Search

Cyanide is a highly toxic agent that has been frequently used for suicide in South Korea. It is also used in various industrial fields, such as metal plating, in which many accidental cyanide intoxications have occurred. To overcome the disadvantages of conventional cyanide analysis methods, a simple and fast method for the analysis of cyanide in whole blood using ion chromatography (IC) with amperometric detection was developed in this study. Whole blood samples were deproteinized, diluted, and analyzed using an IC-amperometric detection system. The limits of detection and quantitation were 0.1 and 0.2 mg/L, respectively. The method showed good linearity in the range of 0.2 to 50 mg/L with R2 > 0.99. The intra- and inter-assay precision and accuracy values were

Objectives: This study aimed to review the clinical research of the gut microbiome for respiratory diseases to assist the design of trials for respiratory diseases by regulating the gut microbiome with herbal medicine later. Methods: We searched three international databases (PubMed, CENTRAL and EMBASE) to investigate randomized controlled trials (RCTs) of the gut microbiome for respiratory diseases. The selected trials were analyzed by study design, subject diseases, inclusion/exclusion criteria, sample size, study period, intervention group, control group, outcome measures, and study results. Results: A total of 25 studies were included and published from 1994 to 2021 mostly in Europe and Asia. Subject diseases were many in the order of respiratory tract infection, cystic fibrosis, allergy, and so on. As outcome measures, the gut microbiome in a fecal sample was analyzed by 16S rRNA sequencing analysis method, and symptom assessment tools related each disease were used. Major intervention drugs were probiotics and the results were mostly improved in the composition and diversity of the gut microbiome. Conclusion: Clinical studies of the gut microbiome for respiratory diseases have confirmed various effects and this review provides basic data for a well-designed clinical study for respiratory diseases by regulating the gut microbiome with herbal medicine.

Objectives: This study is aimed to evaluate the protective effects of GGX on lung injury of Chronic Obstructive Lung Disease (COPD) mice model. Materials and Methods: C57BL/6 mice were challenged with lipopolysaccharide (LPS) and cigarette smoke extract (CSE) and then treated with vehicle only (Control group), dexamethasone 3 ㎎/㎏ (Dexa group), gam-gil-tang 200 ㎎/㎏ (GGT group), GGX 100, 200, and 400 ㎎/㎏ (GGX group). After sacrifice, its bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed with cytospin, Enzyme-Linked Immunosorbent Assay (ELISA), real-time polymerase chain reaction (PCR) and hematoxylin & eosin (H&E), and Masson’s trichrome staining. Results: In the COPD model, GGX significantly inhibited the increase of neutrophils, TNF-α, IL-17A, CXCL-1, MIP2 in BALF and TNF-α, IL-1β, IL-10 mRNA expression in lung tissue. It also decreased the severity of histological lung injury. Conclusion: This study suggests the usability of GGX for COPD patients by controlling lung tissue injury.

Testosterone and free testosterone levels decrease in men as they age, consequently inducing andropause symptoms, such as weight gain, fatigue, and depression. Therefore, this study aimed to evaluate the reducing effect of New Zealand spinach (NZS) on these androgenic symptoms by orally administering its extract to 26-week-old rats for four weeks. Biochemical blood testing was conducted, and the andropause symptoms-related indicators and muscular endurance levels were examined. In the NZS extract-treated rats, the decrease in muscle mass was suppressed, and immobility time was reduced in the forced swim test. In addition, the grip force and muscular endurance of the forelimbs were significantly increased compared to the control group; therefore, NZS extract exhibits a positive effect on the maintenance of muscle mass and improves muscular endurance. The representative male hormones, testosterone and progesterone, in the NZS extract-treated group were 1.84 times and 2.48 times higher than those in the control groups, respectively. Moreover, cholesterol and low-density lipoprotein, which affect lipid metabolism, were significantly reduced in the NZS extract-treated group. Overall, NZS extract shows potential for further development as a functional food material for improving muscle strength and relieving andropause symptoms.

Metomidate and etomidate belong to the non-barbiturate imidazole family of sedative-hypnotics and elicit little analgesic action when used alone. Metomidate, in particular, has little analgesic activity in humans and is, therefore, used for veterinary purposes. In 2019, a Korean woman in her twenties was found unconscious in a motel bath and eventually died. Etomidate, alprazolam, escitalopram, and metomidate were detected in the postmortem specimens. To our knowledge, this is the first case of human metomidate abuse reported in the Republic of Korea. In this research, a simple and reliable method was developed for the analysis of metomidate and etomidate in human blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Blood samples were deproteinized with acetonitrile, filtered, and analyzed by LC-MS/MS. Linear calibration curves were obtained with six concentrations ranging from 1 to 50 ng/ml for metomidate and 10 to 500 ng/ml for etomidate. The method was validated by assessing the selectivity, linearity, limit of detection (LOD), limit of quantitation (LOQ), intra- and inter-day precision and accuracy, matrix effect, and stability and successfully applied to the analysis of metomidate and etomidate in human blood samples. In a postmortem case, the concentrations of metomidate and etomidate were found to be 8 and 110 ng/ml in femoral blood and 6 and 210 ng/ml in cardiac blood, respectively.

