Plant phenotype relationship corpus for biomedical relationships between plants and phenotypes.

Medicinal plants have demonstrated therapeutic potential for applicability for a wide range of observable characteristics in the human body, known as "phenotype," and have been considered favorably in clinical treatment. With an ever increasing interest in plants, many researchers have attempted to extract meaningful information by identifying relationships between plants and phenotypes from the existing literature. Although natural language processing (NLP) aims to extract useful information from unstructured textual data, there is no appropriate corpus available to train and evaluate the NLP model for plants and phenotypes. Therefore, in the present study, we have presented the plant-phenotype relationship (PPR) corpus, a high-quality resource that supports the development of various NLP fields; it includes information derived from 600 PubMed abstracts corresponding to 5,668 plant and 11,282 phenotype entities, and demonstrates a total of 9,709 relationships. We have also described benchmark results through named entity recognition and relation extraction systems to verify the quality of our data and to show the significant performance of NLP tasks in the PPR test set.

Characteristics and phylogenetic analysis of the complete chloroplast genome of Paeonia japonica (Paeoniaceae).

Paeonia japonica, distributed throughout Asia, is a traditional medicinal herb in Korea, with many potential beneficial effects including pain-relieving, anti-inflammatory, and anti-cancer activities. Despite its high pharmacological value, the genetic information on Paeonia japonica remains limited. In this study, the chloroplast genome of P. japonica was sequenced using next-generation sequencing (NGS) technology and genome and phylogeny were analyzed using multiple tools. The chloroplast genome of P. japonica was 152,731 bp in length with an inverted repeat region of 26,656 bp, including a large single-copy region of 84,389 bp and a small single copy region of 17,030 bp. The P. japonica chloroplast genome included 113 genes comprising 80 protein-coding genes, 27 tRNA, and 5 rRNA genes. Phylogenetic analysis indicated that P. japonica and P. obovata share a close evolutionary relationship.

Antimicrobial Resistance and Molecular Analysis of Staphylococcus aureus in Staphylococcal Scalded Skin Syndrome among Children in Korea.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) is a skin disease characterized by blistering and desquamation caused by exfoliative toxins (ETs) of Staphylococcus aureus (S. aureus). Although many countries show predominance of methicillin-susceptible S. aureus (MSSA), cases of methicillin-resistant S. aureus (MRSA) have been reported. METHODS: Twenty-six children aged <15 years diagnosed with SSSS from January 2010 to December 2017 from three hospitals were included. S. aureus isolates from cases were analyzed for multilocus sequence types and ETs. Medical records were reviewed for clinical characteristics, treatment, and antimicrobial susceptibility patterns of S. aureus. RESULTS: Among the 26 cases, mean age was 2.3 years. According to skin manifestations patients were classified as generalized (n = 10, 38.5%), intermediate (n = 11, 42.3%), and abortive (n = 5, 19.2%). Among all cases, 96.2% (25/26) were due to MRSA and the macrolide-resistance rate was 92.3% (24/26). ST89 (n = 21, 80.8%) was the most prevalent clone, followed by single clones of ST1, ST5, ST72, ST121, and ST1507. The eta gene was detected in one (3.8%) isolate which was MSSA. The etb gene was detected in 14 (53.8%) isolates, all of which were ST89. Nafcillin or first-generation cephalosporin was most commonly prescribed (n=20, 76.9%). Vancomycin was administered in four patients (15.4%) and clindamycin in nine patients (34.6%). Among MRSA cases, there was no difference in duration of treatment when comparing the use of antimicrobials to which the causative bacteria were susceptible or non-susceptible (9.75 vs. 8.07 days, P > 0.05). CONCLUSION: S. aureus isolated from children with SSSS in Korea demonstrated a high prevalence of methicillin-resistant ST89 clones that harbored the etb gene. The predominance of MRSA suggests that antibiotics to which MRSA are susceptible may be considered for empirical antibiotic treatment in children with SSSS in Korea. Further studies on the role and effectiveness of systemic antibiotics in SSSS are warranted.

