• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1405-1410
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• 2005

Asthma is recognized today as an inflammatory disease of the lung characterized by acute non-specific airway hypersensitiveness in association with chronic pulmonary inflammation. Gamijihwang-tang(GJT), a fortified prescription of YMJHT, is applied for the treatments of chronic coughing and asthma, and post-delivery coughing and asthma in the gynecology. Also in the clinical practice, GJT is known to be very effective for controlling coughing and asthma as a cold sequoia. In this study, we investigated the effects of GJT on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production, and on the level of inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 expression in murine macrophage RAW 264.7 cells. We found that GJT inhibited LPS-induced NO and $PGE_2$ production in a dose dependent manner. Furthermore, GJT inhibited the expression of LPS-induced iNOS and COX-2 protein and mRNA expression in RAW 264.7 macrophages. Treatment with GJT of RAW 264.7 cells transfected with a reporter construct indicated a reduced level of LPS-induced nuclear factor-KB (NF-kB) activity and effectively lowered NF-kB binding as measured by transient transfection assay. These results suggest that the main inhibitory mechanism of the GJT may be the reduction of iNOS and COX-2 gene expression through blocking of NF-kB activation.

• Journal of Trauma and Injury
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• v.21 no.2
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• pp.120-127
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• 2008

Purpose: Many studies on the time course of inducible nitric oxide synthase (iNOS) gene expression have been performed in the LPS (Lipopolysaccharide)-induced endotoxemic model, but there have been few experimental approaches to continuous peritonitis-induced sepsis model. We conducted this study to establish basic data for future sepsis-related research by investigating the time course of iNOS gene expression and the relationship with the production of inflammatory mediators in the early sepsis model induced by cecal ligation and puncture (CLP). Methods: Male Sprague-Dawley rats were operated on by sing the CLP method to induce of peritonitis; and then, they were sacrificed and samples of blood and lung tissues were obtained at various times (1,2,3,6,9 and 12 h after CLP). We observed the expression of iNOS mRNA from lung tissues and measured the synthesis of nitric oxide, $IL-1{\beta}$, and $TNF-{\alpha}$ from the blood. Results: iNOS mRNA began to be expressed at 3 h and was maintained untill 12 h after CLP. The nitric oxide concentration was increased significantly at 6 h, reached its peak level at 9 h, and maintained a plateau untill 12 h after CLP. $TNF-{\alpha}$ began to be detected at 3 h, increased gradually, and decreased steeply from 9 h after CLP. $IL-1{\beta}$ showed its peak level at 6 h after CLP, and tended to decrease without significance. Conclusion: We observed that the iNOS gene was expressed later in peritonitis-induced sepsis than in LPS-induced sepsis. Nitric oxide and key inflammatory mediators were also expressed later in peritonitis-induced sepsis than in LPS-induced sepsis.

• BMB Reports
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• v.42 no.12
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• pp.794-799
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• 2009

The inhibition of nitric oxide (NO) and cyclooxygenase-2 (COX-2) production is considered to be a promising approach to the treatment of various diseases, including inflammation and cancer. In this study, we examined the effects of the Agrocybe chaxingu $\beta$-glucan (polysaccharide) on lipopolysaccaride (LPS)-induced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression in murine macrophage Raw 264.7 cells as well as 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. The polysaccharide significantly inhibited (P < 0.01) LPS-induced iNOS and COX-2 expression levels in the cells. Furthermore, topical application of polysaccharide resulted in markedly inhibited (P < 0.01) TPA-induced ear edema in mice. These results suggest that this polysaccharide may be used for NO- and COX-2-related disorders such as inflammation and cancer.