Peanut allergy is a major cause of food-induced anaphylaxis and subsequent fatality. Food allergies are becoming an increasingly important global health issue. This study was undertaken to verify the effects of peanut sprout extract (PNSE) on the inhibition of allergic and anaphylactic responses using a peanut (PN)-immunized food allergy mouse model. Fresh peanut sprouts were germinated for 0, 3, 5, and 7 days using mature peanuts. Mice were then sensitized to cholera toxin plus PNE or PNSE by intragastric administration on days 0 and 7, and were then challenged with PNE or PNSE on days 21 and 35. After 5 weeks, we examined the mucosal mast cell degranulation, ear swelling, and systemic anaphylaxis stimulated by PNE extract, in comparison with PNSE. Subsequently, Ara h1, a biomarker of PNE allergy; serum levels; and Th1/Th2 cytokine production in supernatants of cultured splenocytes were measured. PNSE treatment significantly attenuated the secretion of anti-Ara h1 antibody, mucosal mast cell degranulation, degree of systemic anaphylaxis, and ear swelling and increased the production of IFN-γ and IL-10, with a decrease in IL-4 secretion. The results of this study show that the allergenicity of PNE could be reduced by germination, which caused downregulation of Th2 lymphocyte activity, systemic anaphylactic response, and mast cell-mediated ear swelling in PNE-sensitized mice.

Selegiline (SE) is a selective, irreversible monoamine oxidase-B inhibitor, used for reducing symptoms in early-stage Parkinson’s disease. The metabolites of SE include l-methamphetamine, l-amphetamine and desmethylselegiline (DSE). The stereoisomers of SE metabolites, d-methamphetamine and d-amphetamine are highly addictive psychostimulants and some of the most abused drugs in South Korea. In order to differentiate medical SE users form illicit methamphetamine abusers, it is important to distinguish between the l-isomers and d-isomers in urine samples. A 52-year-old male, seemingly under the influence of intoxication and demonstrating abnormal behavior, was reported to the police. The initial urine test using a methamphetamine detection kit demonstrated a positive result. Given the initial results, the police officer requested a further analysis of the urine sample. The urine sample was screened using headspace-solid phase microextraction-gas chromatography–mass spectrometry (HS-SPME-GC–MS). Both methamphetamine and amphetamine were detected, in addition to SE and DSE. To quantitate methamphetamine and amphetamine by HS-SPME-GC–MS, we performed a standard addition method due to the matrix effect of the case sample. Consistent with previous studies, our results indicated that the ratio of amphetamine to methamphetamine was 0.27, which was in the range of SE ingestion. Furthermore, we confirmed l-methamphetamine and l-amphetamine by chiral derivatization using (R)-(−)-α-methoxy-α-(trifluoromethyl) phenylacetyl chloride.

Veronica persica is a flowering plant belonging to the family Scrophulariaceae. Here, we aimed to evaluate the pharmacological activity of the ethanol extract of Veronica persica (EEVP) in an airway inflammation model. We examined airway responsiveness to aerosolized methacholine, serum immunoglobulin (Ig)E levels, and total cell numbers in the lung and bronchoalveolar lavage fluid (BALF). Histological analysis of the lung tissue was performed using hematoxylin-eosin, Masson trichrome, or periodic acid-Schiff staining. Fluorescence-activated cell sorting analysis in the lung and BALF was applied to clarify the changes in immune cell types. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were applied to investigate cytokine levels and gene expression related to airway inflammation. STAT-3/6 phosphorylation was examined in primary bronchial/tracheal epithelial cells using western blot analysis. EEVP significantly suppressed total IgE levels and methacholine-induced increase of Penh value in the HDM-challenged mouse model. EEVP also attenuated the severity of airway remodeling in lung tissues and decreased eosinophil and neutrophil infiltration in the lungs and BALF. EEVP significantly reduced the production of cytokines in BAL and splenocyte culture medium, and the expression of mRNAs related to airway inflammation in the lung tissue. EEVP suppressed IL-4/13-induced STAT-3/6 phosphorylation in the epithelial cells. We showed for the first time that EEVP effectively inhibits eosinophilic airway inflammation by suppressing the expression of inflammatory factors for T cell activation and polarization, and inhibits MCP-1 production of bronchial/tracheal epithelial cells by suppressing STAT-3/6 activation. EEVP may be a potential pharmacological agent to prevent inflammatory airway diseases.

Background. Allergic rhinitis (AR) is a common disease, and conventional medications are often insufficient for treatment. Bojungikgi-tang (BJIGT) is an herbal medicine widely used in traditional medicine and has anti-inflammatory and immunoregulatory effects. We hypothesize that BJIGT would improve nasal symptoms in patients with persistent AR (PAR). Methods. This is a randomized, double-blind, placebo-controlled, phase II trial. A total of 105 patients, identified with perennial allergens, with a history of PAR and a mean total nasal symptom score (TNSS) ≥ 5 during the run-in period will be recruited from Daejeon Korean Medicine Hospital. Participants will be randomly assigned to a high-dose BJIGT group, standard-dose BJIGT group, or control group (placebo) in a 1 : 1 : 1 allocation ratio after a week run-in period. The treatment medication will be taken three times per day for 4 weeks. The primary outcome measure is the mean change in the TNSS before and after medication. The secondary outcome measures include the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, total IgE and eosinophil count, overall assessment of AR, pattern identification questionnaire for AR, and Sasang constitution. Discussion. The aim of this study is to investigate the efficacy and safety of BJIGT in the treatment of PAR and to determine the suitable dosage of BJIGT. Therefore, we planned a randomized, controlled, phase II trial of two different doses of BJIGT compared with placebo, and the results of this study are expected to provide evidence for the use of BJIGT as a treatment of PAR. Trial Registration. The National Clinical Trial Registry Clinical Research Information Service, CRIS, KCT0006616, https://cris.nih.go.kr/cris/search/detailSearch.do/20706.

