• Parasites, Hosts and Diseases
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• 제48권4호
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• pp.285-290
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• 2010

Tyrosine kinases are one of the most important regulators for intracellular signal transduction related to inflammatory responses. However, there are no reports describing the effects of tyrosine kinases on neutrophil apoptosis induced by Entamoeba histolytica, In this study, isolated human neutrophils from peripheral blood were incubated with live trophozoites in the presence or absence of tyrosine kinase inhibitors. Entamoeba-induced receptor shedding of CD16 and PS externalization in neutrophils were inhibited by pre-incubation of neutrophils with the broad-spectrum tyrosine kinase inhibitor genistein or the Src family kinase inhibitor PP2. Entamoeba-induced ROS production was also inhibited by genistein or PP2, Moreover, genistein and PP2 blocked the phosphorylation of ERK and p38 MAPK in neutrophils induced by E. histolytica. These results suggest that Src tyrosine kinases may participate in the signaling event for ROS-dependent activation of MAPKs during neutrophil apoptosis induced by E. histolytica.

• Nutrition Research and Practice
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• 제8권1호
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• pp.11-19
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• 2014

Synurus deltoides (Aiton) Nakai, belonging to the Compositae family, is an edible plant widely distributed in Northeast Asia. In this study, we examined the mechanisms underlying the immunomodulative effects of the ethanol extract of S. deltoides (SDE). The SDE extract strongly down-regulated the mRNA expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumour necrosis factor (TNF)-${\alpha}$, thereby inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2), and TNF-${\alpha}$ in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, SDE also suppressed the nuclear translocation of the activation protein (AP)-1 and the nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and simultaneously decreased the phosphorylation of extracellular signal-regulated protein kinases (ERK), p38, and Akt. In agreement with the in vitro observations, the orally administered SDE ameliorated the acute inflammatory symptoms in the arachidonic acid-induced ear edema and the EtOH/HCl-induced gastritis in mice. Therefore, S. deltoides have a potential anti-inflammatory capacity in vitro and in vivo, suggesting the potential therapeutic use in the inflammation-associated disorders.

• International Journal of Oral Biology
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• 제39권4호
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• pp.221-228
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• 2014

Glucosamine is commonly taken by the elderly without prescription as a nutritional supplement to attenuate the progression or symptoms of osteoarthritis. Previous studies demonstrated that glucosamine shows anti-inflammatory effects in tissues such as blood vessels and the heart. However, there have been few reports about the effects of glucosamine on oral inflammatory diseases. Therefore, in this study, the effects of glucosamine on lipopolysaccharide (LPS)-induced inflammatory responses were investigated using human periodontal ligament fibroblasts (HPDLFs). HPDLFs were incubated in the presence and absence of glucosamine (10 mM) for 24 h, followed by treatment with E. coli LPS (100 ng/ml) or vehicle. Quantitative RT-PCR and ELISA results showed that LPS exposure significantly increased the levels of IL-6 and IL-8 mRNA and protein, while the effect was significantly suppressed by glucosamine treatment. Glucosamine did not attenuate, but slightly increased, the LPS-induced activation of mitogen activated kinases (ERK, p38, JNK). However, it suppressed the LPS-induced increase in the DNA binding affinity and transcriptional activity of NF-${\kappa}B$. These results suggest that glucosamine exerts anti-inflammatory effects on HPDLFs exposed to LPS via inhibition of NF-${\kappa}B$ activity, necessitating further studies using animal periodontitis models.

• BMB Reports
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• 제47권2호
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• pp.98-103
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• 2014

Orostachys japonicus shows various biological activities. However, the molecular mechanisms remain unknown in LPS-stimulated macrophages. Here, we investigated the anti-oxidizing effect of the dichloromethane (DCM) and hexane fractions from O. japonicus (OJD and OJH) against oxidative stress in RAW 264.7 cells stimulated by LPS. OJD and OJH significantly increased the expression of heme oxygenase-1 (HO-1) in a dose- and time-dependent manner. Additionally, it was found that the expression of HO-1 was stimulated by Nrf2 activated via degradation of Keap1. ERK and p38 inhibitors repressed HO-1 induced by OJD and OJH in LPS-stimulated cells, respectively. In conclusion, these results suggest that OJD and OJH may block oxidative damage stimulated by LPS, via increasing the expression of HO-1 and Nrf2, and MAPK signaling pathway.

