• The Journal of Korean Medicine
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• v.40 no.3
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• pp.35-58
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• 2019

Objectives: The aim of this study was to investigate the anti-inflammatory effects of Curcuma longa rhizoma extract in an experimental rat model of osteoarthritis. Methods: Osteoarthritis was induced in rats by injecting monosodium iodoacetate (MIA) into the knee joint cavity of rats. The rats were divided into 5 groups (Normal, Control, positive comparison, low (CL) and high (CH) concentration groups). Rats in the low concentration (CL) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 50mg/kg body weight. Rats in the high concentration (CH) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 100mg/kg body weight. Hind paw weight distribution and ROS levels were measured. At the end of all treatments, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels were analyzed. In addition, inflammatory protein levels were evaluated by western blot analysis. Results: In this study, hind paw weight distribution significantly improved in the CL and CH groups, while. Reactive oxygen species (ROS) production significantly decreased in both. The levels of ALT, AST, BUN, and creatinine did not significantly change in either group. The production of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), $p47^{phox}$, and Ras-related C3 botulinum toxin substrate 1 (RAC1) decreased in both. Catalase, heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) significantly increased in the CL and CH groups, respectively. Nuclear factor erythroid 2 (Nrf2) increased, but there were no significant differences between the experimental and control groups. Inflammatory cytokines, including nuclear factor-kappa Bp65 (NF-${\kappa}Bp65$), interleukin-1beta (IL-$1{\beta}$), and tumor necrosis factor-alpha (TNF-${\alpha}$), decreased significantly in both the CL and CH groups. Conclusions: Our results showed that Curcuma longa rhizoma extract has anti-inflammatory effects. Anti-inflammatory activity is regulated by the inhibition of inflammatory cytokines and mediators, such as NF-${\kappa}B$, therefore, it suppresses cartilage damage as well.

• Journal of Acupuncture Research
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• v.24 no.6
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• pp.15-27
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• 2007

Objectives : The purpose of this study is to investigate the effectiveness of Ulmus davidiana Planch herbal acupuncture(UA) to inhibit nuclear $factor(NF)-{\kappa}B$ activation on type II collagen-induced arthritis (CIA) in mice. Methods : Using an in vitro test, the synoviocytes picked out from the experimental CIA mice were subcultured. The synoviocyte cells were treated with phorbol-12-myristate-13-acetate(PMA) for 1 hour prior to the addition of indicated concentrations($0.4\;-\;1.0mg/m{\ell}$) of UA, and the cells were further incubated for 24 hours. The in vivo test, $NF-{\kappa}B$ p65, inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), vascular cell adhesion molecule(VCAM)-1 production and apoptosis was observed by immunohistochemical staining. Results : The PMA-induced $I{\kappa}B$ kinase(IKK), iNOS and COX-2 mRNA expression were dose-dependently decreased in UA treated synoviocytes. Using the in vivo test, the number of eosinophils in mice treated with UA noticeably decreased in the the CIA group(P<0.05 using student t test). In mice treated with UA, there was less cartilage erosion. less bone destruction, mild synovial hyperplasia, mild fibrosis, and mild angiogenesis with less MIP-2 production. By immunohistochemical staining, suppression of $NF-{\kappa}B$ p65, iNOS production, inhibition of COX-2 production, inhibition of VCAM-1 production and inducing apoptosis were observed. Conclusions : These results suggest that UA might be applicable to the therapy of RA to suppress $NF-{\kappa}B$ activation.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.3
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• pp.20-31
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• 2019