Background. Obstructive airway disease is a major health problem and has a great impact on global socioeconomic burden. Despite therapeutic advances in recent decades, there is still a need for effective and safe therapeutic agents for patients with asthma or chronic obstructive pulmonary disease (COPD). Methods. This prospective observational study explored the effects of herbal medicines in patients with asthma and COPD. All participants visited the hospital at least every 4 weeks for 12 weeks to receive their herbal medicines based on their pattern identification and to evaluate safety and efficacy endpoints. We followed the diagnostic criteria used by Korean medicine doctors to prescribe herbal medicines, explored variations in prescribed herbal medicines, and explored a number of clinical features in patients with asthma or COPD. Results. A total of 24 patients were enrolled: 14 were diagnosed with asthma and 10 with COPD and 19 completed the study. After 12 weeks of herbal medicine treatment, herbal medicines significantly improved the modified Clinical Asthma Measurement Scale in Oriental Medicine-V in asthma patients and the modified Medical Research Council Dyspnoea Scale and St. George’s Respiratory Questionnaire in COPD patients. For all patients, modified Medical Research Council Dyspnoea Scale score and interleukin-13 were found to be significantly different after treatment. Additionally, the majority of patients were satisfied with our herbal medicine treatments, and no severe adverse events were reported during the study. Conclusions. Our study provides preliminary clinical data on the safety and efficacy of herbal medicines in patients with asthma and COPD.

We studied the activities of Siraitia grosvenorii extracts (SGE) on airway inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) stimulated by cigarette smoke extract (CSE) and lipopolysaccharide (LPS), as well as in LPS-treated human bronchial epithelial cell line (BEAS-2B). SGE improved the viability of LPS-incubated BEAS-2B cells and inhibited the expression and production of inflammatory cytokines. SGE also attenuated the mitogen-activated protein kinase (MAPK)-nuclear factor-kappa B (NF-κB) signaling activated by LPS stimulation in BEAS-2B cells. In mice stimulated by CSE and LPS, we observed the infiltration of immune cells into the airway after COPD induction. SGE reduced the number of activated T cells, B cells, and neutrophils in bronchoalveolar fluid (BALF), lung tissue, mesenteric lymph node, and peripheral blood mononuclear cells, as well as inhibited infiltration into organs and mucus production. The secretion of cytokines in BALF and the expression level of pro-inflammatory cytokines, mucin 5AC, Transient receptor potential vanilloid 1, and Transient receptor potential ankyrin 1 in lung tissue were alleviated by SGE. In addition, to investigate the activity of SGE on expectoration, we evaluated phenol red secretions in the trachea of mice. SGE administration showed the effect of improving expectoration through an increase in phenol red secretion. Consequently, SGE attenuates the airway inflammatory response in CSE/LPS-stimulated COPD. These findings indicate that SGE may be a potential herbal candidate for the therapy of COPD.

Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. Pulsed electromagnetic field (PEMF) stimulation induces cell proliferation of articular chondrocytes. We developed a method for growth promotion using equipment with PEMF. In this study, we aimed to evaluate the effects of PEMF on the growth rate of growth plates using an animal model. An experimental study was conducted on 16 3-week-old rats to validate the effects of the growth care device on growth and development by PEMF stimulation at 28 Hz and 20 Gauss. The tibia bones of the groups with and without PEMF administration were dissected after 10 days, and then, the length of the growth plate of the knee and levels of insulin-like growth factor (IGF)-1 hormone in serum were measured. The length of the growth plate on the tibia bone and the levels of circulating IGF-1 were significantly increased by 25.6% and 13.6%, respectively, in the experimental group to which PEMF was applied compared to those of the control group, without any side effects. These results suggest that PEMF can safely stimulate growth of the growth plate in a non-invasive manner to promote bone growth.

Benign prostatic hyperplasia (BPH) is the most common symptomatic abnormality of the human prostate characterized by uncontrolled proliferation of the prostate gland. In this study, we investigated the effect of bamboo, Phyllostachys pubescens, leaves extract (PPE) on human 5α-reductase type 2 (SRD5A2) gene promoter activity in human prostate cell lines and the protective effect of PPE on a testosterone-induced BPH rat model. PPE repressed human SRD5A2 promoter activity and its mRNA expression. The rats treated with PPE for 4 weeks showed a significantly attenuated prostate weight compared to vehicle control. PPE-treated rats also showed reduced serum dihydrotestosterone, testosterone, prostate-specific antigen, and SRD5A2 levels by testosterone injection. Quantitative real-time polymerase chain reaction showed that PPE treatment significantly decreased mRNA expression of SRD5A2, androgen receptor (AR), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor 2 compared with the vehicle-treated, testosterone-injected rats in the prostate. Furthermore, PPE treatment showed reduced AR, PCNA, and tumor necrosis factor alpha expression in the prostate via immunohistofluorescence staining. In conclusion, oral administration of PPE prevented and inhibited the development and progression of enlarged prostate lesions in testosterone-induced animal models through various anti-proliferative and anti-inflammatory pharmacological effects and induced suppression of SRD5A2 gene expression.

