• Archives of Pharmacal Research
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• v.28 no.4
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• pp.395-399
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• 2005

From $70\%$ ethanol extract of the roots of Smilax bockii warb., seven flavonoids, kaempferol (1), $kaempferol-7-O-\beta-D-glucopyranoside$ (2), quercetin (3), isorhamnetin (4), (+)-dihydro­kaempferol (5), engeletin (6), isoengeletin (7), and $n-butyl-\beta-D-fructopyranoside$ (8), caffeic acid n-butyl ester (9) were isolated and identified by means of chemical and spectroscopic. Compounds 2, 4, and 6-9 were isolated for the first time from the roots of S. bockii and compounds 2, 8, and 9 were firstly isolated from the genus Smilax. In addition, using the SEAP (Secreted alkaline phosphatase) assay system, we investigated the in vitro anti-inflammatory activity of the $70\%$ ethanol extract of the roots of S. bockii, which showed moderate activity in inhibiting $TNF-\alpha-induced NF-{\kappa}B$ activation with an $IC_{50}$ value of $166.6 {\mu}g/mL$.

• YAKHAK HOEJI
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• v.57 no.6
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• pp.394-399
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• 2013

In this study we demonstrated whether the extract of Polygonum aviculare L. (PAE) can be applied to the immune-stimulating responses in macrophages (Raw 264.7 cells). Cell viability was determined by WST-8 assay, and all four doses of PAE (5, 10, 20, and 40 ${\mu}g/ml$) had no significant cytotoxicity during the entire experimental period. PAE increased the production of inducible nitric oxide synthase (iNOS) and nitric oxide (NO), and mRNA expressions and protein levels of pro-inflammatory cytokines(tumor necrotic factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6) in the same cells. These immune-stimulating activities of PAE were found to be caused by the stimulation of $NF{\kappa}B$ signal and phosphorylation of MAP kinases (p38, ERK and JNK).

• Applied Biological Chemistry
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• v.51 no.1
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• pp.44-48
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• 2008

With extracts from Cheongmoknosang, anti-inflammatory effect was examined in LPS-stimulated Raw 264.7 cells. LPS (10 ng/ml) treatment increased the production of inflammatory cytokines, $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ but the ethanol extracts from Cheongmoknosang slightly decreased the production of $TNF-{\alpha}$ and also reduced the expression of iNOS and the production of COX-2. It seems that anti-inflammatory effects of ethanol extracts from Cheongmoknosang is partly due to the inhibition of iNOS and COX-2 expression by inhibiting nuclear translocation of $NF-{\kappa}B$ and AP-l in Raw 264.7 cells.

• Natural Product Sciences
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• v.22 no.1
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• pp.13-19
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• 2016

In this report, we investigated the antioxidant (peroxyl radical-scavenging and reducing capacities) and anti-osteoporotic activities of extracts and isolated constituents (1 - 16) from the rhizomes of Kaempferia parviflora Wall. ex Baker on pre-osteoclastic RAW 264.7 cells. Compound 5 exhibited significant peroxyl radical-scavenging capacity, with TE value of $8.47{\pm}0.52{\mu}M$, while compound 13 showed significant reducing capacity, with CUPRAC value of $5.66{\pm}0.26{\mu}M$, at $10.0{\mu}M$. In addition, flavonoid compounds 2, 4, 6, 8, 10, 12, and terpene compound 15 showed significant inhibition of tartrate-resistant acid phosphatase (TRAP) in NF-${\kappa}B$ ligand-induced osteoclastic RAW 264.7 cells, with values ranging from $16.97{\pm}1.02$ to $64.67{\pm}2.76%$. These results indicated that K. parviflora could be excellent sources for the antioxidant and anti-osteoporotic traditional medicinal plants.

• Parasites, Hosts and Diseases
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• v.54 no.5
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• pp.679-684
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• 2016

Clonorchiasis, caused by direct contact with Clonorchis sinensis worms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated by C. sinensis ESPs cause NF-${\kappa}B$-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiating C. sinensis infection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.