Objectives: The seeds from Arctium lappa have been considered for its various pharmacological properties, which include anti-carcinogenic, anti-inflammatory, anti-diabetic, and anti-viral activities. Methods: In the present study, we investigated the anti-inflammatory effect of the ethanol extract from the seeds of Arctium lappa L (EAL) on cytokine-induced vascular inflammation in human umbilical vein endothelial cells (HUVEC). Results: Pretreatment with EAL significantly decreased tumor necrosis factor alpha ($TNF-{\alpha}$)-induced cell adhesion molecules expression such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) in a dose-dependent manner. Cell adhesion assay showed that pretreatment with EAL suppressed HUVEC-monocyte adhesion by $TNF-{\alpha}$ over $1{\mu}g/ml$ concentration. We investigated the involvement of nuclear transcription factor kappa-B ($NF-{\kappa}B$) in $TNF-{\alpha}$-induced vascular inflammation. $NF-{\kappa}B$ p65 nuclear expression was induced by $TNF-{\alpha}$, however, pretreatment with EAL was attenuated that nuclear translocation. In cytoplasm, EAL was also attenuated $TNF-{\alpha}$-induced decrease of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$) expression. Moreover, EAL significantly decreased $TNF-{\alpha}$-induced production of intracellular reactive oxygen species (ROS). Conclusions: Taken together, our findings suggest that seeds of Arctium lappa L could be a therapeutic herb for prevention of cardiovascular diseases throughout the inhibition of vascular endothelial inflammation.

• Molecules and Cells
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• v.23 no.3
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• pp.398-404
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• 2007

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in various pathophysiological processes such as inflammation and carcinogenesis. In a search for inhibitors of COX-2 and iNOS production we found that extracts of Stewartia koreana strongly inhibited NO and $PGE_2$ production in LPS-treated macrophage RAW 264.7 cells. We have now shown that the mRNA and protein levels of iNOS and COX-2 are reduced by the Stewartia koreana extract (SKE). SKE inhibited expression of an NF-${\kappa}B$ reporter gene in response to LPS, and gel mobility shift assays revealed that SKE reduced NF-${\kappa}B$ DNA-binding activity. The extract also inhibited LPS-induced phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Administration of the extract reduced the symptoms of arthritis in a collagen-induced arthritic mouse model. These results indicate that Stewartia extracts contain potentially useful agents for preventing and treating inflammatory diseases.

• BMB Reports
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• v.54 no.11
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• pp.545-550
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• 2021

Anisomycin is known to inhibit eukaryotic protein synthesis and has been established as an antibiotic and anticancer drug. However, the molecular targets of anisomycin and its mechanism of action have not been explained in macrophages. Here, we demonstrated the anti-inflammatory effects of anisomycin both in vivo and in vitro. We found that anisomycin decreased the mortality rate of macrophages in cecal ligation and puncture (CLP)- and lipopolysaccharide (LPS)-induced acute sepsis. It also declined the gene expression of proinflammatory mediators such as inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-1β as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-κB activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-κB-inducing kinase and IκB kinase, phosphorylation and IκBα proteolytic degradation, and NF-κB p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-κB-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.

• Molecules and Cells
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• v.37 no.12
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• pp.899-906
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• 2014

Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

• Korean Journal of Food Science and Technology
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• v.53 no.2
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• pp.154-159
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• 2021

Barringtonia augusta Kurz is a species of the genus Barringtonia. Although several studies have analyzed the biological activity of B. racemosa Roxb and B. acutangula, the anti-inflammatory and antioxidant effects of B. augusta extract (BKE) remain unclear. Therefore, in this study, we investigated the anti-inflammatory and antioxidant effects of BKE using lipopolysaccharide (LPS) and RAW 264.7. BKE suppressed LPS-induced nitric oxide (NO) and inducible NO synthase expression without affecting RAW 264.7 cell viability. Additionally, BKE showed 2,2-Diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging capacities and inhibited LPS-induced reactive oxygen species production in RAW 264.7 cells. BKE also suppressed LPS-induced phosphorylation of IκB kinase and nuclear factor kappa-B (NF-κB) and p65 translocation from the cytosol to the nucleus in RAW 264.7 cells. These results suggest that BKE is a possible novel material that exerts beneficial antioxidant and anti-inflammatory effects through the inhibition of NF-κB signaling pathways.

• YAKHAK HOEJI
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• v.60 no.3
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• pp.128-134
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• 2016

