• Nutritional Sciences
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• v.9 no.2
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• pp.117-123
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• 2006

G. japonicum is a perennial hem and the flowering plant has been used as a diuretic and an astringent in Japan and China. However, little information is available about the anti-inflammatory action of G. japonicum. Therefore, the objective of this study was to investigate the antiinflammatory action of fractions from G. japonicum methanol extract. Inhibition of NO production was observed when cells were cotreated with fractions of G. japonicum and lipopolysaccharide. We observed that ethyl acetate fraction of G. japonicum inhibited NO production by LPS-activated RAW 264.7 cells, and that the suppression induced by ethyl acetate fraction of G. japonicum was associated with antioxidant activity and direct NO clearance. In addition, only ethyl acetate fraction of G. japonicum inhibited stimulated $PGE_2,\;TNF-\alpha,\;IL-1\beta$ production, whereas water and methyl chloride fractions showed no such effects. The ethyl acetate fraction of G. japonicum methanol extract showed a remarkable scavenging activity on the 1,1-diphenyl-2 picrylhydrazyl radical. Based on the results, ethyl acetate fraction of G. japonicum may be useful source as natural antioxidants and antiinflammation. Therefore, the results obtained from this study provide an alternative protective mechanism of ethyl acetate fraction of G. japonicum and provide information on the potential use of ethyl acetate fraction of G. japonicum in chemoprevention or pathogenic conditions related to overproduction of NO and $PGE_2$. However, the mechanism of the inflammatory effect must be evaluated through various parameters for induction of NO production.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.532-537
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• 2012

Avicularin, quercetin-3-${\alpha}$-L-arabinofuranoside, has been reported to possess diverse pharmacological properties such as anti-inflammatory and anti-infectious effects. However, the underlying mechanism by which avicularin exerts its anti-inflammatory activity has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of avicularin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Avicularin significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein levels of iNOS and COX-2, which are responsible for the production of NO and $PGE_2$, respectively. Avicularin also suppressed LPS-induced overproduction of pro-inflammatory cytokine IL-$1{\beta}$. Furthermore, avicularin significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-${\kappa}B$ in the nucleus. To understand the underlying signaling mechanism of anti-inflammatory activity of avicularin, involvement of multiple kinases was examined. Avicularin significantly attenuated LPS-induced activation of ERK signaling pathway in a concentration-dependent manner. Taken together, the present study clearly demonstrates that avicularin exhibits anti-inflammatory activity through the suppression of ERK signaling pathway in LPS-stimulated RAW 264.7 macrophage cells.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.2
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• pp.49-61
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• 2013

Objectives : This study was conducted to determine whether or not Kangwhaldoche-tang(Qianghuodaozhi-tang) (KDT) aqueous extracts can protect articular cartilage losses on the Freund's complete adjuvant(FCA)-induced rat rheumatoid arthritis. Methods : 520, 260 or 130 mg/kg of KDT were orally administered once a day for 14 days from 14 days after FCA treatments, and 15 mg/kg of dexamethasone was intraperitoneally administered as reference drug in this experiment. Changes on the body weight, knee circumferences, gross arthritis score, inflammatory tissue prostaglandin(PG) $E_2$ levels were monitored with cartilage collagen components and glucosaminoglycans(GAGs) compositions - chondroitin sulphate, heparin sulphate and hyaluronic acid in the present study. Results : As results of FCA treatment, classic rheumatoid arthritis featuring dramatic decreases of the body weights, cartilage collagen and GAGs contents with increases of the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels, were demonstrated in the present study. However, these changes from FCA - induced rheumatoid arthritis were clearly inhibited by treatment of dexamethasone and all three different dosages of KDT. Although overall anti-inflammatory effects of KDT 520 mg/kg were lowered than those of dexamethasone 15 mg/kg treated rats, KDT 520 mg/kg showed more favorable preserve effects on the cartilage GAGs and KDT 260 mg/kg treated rats showed similar preserve effects as compared with dexamethasone 15 mg/kg in this experiment. Conclusions : The present results supported that over 75 mg/kg of KDT showed favorable anti-arthritic effects on the FCA-induced arthritis mediated by suppression of $PGE_2$, representative inflammatory mediator, and may help improve rheumatoid arthritis.

