• Journal of Microbiology and Biotechnology
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• v.31 no.9
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• pp.1295-1304
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• 2021

Modified Renshen Wumei decoction (MRWD), a famous traditional Chinese medicine, is widely used for treating persistent diarrhea. However, as the mechanism by which MRWD regulates diarrhea remains unknown, we examined the protective effects of MRWD on intestinal barrier integrity in a diarrhea model. In total, 48 male rats were randomly distributed to four treatment groups: the blank group (CK group), model group (MC group), Medilac-Vita group (MV group) and Chinese herb group (MRWD group). After a 21-day experiment, serum and colon samples were assessed. The diarrhea index, pathological examination findings and change in ᴅ-lactate and diamine oxidase (DAO) contents illustrated that the induction of diarrhea caused intestinal injury, which was ameliorated by MV and MRWD infusion. Metabolomics analysis identified several metabolites in the serum. Some critical metabolites, such as phosphoric acid, taurine, cortisone, leukotriene B4 and calcitriol, were found to be significantly elevated by MRWD infusion. Importantly, these differences correlated with mineral absorption and metabolism and peroxisome proliferator-activated receptor (PPAR) pathways. Moreover, it significantly increased the expression levels of TLR4, MyD88 and p-NF-κB p65 proteins and the contents of IL-1 and TNF-α, while the expression levels of occludin, claudin-1 and ZO-1 proteins decreased. These deleterious effects were significantly alleviated by MV and MRWD infusion. Our findings indicate that MRWD infusion helps alleviate diarrhea, possibly by maintaining electrolyte homeostasis, improving the intestinal barrier integrity, and inhibiting the TLR4/NF-κB axis.

• Mass Spectrometry Letters
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• v.11 no.4
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• pp.71-76
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• 2020

While montelukast (ML), a cysteinyl-leukotriene type 1 receptor (CysLT1) antagonist is widely used to treat symptoms of rhinitis or asthma, its formulations are mainly limited to solid preparation due to its instability. Recently, there have been attempts to develop various ML dosage forms, and this situation increases the demand of sensitive and creditable methods to determine ML in various samples such as plasma. Thus, here, a simple and efficient method to determine ML in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was presented. The mixture of DCM:EtOAc (25:75, v/v), the optimized extract solvent for LLE was found to be effective to extract ML without hydrophilic salts and proteins from the sample with limited volume. Also, the use of zafirlukast, instead of expensive ML-d6, as the internal standard makes the present method economical. The developed method was successfully validated in terms of selectivity, matrix effects (-14.8--6.9%), linearity (r230.998 within 0.5-500 ng/mL), sensitivity (the limit of detection and the lower limit of quantitation, ≤0.5 ng/mL), accuracy (88.4-100.6%), precision (3.0-13.3%), and recovery (80.8-86.3%) by following the FDA guidelines. Finally, the applicability of the validated method to pharmacokinetics (PK) studies was confirmed by the successful determination of PK parameters through it following oral administration of Singulair® granule in rats. Therefore, the present method can contribute to the development of new ML formulations through its performance to determine ML in rat plasma efficiently and sensitively.

• Tuberculosis and Respiratory Diseases
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• v.85 no.1
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• pp.11-17
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• 2022

Background: In asthma, consistent control of chronic airway inflammation is crucial, and the use of asthma-controller medication has been emphasized. Our purpose in this study is to compare the incidence of acute exacerbation and healthcare costs related to the use of asthma-controller medication. Methods: By using data collected by the National Health Insurance Review and Assessment Service, we compared one-year clinical outcomes and medical costs from July 2014 to June 2015 (follow-up period) between two groups of patients with asthma who received different prescriptions for recommended asthma-controller medication (inhaled corticosteroids or leukotriene receptor antagonists) at least once from July 2013 to June 2014 (assessment period). Results: There were 51,757 patients who satisfied our inclusion criteria. Among them, 13,702 patients (26.5%) were prescribed a recommended asthma-controller medication during the assessment period. In patients using a recommended asthma-controller medication, the frequency of acute exacerbations decreased in the follow-up period, from 2.7% to 1.1%. The total medical costs of the controller group decreased during the follow-up period compared to the assessment period, from $3,772,692 to $1,985,475. Only 50.9% of patients in the controller group used healthcare services in the follow-up period, and the use of asthma-controller medication decreased in the follow-up period. Conclusion: Overall, patients using a recommended asthma-controller medication showed decreased acute exacerbation and reduced total healthcare cost by half.