Effects of healthcare interventions on psychosocial factors of patients with multimorbidity: A systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis was conducted to assess the types of healthcare intervention programs offered to patients with multimorbidity and their effects on key psychosocial factors. METHODS: For this systematic review and meta-analysis, we searched databases like Cochrane Library, PubMed, Embase, CINAHL RISS, KISS, etc. for studies published between January 1, 2009, and April 30, 2019. In total, 8,248 studies in English or Korean were reviewed. We included only randomized controlled trials or quasi-experimental studies that applied healthcare interventions and had major effects on the psychosocial factors in adult patients with multimorbidity. Methodological quality was assessed using Cochrane collaboration risk of bias tool. Meta-analysis was performed using the Review Manager 5.3 version to estimate the effect size. RESULTS: We identified six randomized controlled trials and 1446 subjects were enrolled. The results reveal that healthcare interventions have an effect on self-rated health (SMD = 0.53 95 % CI: 0.26, 0.79, p < .001), reducing anxiety (SMD = -0.19 95 % CI: -0.36, -0.01, p = .030) and depression (SMD = -0.27 95 % CI: -0.44, -0.10, p = .002), and improving self-efficacy (SMD = 0.21 95 % CI: 0.06, 0.35, p = .005) for patients with multimorbidity. However, there was no significant effect on quality of life. CONCLUSION: Healthcare interventions had significant positive effects on self-rated health, anxiety, depression, and self-efficacy of patients with multimorbidity. These results are expected to serve as basic data for the development of a community-based integrated healthcare intervention program and health policy, especially for the vulnerable older population with multimorbidity.

White Ginseng Ameliorates Depressive Behavior and Increases Hippocampal 5-HT Level in the Stressed Ovariectomized Rats.

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.

Water Extract of Acori Graminei Rhizoma Attenuates Features of Rheumatoid Arthritis in DBA/1 Mice.

The dry rhizome of Acorus gramineus Solander, known as Acori Graminei Rhizoma, is used to treat dementia, stroke, eczema, and indigestion in traditional Chinese medicine, traditional Korean medicine, and traditional Japanese Kampo medicine. Previous studies have reported that Acori Graminei Rhizoma extract ameliorated cognitive impairment in Aß1-42 injected mice. However, the effect of Acori Graminei Rhizoma on type II collagen induced arthritis (CIA) has not been elucidated. Thus, we evaluated the water extract of Acori Graminei Rhizoma (WAG) in CIA mice models. Male DBA/1 mice were separated into five groups (NOR; n=10, CON; n=10, CIA + methotrexate (MTX); n=10, CIA + 100 mg/kg WAG; n=10, CIA + 500 mg/kg WAG; n=10). CIA was induced by injecting the mice with bovine type II collagen, after which the mice were treated with WAG and/or MTX. Hematological parameters and liver and kidney serum toxicity markers were analyzed. Further, serum levels of interleukin (IL)-6, TNF-α, and type II collagen IgG were analyzed via enzyme-linked immunosorbent assay (ELISA). Treatment with 500 mg/kg WAG decreased serum levels of IL-6, TNF-α, and collagen IgG in a CIA model. Moreover, WAG treatment decreased CIA-induced swelling of mouse hind legs, infiltration of inflammatory cells into the synovial membrane, and blood neutrophil levels. WAG administration did not influence hematological parameters or kidneys and liver toxicity markers. WAG may be used to treat arthritis by reducing the inflammation indicators. However, further experiments are required to determine how WAG affects inflammation mechanisms in vitro and in vivo.

Hyperbaric oxygen therapy for pyoderma gangrenosum associated with ulcerative colitis.