• The Journal of Korean Medicine
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• v.30 no.1
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• pp.150-162
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• 2009

Objectives: Inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ playa critical role in inflammatory immune response. Therefore, intervention of inflammatory mediator production promises therapeutic benefit for treatment of many chronic inflammatory diseases, such as allergic asthma, rheumatoid arthritis, multiple sclerosis, septic shock and neurodegenerative diseases. In this study, the pharmacological effects of the flower MeOH extract Panax notoginseng (Notoginseng Flos; NF) on inflammation were investigated to address potential therapeutic or toxic effects. Methods: RA W264.7 cells were treated with different concentrations of NF methanol (NF-M) extract in the presence or absence of LPS ($1{\mu}g/m{\ell}$). Results: NF-M extract significantly inhibited LPS-induced production of NO, $PGE_2$ and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in a dose-dependent manner. In addition, NF-M extract suppressed mRNA expressions and protein levels of iNOS, COX-2 and pro-inflammatory cytokines in LPS-stimulated RA W264.7 cells. Conclusion: These results indicated that NF-M extract inhibits LPS-induced production of inflammatory mediators in macrophages and demonstrated that NF-M extract possesses anti-inflammatory properties in vitro.

• Journal of Haehwa Medicine
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• v.7 no.1
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• pp.939-955
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• 1998

Achyranthis Bidentatae Radix(ABR) is important prescriptions that have been used in oriental medicine for stomatitis and wound healing. The study was done to evaluate the inhibitory effects of cytotoxicity, formation of superoxide on the macrophage and neutrophil, prostaglandins($PGE_2$), interleukins($IL-1{\beta}$), collagenase activity and synthesis of collagen and DNA. The results were obtained as follows: 1. ABR was not showed the proliferation difference of human fibroblast and monocyte in 0.01% and 0.001% concentrations to be experimented and in result, it was concluded that they have no cytotoxicity but showed cytotoxicity in 0.1% concentrations. 2. ABR inhibited the formation of superoxide to 48% at the concentration of 0.001% in the mouse monocyte. 3. ABR inhibited the formation of superoxide to 40% at 0.001%, 58% at 0.0001% as compared with control in the human monocyte. 4. ABR inhibited the formation of superoxide to 58% at 0.0001%, 40% at 0.001% in the human neutrophil. 5. ABR was not showed the proliferation difference of human monocyte in all concentrations to be experimented and in result, it was concluded that they inhibited the formation of prostaglandins($PGE_2$) in the human monocyte stimulated with E. coli. 6. ABR showed the all concentration of inhibiting the production of inter1eukins($IL-1{\beta}$) in the human monocyte stimulated with E. coli. 7. ABR didn't influence on collagen synthesis and total protein in fibroblasts. 8. ABR inhibited the collagenase activity to 84% at 0.1%, 69% at 0.2%, 76% at 0.5%, 91% at 0.001% respectively.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.1
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• pp.47-78
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• 1999

Hoichunyonggyuksan(HCYGS) and Yongseksan(YSS) are important prescriptions that have been used in oriental medicine for stomatitis and wound healing. The study was done to evaluate the inhibitory effects of cytotoxicity, formation of superoxide on the macrophage and neutrophil, prostaglandins($PGE_2$), interleukins($IL-1{\Beta}$), collagenase activity and synthesis of collagen and DNA. The results were obtained as fo1lows: 1. HCYGS and YSS were not showed the proliferation difference of human fibroblast and monocyte in all concentrations to be experimented and in result, it was concluded that they have no cytotoxicity. 2. YSS inhibited the formation of superoxide to $48\% at the concentration of $0.001\%$ in the mouse monocyte. 3. HCYGS inhibited the formation of superoxide to $13\%$ at the concentration of $0.001\%$ as compared with control in the human monocyte. 4. HCYGS and YSS inhibited the formation of superoxide to $25\%\;and\;35\%$ respectively at the concentration of $0.0001\%\;and\;HCYGS\;showed\;38\%$ inhihitory rate on the formation of superoxide at concentration of $0.001\%$ in the human neutrophil. 5. The concentration of inhibiting the production of prostaglandins($PGE_2$) to $11\%$ in the human monocyte stimulated with E. coli were $0.01\%$ of HCYGS. 6. The concentration of inhibiting the production of interleukins($IL-l{\Beta}$) to $43\%\;and\;39\%$ in the human monocyte stimulated with E. coli were $0.01\%$ of HCYGS and YSS. 7. HCYGS and YSS didn't influence on collagen synthesis and total protein in fibroblasts. 8. HCYGS and YSS inhibited the collagenase activity to $22\%\;and\;19\%\;at\;0.1\%,\;45\%\;and\;56\%\;at\;0.2\%,\;57\%\;and\;52\%$ at $0.5\%$ respectively, but YSS exerted the inhibitory effect on collagenase activity to $27\%$ at the lower concentration of $0.01\%$. 9. HCYGS and YSS didn't show the faster recovary than control group hut exerted the consistant effect on the anti-inflammations and the formation of granulation tissue.