• The Korea Journal of Herbology
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• v.32 no.3
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• pp.97-103
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• 2017

Objective : According to recent studies, Anemarrhenae Rhizoma has anti-inflammatory activities of DW extract, but it hasn't not yet conducted to evaluate inflammatory factors about 80% ethanol extract. Therefore, The aim of this study is to investigate the various effects of individual or combined 80% ethanol extract of Anemarrhenae Rhizoma on cell viability and various anti-inflammatory factors. Methods : Anemarrhenae Rhizoma extract was prepared with 80% ethanol. MTT assay, ELISA, and Luminex were performed in LPS-activated RAW 264.7 cell line to measure cytotoxicity, Nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 ($PGE_2$), Leukotriene B4 ($LTB_4$), and cytokines ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$), respectively. Results : At concentration of $200{\mu}g/m{\ell}$ Anemarrhenae Rhizoma extract, cytotoxicity was observed in RAW 264.7 cells. However, at concentration less than $100{\mu}g/m{\ell}$ of Anemarrhenae Rhizoma, cytotoxicity was not observed in RAW 264.7 cells. All concentration of Anemarrhenae Rhizoma extract showed no difference of NO, and $IL-1{\beta}$level in RAW 264.7 cells compared with control group. In contrast, at concentration of $100{\mu}g/m{\ell}$ Anemarrhenae Rhizoma extract significantly inhibited LPS-induced production of COX-2, PGE2, and $LTB_4$ level in RAW 264.7 cells. In addition, the production of proinflammatory cytokines (IL-6, $TNF-{\alpha}$) in LPS-induced RAW 264.7 cells was significantly decreased at concentration of all or 10, and $100{\mu}g/m{\ell}$, respectively. Conclusion : These findings demonstrate that Anemarrhenae Rhizoma has inhibitory effect on inflammatory mediators in LPS-activated RAW 264.7 cells showing possible developed as a raw material for new therapeutics to ease the symptoms related with inflammatory.

• Tuberculosis and Respiratory Diseases
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• v.63 no.4
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• pp.337-345
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• 2007

Backgrounds: Although glucocorticoids are one of the most potent anti-inflammatory agents, they have limited effect on cysteinyl leukotriene biosynthesis. In addition, the response to inhaled corticosteroids (ICS) and inhaled long-acting ${\beta}_2-agonists$ (LABA) combination therapy in moderate to severe persistent asthmatics varies. Additional therapy with leukotriene receptor antagonists (LTRA) in patients with moderate to severe asthma suboptimally controlled with ICS and LABA combination therapy would be complementary to asthma control. Methods: One hundred and ninety eight asthmatics entered a 2 month, open-label descriptive study. Patients suffering from persistent asthma and suboptimally controlled on a combination therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as an add-on therapy. The level of asthma control was assessed using the Asthma Control Questionnaire (ACQ) including $FEV_1%$ predicted at the baseline and after a 2-month treatment with montelukast. A global evaluation of the treatment was also made by the patients and physicians. Results: The mean ACQ score decreased significantly on montelukast ($11.5{\pm}5.4$ at baseline vs. $6.7{\pm}5.0$), with a significant improvement in all individual symptom scores (p<0.01). The $FEV_1%$ predicted values did not show any significant change. 59.9% of patients and 59.4% of physicians reported global improvement in their asthma (${\kappa}=0.85$). Conclusion: These results suggest that the addition of montelukast in patients with persistent asthma that is suboptimally contolled by combination therapy of ICS and LABA might confer complementary effects on asthma control.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.181-186
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• 2009