• Food Science and Biotechnology
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• v.16 no.5
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• pp.728-733
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• 2007

Bamboo grass, Sasa quelpaertensis, is a native plant to Jeju Island, Korea. The leaves of Sasa plants are widely used in traditional Korean medicine to treat inflammation-related diseases. We investigated the effect of hot water extract from Sasa quelpaertensis leaves (HWE-SQ) on nitric oxide (NO) production and nuclear $factor-{\kappa}B\;(NF-{\kappa}B)$ activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. HWE-SQ inhibited LPS-induced NO production and inducible NO synthase (iNOS) protein expression in a dose-dependent manner. Reporter gene assays indicated that HWE-SQ decreases LPS-induced $NF-{\kappa}B$ transcriptional activation. However, HWE-SQ did not affect the phosphorylation and degradation of inhibitory ${\kappa}B{\alpha}\;(1{\kappa}B{\alpha})$. HWE-SQ also directly inhibited iNOS enzyme activity in a dose-dependent manner. These results suggest that HWE-SQ suppresses NO synthesis in macrophages by attenuating $NF-{\kappa}B-mediated$ iNOS protein expression and inhibiting iNOS enzymatic activity, thereby implicating a mechanism by which HWE-SQ is able to ameliorate inflammation-related diseases by limiting excessive or prolonged NO production in pathological events.

• The Journal of Korean Medicine
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• v.19 no.2
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• pp.485-501
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• 1998

Cortex Mori (Moros alba L.), the root bark of mulberry tree has been used as an autiphlogistic, diuretic and expectorant in herval medicine. Recently, a few papers reported that phenolic extract of Cortex Mori had the hypotensive, hypoglycemic, antiviral and anticancer effects, and hot water extract of Cortex Mori(CM) had inhibitory effect on the degranulation and histamine release from activated mast cells. These previous studies suggest a possibility that CM has an antidotal activity against inflammation which was mediated mainly by macrophage-secreting inflammatory factors. This study was performed to evaluate the influences of CM on carrageenan-induced edema in vivo and release of inflammatory mediators such as NO, TNF and IL-1 by macrophages stimulated with LPS or $IFN-{\gamma}$ in vitro. Subcutaneous injections of carrageenan into the mouse paw rapidly induced local edema by increasing vascular permeability, but single intraperitoneal injection of CM extract at 30 minutes before carrageenan suppressed the development of edema. NO and TNF production from macrophage stimulated by LPS or $IFN-{\gamma}$ were significantly suppressed, especially TNF secretion by up to 3-4 folds. LPS stimulated IL-1 production was also inhibited, but not significantly. Cell viability assay verified that the inhibition was not due to general cell toxicity. These results suggest that reduction of NO, TNF and IL-1 production may be one of the means by which CM prevent inflammation associated diseases.

• Natural Product Sciences
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• v.22 no.1
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• pp.70-75
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• 2016

A phytoformula containing the root barks of Morus alba, the fructus of Schizandra sinensis and the roots of Asparagus cochinchinensis (MSA) was prepared as a potential new herbal remedy, and its therapeutic potential for alleviating inflammatory lung conditions was examined. For in vivo evaluation, an animal model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice was used. With oral administration of 6 - 60 mg/kg, MSA potently and dose-dependently inhibited bronchitis-like symptoms in acute lung injury induced by intranasal treatment of LPS as judged by the number of cells in the bronchoalveolar lavage fluid (BALF) and histological observation. The inhibitory potency was comparable with that of dexamethasone. For in vitro assay, the effects on the production of proinflammatory molecules in lung epithelial cells and alveolar macrophages were examined. Although MSA inhibited IL-6 production in IL-$1{\beta}$-treated lung epithelial cells (A549) only at a high concentration ($300{\mu}g/ml$), the formula strongly and concentration-dependently inhibited NO production in LPS-treated alveolar macrophages (MH-S) at $20-300{\mu}g/ml$. Based on all of these findings, the new phytoformula MSA is suggested to have the potential to control inflammatory lung diseases including bronchitis, at least in part, by inhibiting inducible nitric oxide synthase-catalyzed NO production.

• Journal of Applied Biological Chemistry
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• v.62 no.2
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• pp.111-122
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• 2019

