• Title/Summary/Keyword: COX-2 inhibition

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Anti-Oxidative and Anti-Inflammatory Effects of the Solvent Fraction from Theobroma cacao L. Extract (카카오(Theobroma cacao L.) 용매 분획물의 항산화 및 항염증 효과)

  • Kim, Young-Sun;Lee, Jin-Young;Cho, Young-Je;An, Bong-Jeun
    • Journal of Life Science
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    • v.22 no.10
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    • pp.1330-1338
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    • 2012
  • Solvent extracts of Theobroma cacao L. (TCL) were investigated for anti-oxidative and anti-inflammatory effects in order to consider TCL as a functional ingredient for cosmetic products. TCL(A) extract was fractioned according to polarity with $CHCl_3$, EtOAc, n-BuOH, and water. Following TCL(A) fractionation, the electron-donating ability of the n-BuOH and EtOAc solvent fractions (each 100 ${\mu}g/ml$) was about 76.2% and 53.9%, respectively. The superoxide anion radical inhibitory effect of the n-BuOH and EtOAc solvent fractions (each 50 ${\mu}g/ml$) was about 76.09% and 51.4%, respectively. Results of lipid oxidation showed that $Fe^{2+}$ had a greater chelating effect than $Cu^{2+}$. The $Fe^{2+}$ chelating effect of the EtOAc solvent fraction (50 ${\mu}g/ml$) was about 64%. Hyaluronidase inhibition related to the anti-inflammatory effect was 53.0% with EtOAc at 100 ${\mu}g/ml$, while the lipoxygenase inhibitory effect was about 51.32% at 10 ${\mu}g/ml$. The anti-inflammatory activity in the EtOAc fraction inhibited the generation of nitric oxide. Results also showed that iNOS protein expression increased in RAW264.7 cells. In contrast, at 100 ${\mu}g/ml$ EtOAc, iNOS and COX-2 protein expression significantly decreased in LPS-stimulated RAW 264.7 cells.

Antioxidant and anti-inflammatory effects and mechanism of Abeliophyllum distichum leaf extract in RAW264.7 macrophages (RAW264.7 대식세포에서 미선나무 잎 추출물의 항산화, 항염증 효능 및 기전연구)

  • Juhee Yoo;Kyung-Ah Kim
    • Journal of Nutrition and Health
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    • v.56 no.5
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    • pp.455-468
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    • 2023
  • Purpose: Abeliophyllum distichum (A.distichum) is a plant native to Korea. In this study, we investigated the mechanism of antioxidant and anti-inflammatory effects of the leaf extract of A.distichum. Methods: The antioxidant capacity of the A.distichum leaf extract was determined based on the total polyphenol content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and the ferric reducing antioxidant power (FRAP) assay. The anti-inflammatory effects of the A.distichum leaf extract were evaluated by measuring the production of nitric oxide (NO) and the expression levels of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 using the enzyme-linked immunosorbent assay (ELISA) and reverse transcription quantitative real-time PCR (RT-qPCR). In addition, the expression of heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid 2 related factor (Nrf2), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2), as well as the activation of nuclear factorkappa B (NF-ĸB) were examined using the western blot analysis. Results: The total polyphenol content of the A.distichum leaf extract was 329.89 ± 30.17 gallic acid equivalents mg/g and the DPPH and ABTS scavenging activities were 55% and 70%, respectively. Additionally, the FRAP value of the extract was 743.68 ± 116.59 mg/mL. After 12-hour treatment with the A.distichum leaf extract, there was a tendency for the Nrf2 expression to increase, and the expression of HO-1 was significantly elevated in the RAW264.7 cells. The A.distichum leaf extract treatment resulted in decreased levels of NO, TNF-α, IL-6, and IL-1β, as well as reduced expression of iNOS and COX-2, along with inhibition of NF-κB activation in lipopolysaccharide-stimulated RAW264.7 cells. Conclusion: These results suggest that the A.distichum leaf extract exerts antioxidative and anti-inflammatory effects by upregulating the expression of HO-1 and downregulating NF-κB activation.