L1 cell adhesion molecule (L1CAM) is a cell surface molecule to initiate a variety of cellular responses through interacting with other cell adhesion molecules in a homophilic or heterophilic manner. Although its expression was found to be upregulated in some tumor cells, including cholangiocarcinomas, and ovarian cancers, and many studies have investigated the role of L1CAM in these cancers, its role in inflammatory responses has been poorly understood. In this study, we explored the role of L1CAM in macrophage-mediated inflammatory responses. L1CAM significantly suppressed the production of nitric oxide (NO), but induced cell proliferation in RAW264.7 cells. L1CAM expression was detectable, but its expression was markedly decreased by lipopolysaccharide (LPS) in RAW264.7 cells. In addition, the expression of pro-inflammatory genes, such as tumor necrosis factor (TNF)-${\alpha}$, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) induced by LPS was dramatically suppressed by L1CAM in RAW264.7 cells. L1CAM inhibited the transcriptional activities of NF-${\kappa}B$ and AP-1 while its cytoplasmic domain deletion form, $L1{\Delta}CD$ did not suppressed their activities in RAW264.7 cells. Moreover, L1CAM suppressed nuclear translocation of p65 and p50 as well as c-Jun, c-Fos and p-ATF2 which are transcription factors of NF-${\kappa}B$ and AP-1, respectively. In conclusion, L1CAM suppressed inflammatory responses in macrophages through inhibiting NF-${\kappa}B$ and AP-1 pathways.

• Journal of The Korean Society of Integrative Medicine
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• v.7 no.4
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• pp.61-69
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• 2019

Purpose : Human gingival fibroblast cell is one of the the main cell types in periodontal tissue, which they can show anti-inflammatory activity through the production of numerous lines of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukins. Porphyromonas gingivalis, one of the oral pathogens, has reported to play a critical role in the development of periodontal diseases. This study aimed to investigate anti-inflammatory and antioxidative activities of Gracilaria textorii ethanol extract (GTEE) in P. gingivalis derived lipopolysaccharide (LPS-PG) stimulated human gingival fibroblast (HGF)-1 cell line. Methods : In order to analyze anti-inflammatory and antioxidative activities of GTEE in HGF-1 cell line, NOS enzyme activity, expression levels of iNOS, COX-2, NAD(P)H quinone dehydrogenase (NQO)1 and their transcription factors were estimated by Griess reaction and western hybridization. Results : LPS-PG induced overexpression of iNOS and COX-2, which was significantly attenuated by GTEE treatment in a dose-dependent manner without any cytotoxicity. In addition, intracellular NOS activity was in accordance with the result of iNOS expression. Due to important role in the regulation of inflammatory responses, phosphorylated status of p65 and c-jun, each subunit of nuclear factor (NF)-κB and activator protein (AP)-1, was also dose-dependently ameliorated by GTEE treatment. One of phase II enzymes, NQO1, and its transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), were analyzed since elevated phase II enzyme expression inhibited inflammatory response, which was significantly elevated by GTEE treatment in HGF-1 cell line. Conclusion : In conclusion, GTEE mitigated LPS-PG-stimulated inflammatory responses by attenuating NF-κB and AP-1 activation as well as accelerating NQO1 and Nrf2 expression in HGF-1 cell line. These results indicate that GTEE might be utilized a promising strategy for potential anti-inflammatory agent in periodontal diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.65-70
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• 2011

Osteoclasts play a critical role in bone-related diseases such as osteoporosis and rheumatoid arthritis by resorbing the bone. Recently, natural products from plants have been extensively studied as therapeutic drugs to treat and prevent various diseases. Here, we examined the effects of rhizoma arisaematis on ostoclast differentiation and bone resorption. We showed that rhizoma arisaematis significantly suppressed receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation in bone marrow-derived macrophages (BMMs) in a dose dependent manner but have little or no effect on the cytotoxicity of BMMs and RAW264.7 cells. We found that rhizoma arisaematis iarrow-ed the RANKL-induced c-Fos and nuclear factor of activated T cells (NFAT)c1, which is a master regulator of osteoclast differentiation. Furthermore, rhizoma arisaematis suppressed the mRNA expression of tartrate resistant-acid phosphatase and cathepsin K iaduced by RANKL in BMMs. in y chanistic studies, rhizoma arisaematis considerably iarrow-ed I-${\kappa}B$ degradation, which is a negative regulator of NF-${\kappa}B$, but iaduced the phosphderlation of p-38, ERK, and JNK.MMlso, we found that rhizoma arisaematis significantly iarrow-ed osteoclastic bone resorption. Taken tarether, our results suggest that rhizoma arisaematis suppresses osteoclast differentiation through down-regulatd the mRANKL-induced c-Fos and NFATc1 expression and iarrow-s bone resorption.