• Molecules and Cells
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• v.40 no.5
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• pp.371-377
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• 2017

Despite the importance of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-RANK signaling mechanisms on osteoclast differentiation, little has been studied on how RANK expression is regulated or what regulates its expression during osteoclastogenesis. We show here that insulin signaling increases RANK expression, thus enhancing osteoclast differentiation by RANKL. Insulin stimulation induced RANK gene expression in time- and dose-dependent manners and insulin receptor shRNA completely abolished RANK expression induced by insulin in bone marrow-derived monocyte/macrophage cells (BMMs). Moreover, the addition of insulin in the presence of RANKL promoted RANK expression. The ability of insulin to regulate RANK expression depends on extracellular signal-regulated kinase 1/2 (ERK1/2) since only PD98059, an ERK1/2 inhibitor, specifically inhibited its expression by insulin. However, the RANK expression by RANKL was blocked by all three mitogen-activated protein (MAP) kinases inhibitors. The activation of RANK increased differentiation of BMMs into tartrate-resistant acid phosphatase-positive ($TRAP^+$) osteoclasts as well as the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of vacuolar ($H^+$) ATPase (v-ATPase) Vo domain (Atp6v0d2), genes critical for osteoclastic cell-cell fusion. Collectively, these results suggest that insulin induces RANK expression via ERK1/2, which contributes to the enhancement of osteoclast differentiation.

• Journal of Radiation Industry
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• v.4 no.3
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• pp.227-231
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• 2010

The purpose of this study was to investigate the expression mechanism of MCP-1 in gamma-irradiated RAW 264.7 macrophage cells. MCP-1 plays an important role in attracting monocyte to injured site at the early inflammation stage. However the production mechanism of MCP-1 by gamma-irradiation in RAW 264.7 macrophage cells was almost undiscovered. We found that MCP-1 was produced in RAW 264.7 macrophage cells by irradiation with 5 Gy. And these inceases were attenuated by specific inhibitors treatment, such as $NF-{\kappa}B$, JNK, ERK, JAK2, and Pyk2. These results indicate that radiation-induced MCP-1 production is mediated by MyD88- and TRIF-dependent pathways in RAW 264.7 macrophage cells. Furthermore, gamma-irradiation induced heme oxygenase-1 (HO-1) expression in RAW 264.7 macrophage cells. However this induction level was reduced before MCP-1 and $IFN-{\beta}$ production.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.501-508
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• 2019

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and $NF-{\kappa}B$ p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of $CD4^+/CD8^+$ and the secretion of interleukin (IL)-2 and interferon-${\gamma}$, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.123-123
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• 2019

Xanthone is a kind of polyphenolic compounds that contain a distinctive chemical structure with a tricyclic aromatic ring found in a few higher plant families e.g. gentian root. This compound had a variety of biological activity, for instance antioxidant, antibacterial, anti-inflammatory, and anticancer effects. However, the effect of xanthone on mast cell-mediated allergic inflammation and its associated mechanism have not been elucidated. Therefore, the aim of this study was to elucidate the anti-allergic inflammatory effects and the underlying molecular mechanism of xanthone in PMACI-stimulated human mast cells-1 (HMC-1). In this result, xanthone treatment decreased the production of histamine, pro-inflammatory cytokines such as tumor necrosis factor-a (TNF-${\alpha}$), IL-6, and IL-8 and expressions of TSLP in PMACI-stimulated HMC-cells. In addition, xanthone significantly suppressed the phosphorylation of MAPKs and the activation of NF-${\kappa}B$ signal pathway in activated mast cells. Furthermore, xanthone inhibited the activation of caspase-1, an IL-$1{\beta}$ converting enzyme, in PMACI-stimulated HMC-1 cells. These findings provide evidence that xanthone could be a potential therapeutic agent for allergy-related inflammatory disorders.

• Biomedical Science Letters
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• v.25 no.1
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• pp.60-65
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• 2019

Toll-like receptors (TLRs) are one of the families of pattern recognition receptors (PRR) operating in the innate immunity. TLRs have the ability to recognize relatively conserved microbial components, which are generally referred to as pathogen-associated molecular patterns (PAMPs). The activation of TLRs signaling leads to the activation of $NF-{\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of pristimerin, which is a naturally occurring triterpenoid compound from Celastraceae plants, iNOS expression induced by MALP-2 (TLR2 and TLR6 agonist), Poly[I:C] (TLR3 agonist), or LPS (TLR4 agonist) were examined. Pristimerin suppressed the iNOS expression induced by MALP-2, Poly[I:C], or LPS. These results suggest that pristimerin can modulate TLRs signaling pathways leading to decreased inflammatory gene expression.