Benign prostatic hyperplasia (BPH) is the most common symptomatic abnormality of the human prostate characterized by uncontrolled proliferation of the prostate gland. In this study, we investigated the effect of bamboo, Phyllostachys pubescens, leaves extract (PPE) on human 5α-reductase type 2 (SRD5A2) gene promoter activity in human prostate cell lines and the protective effect of PPE on a testosterone-induced BPH rat model. PPE repressed human SRD5A2 promoter activity and its mRNA expression. The rats treated with PPE for 4 weeks showed a significantly attenuated prostate weight compared to vehicle control. PPE-treated rats also showed reduced serum dihydrotestosterone, testosterone, prostate-specific antigen, and SRD5A2 levels by testosterone injection. Quantitative real-time polymerase chain reaction showed that PPE treatment significantly decreased mRNA expression of SRD5A2, androgen receptor (AR), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor 2 compared with the vehicle-treated, testosterone-injected rats in the prostate. Furthermore, PPE treatment showed reduced AR, PCNA, and tumor necrosis factor alpha expression in the prostate via immunohistofluorescence staining. In conclusion, oral administration of PPE prevented and inhibited the development and progression of enlarged prostate lesions in testosterone-induced animal models through various anti-proliferative and anti-inflammatory pharmacological effects and induced suppression of SRD5A2 gene expression.

The aim of this study was to evaluate the efficacy and safety of CAEC (Canavalia gladiata arctium lappa extract complex) in adults with white blood cells between 3 and 8 × 103 cells/µL by assessing natural killer (NK) cell activity and immune-related biomarkers. Overall, 100 participants (CAEC group = 50, placebo group = 50) were randomised, and administered CAEC or placebo once daily for 8 weeks, with an evaluation visit performed every 4 weeks. NK cell activity, the primary outcome, significantly increased in CAEC when compared with the placebo at effector-to-target (E:T) ratios of 25:1 and 50:1 after 8 weeks. Compared with the placebo group, IL-10 demonstrated significant differences at week 8 in the CAEC group. Our findings demonstrate that CAEC is safe and enhances immune function by stimulating NK cell activity through IL-10 expression. Hence, we anticipate that CAEC can be developed as a functional food for stimulating immunity.

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-&gamma, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-&alpha, /IFN-&gamma, induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.

The consequences of increased industrialization increased the risk of asthma and breathing difficulties due to increased particulate matter in the air. We aim to investigate the therapeutic properties of Hypericum ascyron L. extract (HAE) in airway inflammation and unravel its mechanism of action. We conducted nitric oxide and cell viability assay, real-time PCR and western blot analyses along with in vitro studies. in vivo studies include a model of coal fly ash and diesel exhaust particle (CFD)-induced airway inflammation in mice. HAE reduced coal fly ash (CFA)-induced nitric oxide secretion without exhibiting cytotoxicity in MH-S cells. HAE also reduced the mRNA expression of pro-inflammatory cytokines and reduced the expression of proteins in the NFκB and MAPK pathways. In a mice model of CFD-induced airway inflammation, HAE effectively reduced neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and increased the amount of T cells in the BALF, lungs, and blood while reducing all other immune cell subtypes to reduce airway inflammatory response. CXCL-1, IL-17, MIP-2, and TNF-α expression in the BALF were also reduced. HAE effectively reduced MIP-2 and TNF-α mRNA expression in the lung tissue of mice. In a nutshell, HAE is effective in preventing airway inflammation induced by CFA in MH-S cells, as well as inflammation induced by CFD in mice.

Background Atopic dermatitis is a chronic inflammatory skin disease in humans. Although Olea europaea leaf extract (OLE) and Spirodela polyrhiza extract (SPE) have been used to protect against skin damage, the effects of their combined administration on atopic dermatitis have yet to studied. Purpose In this study, we evaluated the potential therapeutic effects of an OLE and SPE combination on the progression of atopic dermatitis and the possible mechanisms underlying these effects in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. Methods Atopic dermatitis was induced by topical application of 0.2% w/v DNCB prepared in an olive oil:acetone solution (1:3), and thereafter OLE, SPE and OLE + SPE were administered orally for 5 weeks. We determined atopic dermatitis symptoms, serum IgE levels, and levels of cytokine- and gene expression in the dorsal skin and splenocytes, and performed histological and immune cell subtype analyses. The expression of skin barrier-related proteins (filaggrin, sirtuin 1, and claudin 1) was also evaluated. Results The OLE + SPE combination significantly ameliorated atopic dermatitis symptoms, including dermatitis scores, and reduced epidermal thickness and infiltration of different inflammatory cells in mice with DNCB-induced atopic dermatitis. It also significantly reduced the number of CD4+, CD8+, and CD4+/CD69+ T cells; immunoglobulin E-producing B cells (CD23+/B220+) in the axillary lymph nodes; CD3+ T-cell eosinophils (chemokine–chemokine receptor 3+/CD11b+) in the skin; and CD3+ T cells, immunoglobulin E-producing B cells (CD23+/B220+), and eosinophils in peripheral blood mononuclear cells. Additionally, the experimental combination lowered levels of serum immunoglobulin E and histamine, as well as Th2-mediated cytokines, and interleukin-4, -5, and -13, whereas it increased the levels of Th1-mediated cytokine interferon-γ in splenocytes. Furthermore, the preparation significantly restored expression of the skin barrier-related proteins filaggrin, sirtuin 1, and claudin 1, and also reduced the expression of the inflammatory cytokine interleukin-6 and chemokine–chemokine receptor 3, as well as the pruritus-related cytokine interleukin-31 and interleukin-31 receptor, in atopic dermatitis skin lesions. Conclusion Taken together, our findings indicate that administration of a combination of OLE and SPE can alleviate atopic dermatitis symptoms by regulating immune balance and skin barrier function and may be an effective therapeutic option for the treatment of atopic dermatitis.