Pyoderma gangrenosum (PG), an ulcerating skin condition, is rare in patients with ulcerative colitis (UC). We report a case of successful treatment of PG in a patient with UC using hyperbaric oxygen therapy (HBOT). The patient had UC that was in remission following treatment with mesalazine and azathioprine therapy. After visiting an orthopedic clinic, the patient opted for treatment with antibiotics and daily dressing of the ulcerative skin lesions, while azathioprine was discontinued. However, the lesions did not improve. Two months later, the patient visited a dermatologist who diagnosed the lesions as PG, and he was admitted to our unit. Surgical debridement and HBOT were performed by a plastic surgeon in the emergency department. After 3 months of HBOT and topical treatment, the patient's PG completely resolved. His UC was still in remission with mesalazine alone. HBOT may be an effective and safe alternative treatment for PG associated with UC, particularly in patients in whom anti-tumor necrosis factor agents are unnecessary.

Radiologic findings as a determinant and no effect of macrolide resistance on clinical course of Mycoplasma pneumoniae pneumonia.

BACKGROUND: With the emergence of macrolide resistance, concerns about the efficacy of macrolides for the treatment of Mycoplasma pneumoniae (MP) pneumonia in children have been raised. This study aimed to determine the effect of macrolide resistance on the outcome of children who were hospitalized with MP pneumonia. METHODS: Between 2010 and 2015, we performed culture of MP from nasopharyngeal samples obtained from children who were hospitalized with pneumonia at five hospitals in Korea. Macrolide resistance was determined by the analysis of 23S rRNA gene transition and the minimal inhibitory concentrations of four macrolides. Medical records were reviewed to analyze the clinical response to treatment with macrolides. RESULTS: MP was detected in 116 (4.8%) of the 2436 children with pneumonia. MP pneumonia was prevalent in 2011 and 2015. Of the 116 patients with MP pneumonia, 82 (70.7%) were macrolide-resistant. There were no differences in the age distribution, total duration of fever, and chest x-ray patterns between the macrolide-susceptible and macrolide-resistant groups. After macrolide initiation, mean days to defervescence were longer in the macrolide-resistant group than in macrolide-susceptible group (5.7 days vs. 4.1 days, P = 0.021). However, logistic regression analysis revealed that the presence of extrapulmonary signs (P = 0.039), homogeneous lobar consolidation (P = 0.004), or parapneumonic effusion (P < 0.001) were associated with fever duration of ≥7 days after the initiation of macrolides, regardless of macrolide resistance. CONCLUSIONS: This study demonstrated that fever duration in MP pneumonia was determined by the radiologic findings of chest x-ray, not by the presence of macrolide resistance. The results highlight the need for future studies to assess therapeutic benefit from macrolides in the treatment of children with MP pneumonia.

Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea.

BACKGROUND: This study was performed to assess the serotype distribution and antibiotic nonsusceptibility of pneumococcal carriage isolates from children in Korea following the introduction of extended-valency pneumococcal conjugate vaccines (PCVs). METHODS: From April to June 2014, nasopharyngeal swabs were collected from children who were attending daycare centers in Korea. The collection was conducted in accordance with the World Health Organization Pneumococcal Carriage Working Group standards. Isolates were identified based on colony morphology, the presence of alpha-hemolysis, and inhibition by optochin test. Serotype was determined by Quellung reaction and sequencing analysis (for serogroup 6). The E-test was performed to determine antibiotic susceptibility. RESULTS: A total of 267 pneumococcal isolates were collected from 734 children. Non-PCV13 serotypes accounted for 88.3% and 23A (12.6%), 15B (10.4%), and 15C (9.5%) were most common. Younger age was associated with higher carriage (65.6% vs. 31.2%, P<0.001), while completion of PCV vaccination was associated with lower carriage caused by PCV13 serotypes (7.4% vs. 20.8%, P=0.007). Overall, nonsusceptibility rates were 86.0% to penicillin and 90.5% to erythromycin, with a multidrug resistance rate of 81.5%. Among penicillin-nonsusceptible isolates, those caused by PCV13 serotypes were 11% and non-PCV13 serotypes were 89%. Frequent non-PCV13 serotypes (23A, 15B, and 15C) were all nonsusceptible to both penicillin and erythromycin except one. CONCLUSION: High rates of carriage caused by non-PCV13 serotypes such as 23A, 15B, and 15C that show nonsusceptibilities to penicillin and erythromycin were noted following the introduction of extended-valency PCVs in Korea.

