with the catheter-insertion method. There were no statistical differences in vital signs, acceptability, and tolerability. CONCLUSION: The catheter-free method is sufficient for preparation for TNE. The success rate of TNE depends more on the structure of the nasal cavity than the preprocessing method.

Anti-oxidant and natural killer cell activity of Korean red ginseng (Panax ginseng) and urushiol (Rhus vernicifera Stokes) on non-alcoholic fatty liver disease of rat.

Anti-oxidative and immunologic effects of the Korea red ginseng (KRG; Panax ginseng) and urushiol (Rhus vernicifera Stokes) on non-alcoholic fatty liver disease (NAFLD) were evaluated. Forty-five rats (five Long-Evans Tokushima Otsuka and 40 Otsuka Long-Evans Tokushima Fatty [OLETF] rats) received chew diets for 10months; after this period. The OLETF rats were divided into the following four groups according to diet for 2months: NAFLD (chew), KRG (chew+KRG [200mg/kg/day]), urushiol (chew+urushiol [0.5mg/kg/day]), and ursodeoxycholic acid (UDCA) (chew+UDCA [15mg/kg/day]) groups. Liver function, lipid profiles and anti-oxidant activity of liver and serum, natural killer (NK) cell activity, and pathology were compared. In KRG and urushiol groups, the level of serum triglyceride ([302.0±70.4 and 275.2±63.8] vs. 527.7±153.3mg/dL) were lower compared with that of NAFLD group (p<0.05). The levels of HDL-cholesterol (liver tissue: [4.8±0.2 and 4.8±0.5] vs. 4.2±0.2mg/g) and NK cell activity ([3485±910 and 3559±910] vs. 2486±619 counts) were significantly higher than those of the NAFLD group (p<0.001). Inflammation with neutrophil infiltration was observed in only two rats in the NAFLD group. These results suggest that 2months of oral KRG or urushiol administration improves lipid profiles and stimulates NK cell activity, while inhibiting steatohepatitis in OLEFT rats.

Drug-induced liver injury: present and future.

Liver injury due to prescription and nonprescription medications is a growing medical, scientific, and public health problem. Worldwide, the estimated annual incidence rate of drug-induced liver injury (DILI) is 13.9-24.0 per 100,000 inhabitants. DILI is one of the leading causes of acute liver failure in the US. In Korea, the annual extrapolated incidence of cases hospitalized at university hospital is 12/100,000 persons/year. Most cases of DILI are the result of idiosyncratic metabolic responses or unexpected reactions to medication. There is marked geographic variation in relevant agents; antibiotics, anticonvulsants, and psychotropic drugs are the most common offending agents in the West, whereas in Asia, 'herbs' and 'health foods or dietary supplements' are more common. Different medical circumstances also cause discrepancy in definition and classification of DILI between West and Asia. In the concern of causality assessment, the application of the Roussel Uclaf Causality Assessment Method (RUCAM) scale frequently undercounts the cases caused by 'herbs' due to a lack of previous information and incompatible time criteria. Therefore, a more objective and reproducible tool that could be used for the diagnosis of DILI caused by 'herbs' is needed in Asia. In addition, a reporting system similar to the Drug-Induced Liver Injury Network (DILIN) in the US should be established as soon as possible in Asia.

A prospective nationwide study of drug-induced liver injury in Korea.

OBJECTIVES: To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea. METHODS: From May 2005 to May 2007, cases of DILI (alanine transferase > 3 × upper normal limit or total bilirubin > 2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used. RESULTS: A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included "herbal medications" (102, 27.5%), "prescription or non-prescription medications" (101, 27.3%), "health foods or dietary supplements" (51, 13.7%), "medicinal herbs or plants" (35, 9.4%), "folk remedies" (32, 8.6%), "combined" (30, 8.2%), "herbal preparations" (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hy's law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM. CONCLUSIONS: DILI appears to be a highly relevant health problem in Korea. "Herbal medications" are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria.

Antibacterial effects of the urushiol component in the sap of the lacquer tree (Rhus verniciflua Stokes) on Helicobacter pylori.

BACKGROUND: Urushiol is a major component of the lacquer tree which has been used as a folk remedy for the relief of abdominal discomfort in Korea. The aim of this study was to evaluate the antibacterial effects of the urushiol on Helicobacter pylori. MATERIALS AND METHODS: Monomer and 2-4 polymer urushiol were used. In the in vitro study, pH- and concentration-dependent antibacterial activity of the urushiol against H. pylori were investigated. In addition, the serial morphological effects of urushiol on H. pylori were examined by electron microscopy. In vivo animal study was performed for the safety, eradication rate, and the effect on gastritis of urushiol. The expression of pro-inflammatory cytokines was checked. RESULTS: All strains survived within a pH 6.0-9.0. The minimal inhibitory concentrations of the extract against strains ranged 0.064-0.256 mg/mL. Urushiol caused separation of the membrane and lysis of H. pylori within 10 minutes. Urushiol (0.128 mg/mL × 7 days) did not cause complications on mice. The eradication rates were 33% in the urushiol monotherapy, 75% in the triple therapy (omeprazole + clarithromycin + metronidazole), and 100% in the urushiol + triple therapy, respectively. H. pylori-induced gastritis was not changed by urushiol but reduced by eradication. Only the expression of interleukin-1ß in the gastric tissue was significantly increased by H. pylori infection and reduced by the urushiol and H. pylori eradication (p = .014). CONCLUSIONS: The urushiol has an antibacterial effect against H. pylori infection and can be used safely for H. pylori eradication in a mouse model.