Methylphenidate (MPH) is one of the most commonly prescribed stimulants for attention deficit hyperactivity disorder and its abuse is on the rise with its growing availability. Some analytical methods have been reported for the detection of MPH in hair. However, the concentration range of MPH as well as its metabolite, ritalinic acid (RA) in the hair of MPH abuse cases has not been reported. In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of MPH and RA in hair. Sample preparation was carried out by a simple methanol extraction using 10mg of hair. Limits of detection for MPH and RA in hair were 0.5pg/mg and 1pg/mg, respectively, and the limits of quantification (LOQs) were 1pg/mg for both the analytes. Validation results showed good linearity in the range of 1-100pg/mg with acceptable precision and accuracy. The developed method was applied to real hair samples obtained from ten drug users who obtained MPH illegally without a prescription. MPH concentrations in the hair samples ranged from 1.0pg/mg to 265.0pg/mg, and RA was present at concentrationsLOQ-76.3pg/mg. In this study, hair analysis and background findings revealed that most subjects have abused illicit substances (methamphetamine, Δ

Industrial development, along with the rapid growth of the economy, has greatly improved the quality of life in humans. Moreover, advancements in medical technology have increased life expectancy. Small particles increase airway inflammation when they penetrate the alveoli. We observed that GHX02 decreased the frequency and delayed the onset time of citric acid-induced coughing in guinea pigs. A phenol red secretion assay indicated that the GHX02 extract exhibits potent expectorant activity. The GHX02 extract also greatly reduced leukocyte levels. Our results indicate that GHX02 inhibits airway inflammation, reduces sputum production, and relieves cough. The GHX02 extract suppressed histamine release from mast cells resulting from compound 48/80-induced degranulation. The extract exhibited antimicrobial activity against Streptococcus pneumoniae and significantly inhibited the formation of LTC4. At high concentrations, the GHX02 extract suppressed the formation of PGE2 (prostaglandin E2). Interleukin (IL)-4 and IL-13 levels decreased with an increasing dosage of GHX02. Oral administration of the GHX02 extract suppressed PM10D-induced inflammatory symptoms in the lung, including increased alveolar wall thickness, accumulation of collagen fibers, and cytokine release. Treatment with the GHX02 extract also resulted in lower levels of inflammatory cells, in bronchoalveolar lavage fluid and lung tissue. Our results indicate that GHX02 may be a useful therapeutic agent for treatment of respiratory diseases.

Chronic obstructive pulmonary disease (COPD) is caused by exposure to toxic particles, such as coal fly ash (CFA), diesel-exhaust particle (DEP), and cigarette smoke (CS), leading to chronic bronchitis, mucus production, and a subsequent lung dysfunction. This study, using a mouse model of COPD, aimed to evaluate the effect of herbal combinational medication of Glycyrrhiza glabra (GG), Agastache rugosa (AR) containing glycyrrhizic acid (GA), and tilianin (TN) as active ingredients. GA, a major active component of GG, possesses a range of pharmacological and biological activities including anti-inflammatory, anti-allergic, anti-oxidative. TN is a major flavonoid that is present in AR. It has been reported to have anti-inflammatory effects of potential utility as an anti-COPD agent. The COPD in the mice model was induced by a challenge with CFA and DEP. BALB/c mice received CFA and DEP alternately three times for 2 weeks to induce COPD. The herbal mixture of GG, AR, and TN significantly decreased the number of neutrophils in the lungs and bronchoalveolar lavage (BAL) fluid. It also significantly reduced the production of C-X-C motif chemokine ligand 2 (CXCL-2), IL-17A, CXCL-1, TNF-&alpha, symmetric dimethylarginine (SDMA) in BALF and CXCL-2, IL-17A, CXCL-1, MUC5AC, transient receptor potential vanilloid-1 (TRPV1), IL-6, COX-2, NOS-II, and TNF-&alpha, mRNA expression in the lung tissue. Notably, a combination of GG and AR was more effective at regulating such therapeutic targets than GG or AR alone. The histolopathological lung injury was alleviated by treatment with the herbal mixture and their active ingredients (especially TN). In this study, the herbal combinational mixture more effectively inhibited neutrophilic airway inflammation by regulating the expression of inflammatory cytokines and CXCL-2 by blocking the IL-17/STAT3 pathway. Therefore, a herbal mixture of GG and AR may be a potential therapeutic agent to treat COPD.

In Korea, an increasing number of people attempt to evade military conscription by posing as mental health patients. To verify the authenticity of mental illness, there is a need to detect wide range of psychoactive agents in biological specimens of conscription candidates. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous determination of 18 psychoactive agents and 6 metabolites in human plasma. The method was characterized by the use of a simple, fast and cheap protein precipitation as sample preparation, a rapid run time (11 min) and a low volume of plasma sample (200 μL). The analytes were monitored under the scheduled multiple reaction monitoring (sMRM) positive and negative mode using electrospray ionization (ESI). The essential validation parameters including selectivity, linearity, accuracy, precision, matrix effect and recovery were satisfactory. The limit of detection ranged from 0.0005 to 0.001 μg/mL, and limit of quantitation ranged from 0.005 to 0.025 μg/mL. The developed method was successfully applied to 323 actual plasma samples submitted by Korea central physical examination center of military manpower administration in 2016, and is expected to contribute to the rapid and accurate disposition of military service.