Purpose : Inflammation plays a potential role in the pathogenesis of bronchopulmonary dysplasia (BPD). Strategies for preventing BPD include respiratory management, antioxidants, nutritional treatment, and others such as anti-inflammatory agents. We aimed to assess the safety, tolerability, and efficacy of montelukast (MK), a cysteinyl leukotriene 1 receptor antagonist, as an add-on therapy in BPD. Methods : In addition to currently available standard measures such as oxygen supplementation, bronchodilators, nutritional support, and/or diuretics, montelukast was administered to 15 preterm infants with BPD. MK was given orally (1 mg/kg/d) for a mean period of 12 weeks. We compared safety and efficacy parameters with historical controls. Results : All 15 patients survived, and no differences were found in the incidence of adverse reactions between the 2 groups. The ventilation index was significantly improved after 2 weeks in MK group compared with historical controls. There were no significant differences in other respiratory parameters (MAP, oxygen dependency, and ventilator dependency) between the groups, but the MK group showed trends of greater improvement. Conclusion : Administration of MK 1 mg/kg/d was well tolerated in preterm BPD patients as an add-on therapy. We demonstrated that after 2 weeks of MK administration of 1 mg/kg/d, MK had beneficial therapeutic effects on BPD patients as an add-on to the standard therapy. Further multicenter randomized controlled clinical trials are needed to confirm the efficacy and safety of MK as a useful supplement to standard therapy for BPD patients.

• Journal of Life Science
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• v.21 no.6
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• pp.767-774
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• 2011

Cell migration plays a fundamental role in cancer cell invasion and metastasis as well as in many physiological responses. Here, we screened four different sources of garlic - water extract of normal and black garlic, as well as dried normal and black garlic - for the identification of anti-invasive and anti-metastatic activity on cancer cells. Inhibition of cancer cell migration was observed in the hexane extract of dried-garlic. Inhibitory activity was further purified to near homogeneity by thin layer chromatography and named $\b{i}$nhibitor of $\b{c}$ancer $\b{m}$etastasis from garlic #27 (ICMG-27). ICMG-27 completely blocked insulin-like growth factor-1 (IGF-1)-induced OVCAR-3 cell migration at 6 ${\mu}g/ml$. ICMG-27 completely blocked IGF-1-induced OVCAR-3 and NIH-3T3 cell migration whereas IGF-1-induced mouse embryonic fibroblast (MEF) cell migration was not affected byICMG-27. ICMG-27 inhibited all the tested IGF-1-induced cancer cell migration such as OVCAR-3, SKOV-3, and MDA-MB-231 cells. Finally, ICMG-27 could inhibit IGF-1-, lysophosphatidic acid (LPA)-, sphingosine-1-phosphate (S1P)-, leukotriene B4 (LTB4)-, and angiotensin II (AngII)-induced OVCAR-3 cell migration. These results indicate that ICMG-27 inhibits cancer cell migration by blocking essential steps in many agonists-induced cancer cell migrations. Unveiling an anti-invasive mechanism of ICMG-27 on cancer cells will provide a basis for cancer therapy.

• Tuberculosis and Respiratory Diseases
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• v.39 no.4
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• pp.304-309
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• 1992

Background: The alveolar macrophage may metabolize arachidonic acid through cyclooxygenase- and lipoxygenase- catalyzed pathways to produce a variety of metabolites of arachidonic acid. The production of these metabolites of arachidonic acid may enhance the defensive ability of the challenged lung. However, continued stimulation with the consequent production of proinflammtory metabolites of arachidonic acid, may ultimately enhance the disease process by contributing to chronic bronchoconstriction, fibrosis, and the persistent release of toxic oxygen species. Silicosis is an example of a disease process resulting from chronic exposure of the lung to foreign particles. This study was carried out to evaluate the changes of arachidonic acid metabolites from macrophages in experimental silicosis. Methods: We measured $PGE_2$, and $LTB_4$ in cultured macrophages taken from rats by radioimmunoassay at 24 and 48 hours after stimulation by silica dust, natural carbon dust, lipopolysaccharide, calcium ionophore (A23187) and medium (RPMI) as a control. For the experimental silicosis, 50 mg silica in 0.5 ml saline was administered intratracheally into the rat and grown to 20 weeks and measured $PGE_2$, and $LTB_4$ in the cultured macrophages lavaged from that rat. The used stimulants were the same as above. Results: 1) The amount of $PGE_2$ in the cultred macrophages from normal rat was significantly decreased in the group which was stimulated with silica dust for 48 hours compare with control non-stimulated group. 2) In the experimental silicosis group, $PGE_2$, release in cultured macrophages after 48 hours incubation with silica and natural carbon dust tended to be lower than those of non-stimulated group. 3) There were marked changes of $LTB_4$ in the groups of normal rats which were incubated with silica for 24, 48 hours and natural carbon for 48 hours compared with non-stimulated group. 4) In the experimental silicosis group, the release of $LTB_4$ was significantly increased macrophages cultured with silica and natural carbon dust after 24 and 48 hours incubation compared with non-stimulated group. Conclusion: The results of these studies suggest that the in vitro exposure of rat alveolar macrophge to silica and coal dust results in an alteration in alveolar macrophage metabolism of arachidonic acid that may promote an inflammatory reaction in lung tissue.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.369-379
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• 1998