• Nutrition Research and Practice
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• v.11 no.4
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• pp.265-274
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• 2017

BACKGROUND/OBJECTIVES: Nelumbo leaves have been used in traditional medicine to treat bleeding, gastritis, hemorrhoids, and halitosis. However, their mechanisms have not been elucidated. MATERIALS/METHODS: The present study prepared two Nelumbo leaf extracts (NLEs) using water or 50% ethanol. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, and IL-6 and nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) productions were assessed. To determine the anti-inflammatory mechanism of NLEs, we measured nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity. Major metabolites of NLEs were also analyzed and quantified. RESULTS: NLEs effectively reduced the expression and productions of pro-inflammatory mediators such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, $PGE_2$, and NO. NLEs also reduced NF-${\kappa}B$ activity by inhibiting inhibitor of NF-${\kappa}B$ phosphorylation. Both extracts contained catechin and quercetin, bioactive compounds of NLEs. CONCLUSIONS: In this study, we showed that NLEs could be used to inhibit NF-${\kappa}B$-mediated inflammatory responses. In addition, our data support the idea that NLEs can ameliorate disease conditions involving chronic inflammation.

• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.5
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• pp.253-260
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• 2019

Background: Sometimes general anesthesia is required for dental surgery in pregnant women. Facial bone fractures or neck abscess should be treated immediately. Dental surgery, however, creates a stressful situation that can cause inflammation. Inflammatory responses are a well-known major cause of preterm labor and preterm birth. Here we demonstrate the effects of remifentanil on the factors related to preterm labor and its mechanism of action on amniotic-derived epithelial cells (WISH cells). Methods: WISH cells were exposed to lipopolysaccharide (LPS) for 24 h and co-treated with various concentrations of remifentanil. MTT assays were performed to measure cell viability. To explain the effects of remifentanil on the factors related to inflammation in WISH cells, activation of nuclear factor kappa B ($NF-{\kappa}B$) and p38 and the expression of interleukin $(IL)-1{\beta}$, tumor necrosis factor $(TNF)-{\alpha}$, cyclooxygenase (COX)2, and prostaglandin E $(PGE)_2$ were quantified using western blotting and RT-PCR, respectively. Results: Remifentanil did not affect WISH cell viability. In western blot analysis, co-treatment with remifentanil resulted in decreased phosphorylation of $NF-{\kappa}B$, and expression of COX2 and $PGE_2$ in LPS-induced inflammation, but the results were statistically significant only at low concentrations. Reduction of $IL-1{\beta}$ and $TNF-{\alpha}$ expression was also observed with RT-PCR. Conclusion: Co-treatment with remifentanil does not affect the viability of WISH cells, but reduces the expression of the factors related to inflammation, which can induce uterine contraction and preterm labor. These findings provide evidence that remifentanil may inhibit uterine contraction and preterm labor in clinical settings.

• Restorative Dentistry and Endodontics
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• v.44 no.2
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• pp.17.1-17.10
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• 2019

Objectives: Root resorption is an unexpected complication after replantation procedures. Combining anti-osteoclastic medicaments with retrograde root filling materials may avert this resorptive activity. The purpose of this study was to assess effects of a cathepsin K inhibitor with calcium silicate-based cements on osteoclastic activity. Methods: MC3T3-E1 cells were cultured for biocompatibility analyses. RAW 264.7 cells were cultured in the presence of the receptor activator of nuclear factor-kappa B and lipopolysaccharide, followed by treatment with Biodentine (BIOD) or ProRoot MTA with or without medicaments (Odanacatib [ODN], a cathepsin inhibitor and alendronate, a bisphosphonate). After drug treatment, the cell counting kit-8 assay and Alizarin red staining were performed to evaluate biocompatibility in MC3T3-E1 cells. Reverse-transcription polymerase chain reaction, tartrate-resistant acid phosphatase (TRAP) staining and enzyme-linked immunosorbent assays were performed in RAW 264.7 cells to determine the expression levels of inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and prostaglandin E2 (PGE2). Data were analyzed by one-way analysis of variance and Tukey's post hoc test (p < 0.05). Results: Biocompatibility results showed that there were no significant differences among any of the groups. RAW 264.7 cells treated with BIOD and ODN showed the lowest levels of $TNF-{\alpha}$ and PGE2. Treatments with BIOD + ODN were more potent suppressors of inflammatory cytokine expression (p < 0.05). Conclusion: The cathepsin K inhibitor with calcium silicate-based cement inhibits osteoclastic activity. This may have clinical application in preventing inflammatory root resorption in replanted teeth.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.395-401
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• 2021

Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E₂ (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.