Canavalia gladiata (C. gladiata) and Arctium lappa (A. lappa), used in traditional medicine and food. However, their preventive effects in dextran sulphate sodium (DSS)-induced inflammatory bowel disease (IBD) remain unclear. We found that the C. gladiata and A. lappa mixture suppressed inflammation in LPS-induced RAW 264.7 cells. The mixture increased the population and activation of immune cells, up-regulation of cell cycle, and induction of IgA and IgG production in wild-type mice. Furthermore, the extract mixture prevented clinical IBD symptoms and restored IgA production in IBD mice. Similarly, a mixture of the marker compounds, chicoric acid and lupeol, ameliorated IBD-associated clinical signs, improved the population and activation of immune cells and functional defects in natural killer (NK) cells and reduced production of IgA in these mice. In conclusion, the C. gladiata and A. lappa mixture ameliorated progression of DSS-induced IBD by enhancing immune responses and recovering functional immune cell defects.

Ethnopharmacological relevance The modified gamgil-tang (GGX) is a mixture of four herbal medicine including Platycodi Radix, Glycyrrhizae Radix, Lonicerae Flos and Mori Radicis Cortex which has been traditionally used to treat lung and airway diseases to relieve symptoms like sore throat, cough, and sputum in Korea. Its major component chlorogenic acid had been reported to have antioxidant, antibacterial, hepatoprotective, cardioprotective, anti-inflammatory, antiviral, and anti-microbial activity. Aim of the study To identify the inhibitory effect of GGX in a particulate matter (PM) induced lung injury mouse model. Materials and methods We evaluated NO production, the release of TNF-α and IFN-γ in PM-induced MH-S cells, and the number of neutrophils, immune cell subtypes, and the secretion of TNF-α, IL-17, CXCL-1, MIP-2 in the PM-stimulated mouse model to assess the inhibitory effect of GGX against PM. In addition, as exposure to PM increases respiratory symptoms, typically cough and sputum, we attempted to evaluate the antitussive and expectorant activities of GGX. Results Our study provided evidence that GGX has inhibitory effects in PM-induced lung injury by inhibiting the increase in neutrophil and inflammatory mediators, deactivating T cells, and ameliorating lung tissue damage. Notably, GGX reduced PM-induced neutrophilic inflammation by attenuating the number of neutrophils and regulating the secretion of neutrophil-related cytokines and chemokines, such as TNF-α, IL-17, MIP2, and CXCL-1. In addition, GGX demonstrated an antitussive activity by significantly reducing citric acid-induced cough frequency and delaying the latent period and expectorant activities by the increased phenol red secretion compared to the control group. Conclusions GGX is expected to be an effective herbal remedy to prevent PM-induced respiratory disease.

Regulatory T cells play an important role in autoimmunity and have been shown to exert anti-inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin-induced CD4+CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR). Luteolin significantly inhibited OVA-induced increase in immune cell and eosinophil counts as well as IL-4, IL-5, IL-13, and eotaxin levels in bronchoalveolar lavage fluid (BAL Fluid). Luteolin and cyclosporine A (CsA) which was a positive control also substantially reduced OVA-specific IgE levels, eotaxin 2 levels, and CCR3 expression in BAL Fluid. In contrast, luteolin significantly increased IL-10 and IFN-γ protein levels, as well as IL-10 and TGF-β1 mRNA expression in the lung. In vitro studies showed that the number of luteolin-induced CD4+CD25+ Treg (iTreg) cells was higher, with elevated levels of TGF-β1 and foxp3 mRNA expression in lungs tissue. Transfer of iTreg cells into OVA-sensitized mice reduced AHR, eosinophil recruitment, eotaxin, IgE, and Th2 cytokine expressions, and increased IFN-γ production in BAL Fluid after allergen challenge. Furthermore, adoptive transfer of iTreg cells prevented disease in a CD25-depleted mouse asthma model. Luteolin via induction of foxp3 and CD4+CD25+ Treg cells may represent a new strategy in the development of therapies for managing asthma.

Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans. In this study, we evaluated the effects of a mixture (NCM 1921) of omega-3 butter, omega-3 beef tallow oil, omega-3 lard oil, caprylic acid, lauric acid, choline, and Fe on AD in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. NCM 1921 significantly ameliorated the macroscopic and microscopic signs and reduced skin thickness and mast cell incorporation in the skin lesions of mice with DNCB-induced AD. Furthermore, it reduced serum immunoglobulin E levels, reduced the number of IgE-producing B cells, peripheral blood mononuclear cells, white blood cells, and differential white blood cells, and increased the number of lymphocytes. NCM 1921 normalized the total cell number in dorsal skin tissue, the axillary lymph node, and spleen following DNCB exposure and reduced the number of CD23+/B220+ cells in the axillary lymph node and CD3+ cells in dorsal skin tissue. Moreover, it reduced the levels of interleukin (IL)-4 and IL-13 but increased the levels of interferon-&gamma, in anti-CD3&ndash, stimulated splenocytes. Immunohistofluorescence staining showed that NCM 1921 treatment significantly increased claudin1, filaggrin, and Sirt1 protein expressions in AD skin lesions. These results suggest that NCM 1921 could be a valuable remedy for the treatment of AD.