Background: Platelet-activating factor(PAF) might play an important role in the development of acute respiratory distress syndrome. Since PAF induced lung injury is similar to changes of acute respiratory distress gyndrome, and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of PAF on the regulation of surfactant protein A, B and C mRNA accumulation Method: The effects of PAF on gene expression of surfactant protein A, B and C in 24 hours after intratracheal injection of PAF in rats. Surfactant protein A, B and C mRNAs were measured by filter hybridization. Results: The accumulation of SP-A mRNA in PAF treated group was significantly decreased by 37.1 % and 41.6%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.025, p<0.01). The accumulation of SP-B mRNA in PAF treated group was decreased by 18.7% and 32.2 %, respectively compared to the control group and the group treated with Lyso-PAF but statistically not significant. The accumulation of SP-C mRNA in PAF treated group was significantly decreased by 30.7% and 38.5%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.l, p<0.01). Conclusion: These findings represent a marked inhibitory effects of platelet-activating factor on surfactant proteins expression in vivo. This supports, in turn, 'platelet-activating factor might be related to pathogenesis of acute respiratory distress syndrome.

• The Journal of Korean Medicine
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• v.34 no.1
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• pp.116-135
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• 2013

Objectives: This study was intended to clarify how Jakyakkamchobuja-tang (hereinafter referred to JKBT) affects mice of C57BL/10 whose osteoarthritis was induced by papain. Methods: Osteoarthritis was induced in mice by injecting papain in the knee joint. Mice were divided into 4 groups (n=6). The normal group were not treated at all whereas the control group (OAC-control) were induced for osteoarthritis by papain and oral medicated with 200 ul of physiological saline per day. The positive comparison group (OAC-$Joins^{(R)}$) were injected with papain and after 7 days, 100 mg/kg of $Joins^{(R)}$ were medicated with 200 ul of physiological saline mixed. The experimental group (OAC-JKBT) were injected with papain and after 7 days were medicated with 400 mg/kg of JKBT mixed with 200 ul of physiological saline. OAC-$Joins^{(R)}$ and OAC-JKBT were oral medicated for each substance for a total of 4 weeks, once per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the function of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological variations for knee joint structures were observed. Results: Functions of liver and kidney were not affected. IL-$1{\beta}$ (interleukin-$1{\beta}$), MCP-1 (monocyte chemoattractant protein-1) and TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) were significantly reduced and IL-6 (interleukin-6) was also reduced but not significantly. After analyzing inflammation cytokine in joints with mRNA (messenger ribonucleic acid), revelation of IL-6, TNF-${\alpha}$, COX-2 (cyclooxygenase-2) and iNOS-II (inducible nitric oxide synthase-II) were all significantly reduced. Revelation of IL-$1{\beta}$ gene was also reduced but not significantly. Neutrophil for WBC (white blood cell) within serum was significantly reduced; monocyte was also reduced but not significantly. PGE2 (prostaglandin E2), TXB2 (thromboxane B2) were significantly reduced and LTB4 (leukotriene B4) was also reduced but not significantly. Destruction of cartilage on micro CT (computed tomography)-arthrography was reduced but had no significant differences. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small (H&E (hematoxylin and eosin), safranine O staining). Conclusions: Based on these results, Jakyakkamchobuja-tang (JKBT) is believed to be useful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.