Evaluation of Anti-Inflammatory Potential of the New Ganghwaljetongyeum on Adjuvant-Induced Inflammatory Arthritis in Rats.

Ganghwaljetongyeum (GHJTY) has been used as a standard treatment for arthritis for approximately 15 years at the Korean Medicine Hospital of Dongshin University. GHJTY is composed of 18 medicinal herbs, of which five primary herbs were selected and named new Ganghwaljetongyeum (N-GHJTY). The purpose of the present study was to observe the effect of N-GHJTY on arthritis and to determine its mechanism of action. After confirming arthritis induction using complete Freund's adjuvant (CFA) in rats, N-GHJTY (62.5, 125, and 250 mg/kg/day) was administered once a day for 10 days. In order to determine pathological changes, edema of the paws and weight were measured before and for 10 days after N-GHJTY administration. Cytokine (TNF-α, IL-1ß, and IL-6) levels and histopathological lesions in the knee joint were also examined. Edema in the paw and knee joint of N-GHJTY-treated rats was significantly decreased at 6, 8, and 10 days after administration, compared to that in the CFA-control group, while weight consistently increased. Rats in N-GHJTY-treated groups also recovered from the CFA-induced pathological changes and showed a significant decline in cytokine levels. Taken together, our results showed that N-GHJTY administration was effective in inhibiting CFA-induced arthritis via anti-inflammatory effects while promoting cartilage recovery by controlling cytokine levels.

HerDing: herb recommendation system to treat diseases using genes and chemicals.

In recent years, herbs have been researched for new drug candidates because they have a long empirical history of treating diseases and are relatively free from side effects. Studies to scientifically prove the medical efficacy of herbs for target diseases often spend a considerable amount of time and effort in choosing candidate herbs and in performing experiments to measure changes of marker genes when treating herbs. A computational approach to recommend herbs for treating diseases might be helpful to promote efficiency in the early stage of such studies. Although several databases related to traditional Chinese medicine have been already developed, there is no specialized Web tool yet recommending herbs to treat diseases based on disease-related genes. Therefore, we developed a novel search engine, HerDing, focused on retrieving candidate herb-related information with user search terms (a list of genes, a disease name, a chemical name or an herb name). HerDing was built by integrating public databases and by applying a text-mining method. The HerDing website is free and open to all users, and there is no login requirement. Database URL: http://combio.gist.ac.kr/herding.

Receptor-Meditated Endocytosis by Hyaluronic Acid@Superparamagnetic Nanovetor for Targeting of CD44-Overexpressing Tumor Cells.

The present report proposes a more rational hyaluronic acid (HA) conjugation protocol that can be used to modify the surface of the superparamagnetic iron oxide nanoparticles (SPIONs) by covalently binding the targeting molecules (HA) with glutamic acid as a molecular linker on peripheral surface of SPIONs. The synthesis of HA-Glutamic Acid (GA)@SPIONs was included oxidization of nanoparticle's surface with H2O2 followed by activation of hydroxyl group and reacting glutamic acid as an intermediate molecule demonstrating transfection of lung cancer cells. Fourier transform infrared (FTIR) and zeta-potential studies confirmed the chemical bonding between amino acid linker and polysaccharides. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay showed that HA-SPIONs-treated cells remained 82.9% ± 2.7% alive at high particle dosage (200 µg/mL iron concentration), whereas GA-SPIONs and bare SPIONs (B-SPIONs) treated cells had only 59.3% ± 13.4% and 26.5% ± 3.1% survival rate at the same conditions, respectively. Confocal microscopy analysis showed increased cellular internalization of HA-SPIONs compared to non-interacting agarose coated SPIONs (AgA-SPIONs).