• 대한한의학회지
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• 제25권3호
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• pp.90-98
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• 2004

Objectives : The present study was undertaken to investigate the molecular mechanisms of Ichungwhan for inhibition of cyclooxygenase-2 (COX-2) gene expression via suppression of NF-κB (nuclear factor κB) using aged rats. NF-κB is the most important modulator of inflammation and NF-κB regulates the gene expression of several pro-inflammatory cytokines, such as COX-2. Methods : In the experiment, we investigated the scavenging property of Ichungwhan on reactive species (RS) including nitrogen-derived species (RNS), measured by DCF-DA (2,7-dichlorodihydrofluorexcein diacetate) / DHR 123 (dihydrorhodamine 123) assay. Protein expression levels of COX-2, NF-κB, p-ERK and p-p38 were assayed by western blot. Results : We showed that Ichungwhan inhibits RS including RNS and inhibits NF-κB activation by blocking the dissociation of inhibitory IκB-β via suppression of IKK pathway. Also, Ichungwhan inhibits COX-2 gene expression. Conclusions : These findings suggest that Ichungwhan modulates COX-2 gene expression via suppression of the NF-κB pathway.

• 동의생리병리학회지
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• 제24권3호
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• pp.410-415
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• 2010

The purpose of this study was to investigate the anti-inflammatory effects of aqueous extract from Belamcanda chinensis (BC) on the RAW 264.7 cells. To evaluate the anti-inflammatory effects of BC, we examined the cytokine productions including nitric oxide (NO), interleukin (IL)-1b, IL-6 and tumor necrosis factor-a (TNF-a) in lipopolysaccharide (LPS)-induced RAW 264.7 cells and also inhibitory mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kB) using Western blot. BC inhibited LPS-induced production of NO, IL-6 and TNF-a but not of IL-1b in RAW 264.7 cells. BC respectively inhibited the activation of MAPKs such as c-Jun NH2-terminal kinase (JNK) and p38 but not of extracelluar signal-regulated kinase (ERK 1/2) and NF-kB in the LPS-stimulated RAW 264.7 cells. Taken together, Our results showed that BC down-regulated LPS-induced NO, IL-6 and TNF-a productions mainly through JNK and p38 MAPK pathway.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 춘계학술발표회
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• pp.106-106
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• 2018

Cyanidin 3 - rutinoside chloride (CRC) is major anthocyanin, found in Schisandra chinensis, is known to have antioxidant, anticancer, anti-inflammatory, tonic, and anti-aging effects in Korea, China and Japan. In the present study, the human mast cell line (HMC-1) was used to investigate the effects on the production of pro-inflammatory mediators. In this study, CRC showed no cytotoxicity in HMC-1. CRC significantly inhibited the secretion of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6 in PMA plus A23187 cacium ionophore (PMACI)-stimulated HMC-1 cells. In addition, CRC suppressed the serum levels of IgE. Furthermore, CRC decreased the PMACI- stimulated phosphorylation of mitogen activated protein kinases (MAPKs) such as p-ERK, p- JNK and p-P38. These results indicate that the pharmacological actions of CRC suggest their potential activity for treatment of allergic inflammation through the down-regulation of mast cell activation.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.88.3-89
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• 2003

Acanthoic acid (AA) is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum (Araliaceae), which has been traditionally used as a tonic and sedative as well as in the treatment of rheumatism and diabetes in korea. Proteinase-activated receptor-2 (PAR-2) agonist trypsin plays a role in inflammation, and human leukemic mast cells (HMC-l) express PAR-2. In the present study, the effect of acanthoic acid on production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and tryptase in trypsin-stimulated HMC-1 was examined. (omitted)

• BMB Reports
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• 제51권3호
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• pp.119-125
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• 2018

The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis of YAP expressions can facilitate the identification of patients who respond better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted inhibitors. The prominence of YAP for those aspects of cancer biology denotes that these factors are ideal targets for the development of anti-cancer medications. Therefore, our report strongly indicates that the YAP is of potential prognostic utility and druggability in various human cancers.

• Journal of Ginseng Research
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• 제32권2호
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• pp.89-98
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• 2008

There are increasing evidences in the literatures on the potential role of ginsenosides in treating cardiovascular diseases. In this article, current information about ginsenosides-mediated vascular relaxation are reviewed. From the published studies using isolated organs, cell culture systems and animal models, ginsenosides are shown to relax blood vessels and improve blood flow through diverse mechanisms, including nitric oxide release by activating eNOS phosphorylation via PI3K/Akt and/or ERK1/2 pathways in endothelial cells, induction of inducible nitric oxide synthase through activation of NF-${\kappa}$B, reducing the intracelluar Ca$^{2+}$ levels by activating Ca$^{2+}$-activated K$^{+}$ channels in vascular smooth muscle cells and reducing platelet aggregation by decreasing thromboxane A$_2$ formation and intracelluar Ca$^{2+}$in platelets. In addition, the relevant clinical trials regarding the effects of ginsenosides on the cardiovascular disease are summarized, particulary focusing on managing hypertension and improving thrombotic disorders. Finally, antagonistic effects of ginsenosides on the prostaglandin H$_2$ receptor and scavenging effects on the generation of oxygen-derived free radicals in spontaneously hypertensive rats (SHR) are discussed.