Objectives: Allergic asthma generally presents with symptoms of wheezing, coughing, breathlessness, and airway inflammation. Seonpyejeongcheon-tang (SJT) consists of 12 herbs. It originated from Jeong-cheon-tang (JT), also known as Ding-chuan-tang, composed of 7 herbs, in She-sheng-zhong-miao-fang. This study aimed to evaluate the effects of local delivery of SJT via inhalable microparticles in an asthma mouse model. Methods: Microparticles containing SJT were produced by spray-drying with leucine as an excipient. SJT microparticles were evaluated with respect to their aerodynamic properties, in vitro cytotoxicity, in vivo toxicity, and therapeutic effects on ovalbumin (OVA)-induced asthma in comparison with orally-administered SJT. Results: SJT microparticles provided desirable aerodynamic properties (fine particle fraction of 48.9% +/- 6.4% and mass median aerodynamic diameter of 3.7 +/- 0.3 mu m). SJT microparticles did not show any cytotoxicity against RAW 264.7 macrophages at concentrations of 0.01 - 3 mg/mL. Inhaled SJT microparticles decreased the levels of IL-4, IL-5, IL-13, IL-17A, eotaxin and OVAIgE in bronchoalveolar lavage fluid (BALF) in mice with OVA-induced asthma. These effects were verified by histological evaluation of the levels of infiltration of inflammatory cells and collagen, destructions of alveoli and bronchioles, and hyperplasia of goblet cells in lung tissues. The effects of SJT microparticles in the asthma model were equivalent to those of orally-administered SJT extract. Conclusion: This study suggests that SJT is a promising agent for inhalation therapy for patients with asthma.

In Phytolaccaceae family, Phytolacca americana L. (American pokeweed) and P. esculenta Van Houtte (Chinese pokeweed) are the two representative species among the genus. Pokeweeds have triterpenoid saponins as toxic compounds in every part of the plant. The saponins phytolaccoside A, B, D, E, and G were isolated from P. americana, and esculentoside H, J, L, K, M, I, and N were isolated from P. esculenta. Along with saponins, their aglycones (phytolaccagenin, phytolaccagenic acid, esculentic acid and jaligonic acid) were also isolated from P. americana and P. esculenta. Two people who unknowingly ate misidentified pokeweed plant roots were transferred to the emergency room. Urine and gastric content after irrigation were collected from the first patient (patient 1), and blood and urine were collected from the second patient (patient 2). The samples were analyzed to identify toxic substances with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the blood sample, 1.9 ng/mL of esculentoside A and 1.5 ng/mL of esculentoside C were detected, while the concentration of esculentoside B and H were below the LLOQ. In gastric contents and ingested roots, esculentoside A, B, C, and H were identified. Esculentoside A, C, and H were identified in the urine of patient 1, and esculentoside A and C were identified in the urine sample of patient 2. The developed analytical method was validated for parameters such as linearity, limit of detection, precision, accuracy, matrix effect, recovery, and process efficiency, and they showed clear and unbiased results.

Background: Chronic obstructive pulmonary disease (COPD) is an irreversible disease characterized by cough, sputum production, and dyspnea, and has a high prevalence and mortality. Pulmonary rehabilitation (PR) is a management that improves the quality of life for COPD patients; however, PR is not readily accessible. Therefore, we developed lung-conduction exercises (LCE) that can be performed without any limitations. LCE consists of breathing, stretching, and tapping to relieve dyspnea in COPD patients. Methods/design: This randomized, assessor-blind, multicenter trial aims to recruit 54 patients with moderate and severe COPD. Subjects will be randomly allocated to a control group (only medication), an LCE group (medication + LCE, 5 times a week), or a PR group (medication + PR, 5 times a week). The 6-minute walk distance, pulmonary function tests (forced expiratory volume at 1 second, forced vital capacity, and forced expiratory volume at 1 second/forced vital capacity), modified Borg scale, modified medical research council dyspnea scale, COPD assessment test, and St. George respiratory questionnaire will be measured before starting the trial and after the 4th and 8th weeks to determine motor performance, lung function, and dyspnea. Conclusion: We aim to demonstrate that LCE is effective in improving symptoms and psychosomatic stability in COPD patients. Therefore, this trial will play an important role in fortifying the foundation of clinical application.

Chronic obstructive pulmonary disease (COPD), including pulmonary emphysema and chronic bronchitis as well as structural and inflammatory changes in small airways, is insensitive to corticosteroid therapies. This study aimed to evaluate the effects of Scutellaria baicalensis root extract (SB_E) in a mouse model of COPD. The COPD mouse model was produced by challenging C57BL/6 mice with a cigarette smoke extract and lipopolysaccharide (LPS). SB_E significantly decreased the neutrophil counts in blood and bronchoalveolar lavage fluid (BALF), and the production of tumor necrosis factor (TNF)-α, interleukin (IL)-17A, macrophage inflammatory protein 2 (MIP2), and chemokine (C-X-C motif) ligand 1 (CXCL-1) in BALF, and TNF-α mRNA expression in lung tissue. The histological lung injury was also alleviated by treatment with SB_E. Thus, SB_E effectively inhibited airway inflammation by regulating the expression of inflammatory cytokines by blocking MIP2 and CXCL-1 secretion. Therefore, S. baicalensis may be a potential therapeutic agent for COPD.