Paecilomycies japonica reduces repeated nicotine-induced neuronal and behavioral activation in rats.

BACKGROUND: Many studies have demonstrated that repeated injections of nicotine can produce progressive increases in locomotor activity and enhanced expression of c-fos and tyrosine hydroxylase (TH) in brain dopaminergic areas. Paecilomyces japonica (PJ) is a herbal medicine that is commonly used to treat opiate and other addictions in Eastern Asia. However, its influence on nicotine addiction has not been examined. This study was carried out to investigate the effects of PJ on repeated nicotine-induced behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. METHODS: Rats were pretreated with PJ (10, 25, 50, 100, and 200 mg/kg, intraperitoneally) 30 min before repeated injections of nicotine (0.4 mg/kg, subcutaneously, twice daily for 7 days). Locomotor activity was measured in rats during 7-day nicotine treatments. On the seventh day, c-Fos and TH expression were assessed. RESULTS: Pretreatment with PJ decreased the development of nicotine-induced sensitization, c-Fos expression in the nucleus accumbens and striatum, and TH expression in the ventral tegmental area. PJ decreased nicotine-induced locomotor activity by modulating brain dopaminergic systems. CONCLUSION: The results of the present study suggest that PJ may be a useful agent for preventing and treating nicotine addiction.

Development of the quantitative indicator of abdominal examination for clinical application: a pilot study.

OBJECTIVES: Abdominal examination (AE) is the evaluation of the status of illness by examining the abdominal region in traditional Korean medicine (TKM). Although AE is currently considered an important diagnostic method in TKM, owing to its clinical usage, no studies have been conducted to objectively assess its accuracy and develop standards. DESIGN: Twelve healthy subjects and 21 patients with functional dyspepsia have participated in this study. The patients were classified into epigastric discomfort group (n=11) and epigastric discomfort with tenderness group (n=10) according to the clinical diagnosis by AE. After evaluating the subjective epigastric discomfort in all subjects, two independent clinicians measured the pressure pain threshold (PPT) two times at an acupoint (CV 14) using an algometer. We then assessed the interrater and intrarater reliability of the PPT measurements and evaluated the validity (sensitivity and specificity) via a receiver operating characteristic plot and optimal cutoff value. RESULTS: The results of the interrater reliability test showed a very strong correlation (correlation coefficient range: 0.82-0.91). The results of intrarater reliability test also showed a higher than average correlation (intraclass correlation coefficient: 0.58-0.70). The optimal cutoff value of PPT in the epigastric area was 1.8 kg/cm(2) with 100% sensitivity and 54.54% specificity. CONCLUSIONS: PPT measurements in the epigastric area with an algometer demonstrated high reliability and validity for AE, which makes this approach potentially useful in clinical applications as a new quantitative measurement in TKM.

Meta-analysis of pain relief effects by laser irradiation on joint areas.

BACKGROUND: Laser therapy has been proposed as a physical therapy for musculoskeletal disorders and has attained popularity because no side effects have been reported after treatment. However, its true effectiveness is still controversial because several clinical trials have reported the ineffectiveness of lasers in treating pain. METHODS: In this systematic review, we investigate the clinical effectiveness of low-level laser therapy (LLLT) on joint pain. Clinical trials on joint pain satisfying the following conditions are included: the laser is irradiated on the joint area, the PEDro scale score is at least 5, and the effectiveness of the trial is measured using a visual analogue scale (VAS). To estimate the overall effectiveness of all included clinical trials, a mean weighted difference in change of pain on VAS was used. RESULTS: MEDLINE is the main source of the literature search. After the literature search, 22 trials related to joint pain were selected. The average methodological quality score of the 22 trials consisting of 1014 patients was 7.96 on the PEDro scale; 11 trials reported positive effects and 11 trials reported negative effects. The mean weighted difference in change of pain on VAS was 13.96 mm (95% CI, 7.24-20.69) in favor of the active LLLT groups. When we only considered the clinical trials in which the energy dose was within the dose range suggested in the review by Bjordal et al. in 2003 and in World Association for Laser Therapy (WALT) dose recommendation, the mean effect sizes were 19.88 and 21.05 mm in favor of the true LLLT groups, respectively. CONCLUSIONS: The review shows that laser therapy on the joint reduces pain in patients. Moreover, when we restrict the energy doses of the laser therapy into the dose window suggested in the previous study, we can expect more reliable pain relief treatments.