The mulberry tree (Morus alba L.) has been traditionally used in Chinese medicine to treat inflammatory diseases. We investigated the effects of bioconversion on different components of the mulberry tree, and determined changes in the physiological activities. Ethyl acetate-soluble fractions of five different segments (fruit, Mori Fructus; leaf, Mori Folium; twig, Mori Ramulus; root, Mori Cortex; and mistletoe, Loranthi Ramulus) of the mulberry tree show enhanced anti-oxidant effects in the 2,2-diphenyl-1-picrylhydrazyl, and 2,2'-azinobis-(3-ethylvenzothiazoline-6-sulfonic acid) assays, and enhanced anti-inflammatory effects of lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW 264.7 macrophages, after being treated with a crude enzyme extract from Aspergillus kawachii, in the following order of activity: Mori Folium>Mori Cortex>Mori Ramulus>Mori Fructus>Loranthi Ramulus. Ethyl acetate- soluble fraction of mulberry leaves (Mori Folium) that underwent bioconversion was most effective, and was devoid of any cytotoxicity. The fraction was also effective against mRNA expression of LPS-induced pro-inflammatory cytokines, such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis $factor-{\alpha}$, $interleukin-1{\beta}$, and interleukin-6. In addition, the fraction was effective in LPS-induced phosphorylation of mitogen-activated protein kinases and IKK, and $I{\kappa}B$ degradation, followed by translocation of the nuclear $factor-{\kappa}B$ from the cytoplasm to the nucleus. Thus, bioconversion increased the anti-oxidative and anti-inflammatory activities of the mulberry leaf.

• Journal of Microbiology and Biotechnology
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• v.32 no.1
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• pp.15-26
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• 2022

Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1β, IL-6, IL-8 and IFN-β. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.3
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• pp.151-173
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• 2006

Purpose : This study was performed to evaluate anti-thrombotic and anti-inflammatory effects of BokbangHongdeungPaejangSan water extract (BHPS). Methods : BHPS was investigated using cultured cells and a murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells (mLFC) and RAW 264.7 cells. Results : In experiment of anti-thrombotic effect, BHPS inhibited the platelet aggregation induced by ADP and epinephrine, and inhibited pulmonary embolism induced by collagen and epinephrine. BHPS increased Platelet number and fibrinogen amount, and shortened PT and APTT in thrombus model induced by dextran. In experiment of anti-inflammatory effect, BHPS inhibited IL-1${\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II mRNA expression in a concentration-dependent manner in RAW 264.7 cell line, and inhibited significantly NO production at 50, 100 ${\mu}g/ml$, and also inhibited ROS production in a concentration-dependent manner. BHPS inhibited IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production significantly in serum of acute inflammation-induced Balb/c mice, and decreased IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production in spleen tissue, but increased IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production in liver tissue. BHPS increased survival rate at the 3th day in ICR mice with lethal endotoxemia induced by LPS. Conclusion : These results suggest that BHPS can be used for treating diverse female diseases caused by thrombosis and inflammation such as endometriosis, pelvic pain, cervicitis, pelvic inflammatory disease and pelvic tuberculosis and so forth.

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.3
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• pp.45-64
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• 2007

Purpose: This study was performed to evaluate anti-thrombotic and anti-inflammatory effects of NeungaSoJeokTang water extract (NSJT). Methods: In the study of anti-inflammatory effects, NSJT was investigated using cultured cells and murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells(mLFC) and RAW 264.7 cells. Results: Prior to the experiment, we evaluated sGOT, sGPT, BUN and creatine after the treatment. As a result, NSJT was innoxious on liver and kidney. In experiment of anti-thrombotic effect, NSJT inhibited the platelet aggregation induced by ADP and epinephrine, and inhibited pulmonary embolism induced by collagen and epinephrine. NSJT did not affect significantly the blood flow rate both in vitro and in vivo. NSJT increased platelet number and fibrinogen amount, and NSJT shortened PT and APTT in thrombus model induced by dextran. In experiment of anti-inflammatory effect, NSJT inhibited $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2 and NOS-II mRNA expression in a concentration-dependent manner in RAW 264.7 cell line, and inhibited significantly NO production at 50, 100 ${\mu}g/ml$, and also inhibited ROS production in a concentration-dependent manner. NSJT inhibited $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production significantly in serum of acute inflammation-induced Balb/c mice, and decreased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in spleen tissue, but increased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in liver tissue. NSJT increased survival rate at the 3th day in ICR mice with lethal endotoxemia induced by LPS. Conclusion: These results suggest that NSJT can be used for treating diverse female diseases caused by thrombosis and inflammation such as pelvic pain, pelvic inflammatory disease as well as vulvar pain due to vulvitis, vulvar vestibulitis and so on.