The effects of daucosterol have been identified in cancer therapy and neuronal diseases. However, the regulatory function of daucosterol in DSS-induced colitis has not yet been investigated. In this study, we evaluated the immunological and therapeutic effects of daucosterol in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Unlike vehicle mice, mice pre- or post-treated with daucosterol showed inhibition of body weight loss and the decrease in the disease activity index (DAI). In addition, daucosterol treatment rescued the DSS-induced decrease in colon length and disruption of the epithelial lining. Furthermore, it reduced DSS-induced production of reactive oxygen species (ROS), infiltration of macrophages, and expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Mice with colitis showed a decreased population of Foxp3+ cells, which was upregulated by daucosterol treatment. Furthermore, daucosterol increased natural killer (NK) cell activity and inhibited excessive IgA levels in mice with DSS-induced colitis. Collectively, our findings demonstrated that daucosterol significantly alleviated DSS-induced colitis, indicating the possibility of daucosterol as a therapeutic option for colitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Bleomycin (BLM) contributes to the induction of pulmonary inflammation and fibrosis in animals. Although skin and lung tissue inflammation is closely related in the pathogenesis of allergic diseases, a proper animal model for investigating the relationship between skin and lung inflammation is lacking. Therefore, we developed a mouse model of AD with relapsing dermatitis and pulmonary fibrosis caused by the administration of allergen and BLM. The present study determined whether lung injury caused by the bronchial application of BLM would exacerbate AD-like allergic inflammation induced by 2, 4-dinitrochlorobenzene (DNCB) in NC/Nga mice. NC/Nga mice treated with BLM and DNCB had increased severity of clinical symptoms and airway hyperresponsiveness as well as increased inflammatory cell infiltration and collagen deposition in the dorsal skin and lung. Compared to normal mice, interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in bronchoalveolar lavage fluid were increased in NC/Nga mice treated with both DNCB and BLM and in animals treated with DNCB alone. Administration of BLM and DNCB increased the levels of IL-4 and IL-13 production in spleen cells and eotaxin-2 mRNA expression in dorsal skin, compared to NC/Nga mice treated with DNCB alone. The total cell numbers in axillary lymph node, bronchoalveolar lavage, and thymus were increased in DNCB-BLM mice compared to those in mice treated with DNCB alone. Administration of BLM and DNCB increased the numbers of cluster of differentiation 4 (CD4)+ T cells and CD11b+granulocyte-differentiation antigen-1 (Gr-1)+ cells among peripheral blood mononuclear cells, CD4+ cells in bronchoalveolar lavage, CD4+ and B220+CD23+ B cells in the axillary lymph node, and CD4+ cells in thymus, compared to DNCB-treated mice. The number of total, CD4+, and CD11b+Gr-1+ cells in the lung were increased in both DNCB and DNCB-BLM mice. These results demonstrate that BLM aggravates allergic skin inflammation and promotes airway hyperreactivity and lung inflammation when combined with DNCB in NC/Nga mice.

Insects represent the largest and most diverse group of organisms on earth and are potential food and drug resources. Recently, we have demonstrated that a Forsythia viridissima extract prevented free fatty acid-induced lipid accumulation in an in vitro cellular nonalcoholic fatty liver disease (NAFLD) model. In this study, we aimed to evaluate the hepatoprotective effects of extracts of the insects Protaetia brevitarsis seulensis Kolbe, 1886 (PB), Oxya chinensis sinuosa Mishchenko, 1951 (OC), and Gryllus bimaculatus De Geer, 1773 (GB) in a high-fat diet (HFD)-induced NAFLD animal model, as well as to elucidate the underlying mechanisms. The effects of the supplementation with PB, OC, and GB extracts were evaluated histopathologically and histochemically. PB, OC, and GB extract supplementation inhibited the HFD-induced increase in body weight and body fat mass and ameliorated other adverse changes, resulting in decreased liver function parameters, lower serum triglyceride and cholesterol levels, and increased serum adiponectin levels. The expression of hepatic genes involved in lipid droplet accumulation and in fatty acid uptake also decreased upon treatment of HFD-fed mice with the extracts. These results provide evidence of the protective effects of the PB, OC, and GB extracts against HFD-induced fatty liver disease in an animal model.

Objective : This study aimed to evaluate the effects of Sagan-tang (SGT) on COPD mouse model.Methods : The study was carried out by two ways (in vitro, in vivo). In vitro RAW264.7 cells (mouse macrophage) were used and analysed by flow cytometry, ELISA, Western blot. In vivo LPS and CSS challenged mice were used and its BALF had been analysed by cytospin image, FACS, ELISA, lung tissue by real-time PCR.Results : In vitro, SGT maintained 80-100% rate of viablilty on 10 ~ 500 ㎍/㎖ concentration. In ELISA analysis with RAW264.7 cells, SGT significantly decreased NO over 30 ㎍/㎖. In flow cytometry, SGT 100 ㎍/㎖ dosage group displayed a tendency for decrease ROS. In Western blot analysis, SGT 100 ㎍/㎖ dosage group decreased NF-κB. In ELISA analysis, SGT significantly decreased TNF-α, IL-6 over 200 ㎍/㎖. In vivo SGT 200 ㎎/㎏ dosage group, application of SGT significantly decreased increase of neutrophils, TNF-α, IL-6 in BALF, muc5AC, TGF-β, TNF-α, expression of mRNA in lung tissue and histological lung injury.Conclusion : This Study suggests usability of SGT for COPD patients by controlling lung tissue injury.Key words : Sagan-tang (shegān-tāng), chronic obstructive pulmonary disease, cigarette smoke solution