Inhibition of atopic dermatitis by topical application of silymarin in NC/Nga mice.

Silymarin has been known to inhibit chemical-induced irritant contact dermatitis. In the present study, we report that topical application of silymarin suppresses dust mite extract (DPE)-induced atopic dermatitis (AD) in NC/Nga mice. Repeated topical application of ears with DPE caused AD-like skin lesions in NC/Nga mice. However, silymarin reduced AD-like skin lesions in these mice, resulting in decreased ear swelling and leukocyte infiltration into the ear. Moreover, our results showed that mast cell infiltration into the ear was suppressed by silymarin treatment in DPE-treated NC/Nga mice. Silymarin also reduced plasma level of IL-4 and IgE in these mice. Further study demonstrated that the mRNA expression of IL-4 was increased and that of IFN-gamma was decreased by DPE treatment in the ears of NC/Nga mice. However, DPE-induced changes in IL-4 and IFN-gamma mRNA expression were reversed by silymarin. DPE-induced increase in TNF-alpha mRNA expression was also suppressed by silymarin treatment. The results presented in this report suggest that silymarin might be beneficial for the treatment of AD.

Antiinflammatory activity of methanol extract isolated from stem bark of Magnolia kobus.

The present study reports the antiinflammatory activity of a methanol extract isolated from the stem bark of Magnolia kobus (MK). MK potently inhibited lipopolysaccharide (LPS)-induced production of nitric oxide and interleukin-1beta (IL-1beta) in RAW 264.7 cells, a murine macrophage-like cell line. The secretion of tumor necrosis factor-alpha (TNF-alpha) was also suppressed in LPS-stimulated RAW 264.7 cells although the magnitude of inhibition was weaker than that of nitric oxide and IL-1beta. The mRNA expressions of inducible nitric oxide synthase (iNOS), IL-1beta and TNF-alpha were also suppressed by MK in LPS-stimulated RAW 264.7 cells. Further study demonstrated that LPS-induced DNA binding of AP-1 and phosphorylation of c-jun N-terminal kinase (JNK) were inhibited by MK treatment in RAW 264.7 cells, whereas phosphorylation of p38 mitogen-activated protein kinase was unaffected. Moreover, topical application of MK suppressed ear swelling in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation model. Collectively, these results suggest that MK exerts antiinflammatory effects in vitro and in vivo and this might be mediated, at least in part, by blocking AP-1 and JNK activation.

Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice.

Irritant contact dermatitis (ICD) is a non-allergic local inflammatory reaction of a skin and one of the most frequent occupational health problems. Silymarin has been clinically used in Europe for a long time to treat liver diseases and also known to have anti-cancer and anti-inflammatory activities. In the present study, we report that topical application of silymarin reduces chemical-induced ICD. Topical application of 2,4-dinitrochlorobenzene (DNCB) induced an ear swelling in BALB/c mice and silymarin suppressed DNCB-induced increase in ear thickness. Prophylactic and therapeutic application of silymarin showed similar effect on DNCB-induced increase in ear thickness and skin water content. In addition, phobor ester- or croton oil-induced increase in ear thickness was also inhibited by silymarin treatment. Silymarin also blocked neutrophil accumulation into the ear induced by these irritants. Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT. Silymarin also blocked TNF-alpha- and DNCB-induced NF-kappaB activation in HaCaT. Collectively, these results demonstrate that topically applied silymarin inhibits chemical-induced ICD in mice and this might be mediated, at least in part, by blocking NF-kappaB activation and consequently inhibiting the expression of cytokines and adhesion molecules.