Saucerneol F, a New Lignan Isolated from Saururus chinensis, Attenuates Degranulation via Phospholipase Cγ1 Inhibition and Eicosanoid Generation by Suppressing MAP Kinases in Mast Cells

  • Lu, Yue;Son, Jong-Keun;Chang, Hyeun Wook
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.526-531
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    • 2012
  • During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$), cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$), and on phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid ($PGD_2$ and $LTC_4$) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of $PLC{\gamma}1$, intracellular $Ca^{2+}$ influx, the translocation of cytosolic phospholipase $A_2$ ($cPLA_2$) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular $Ca^{2+}$ influx by inhibiting $PLC{\gamma}1$ phosphorylation and suppressing the nuclear translocations of $cPLA_2$ and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

Fagopyrum esculentum Extract Suppresses the Release of Inflammatory Mediator and Proximal Signal Events in $Fc{\varepsilon}RI$-mediated RBL-2H3 Cell Activation (교맥(蕎麥)의 비만세포 염증매개물질의 분비와 $Fc{\varepsilon}RI$ 신호전달에 미치는 효과)

  • Kang, Kyung-Hwa
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.4
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    • pp.469-474
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    • 2012
  • Fagopyrum esculentum(FE) is an important food crop and medicinal plant that is used to improve diabetes, obesity, hypertension, hypercholesterolemia and constipation in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. We investigated the effects on the release of inflammatory mediator and proximal signal events in $Fc{\varepsilon}RI$-mediated RBL-2H3 cell activation. FE reduced antigen (DNP-HSA)-induced release of histamine, prostaglandin D2 (PGD2) and cysteinyl Leukotriene (cysLT) in IgE-sensitized RBL-2H3 cells. In addition, it inhibited antigen-induced HDC2 and COX-2 and 5-LO mRNA expression in IgE-sensitized RBL-2H3 cells. FE also suppressed antigen-induced $Fc{\varepsilon}RI{\beta}$ and $Fc{\varepsilon}RI{\gamma}$ subunit mRNA expression in these cells. To identify the mechanisms underpinning the inhibition of release of inflammatory mediators such as histamine and PGD2 and cysLT by FE, we examined the proximal signal events of intracellular FceRI signaling molecules. FE suppressed antigen-induced phosphorylation of Lyn, Syk, LAT, $PLC{\gamma}1$, PI3K, Akt and cPLA2. Collectively, the anti-allergic effects of FE in vitro suggest its possible therapeutic application to inflammatory allergic diseases, in which its inhibition of inflammatory mediator and FceRI-dependent signaling events in mast cells may be hugely beneficial.

Effect of Hwao-tang on Superoxide Generation and Neutrophil Functions

  • Park Soo Young;Kim Han Geu;Lee Soo Kyung;Ahan Jong Chan;Chung Tae Wook;Moon Jin-Young;Park Sun Dong;Kim June Ki;Choi Dall Yeong;Kim Cherl Ho;Park Won Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.230-240
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    • 2003
  • We investigated that Hwao-tang had various effects on stimulus-induced superoxide generation in human neutrophils. Hwao-tang significantly inhibited N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation in a concentration-dependent manner, but not that induced by arachidonic acid. Also, Hwao-tang significantly reduced mouse paw oedema induced by carrageenan. The results suggest that protein tyrosine kinase participates in fMLP-mediated superoxide generation by Hwao-tang-treated human neutrophils. Also, the results indicate that Hwao-tang exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E2 production, which could be due to a decreased expression of iNOS and COX-2.

In Vitro Inhibition of Pro-inflammatory Mediator mRNA Expression by Nephrite in Lipopolysaccharide-induced Mouse Macrophage Cells (RAW 264.7 면역세포에서 염증유발인자의 유전자 발현에 대한 연옥수와 연옥분의 억제효과)

  • Yeom Mi-jung;Choi Bo-Hee;Han Dong-Oh;Lee Hye-Jung;Shim Insop;Kim Sung-Hoon;Hahm Dae-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1622-1627
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    • 2004
  • Nephrite has been widely used as a medicinal mineral resource to treat a numerous chronic diseases and to replenish vital essence and blood in the Korean traditional medicine. However, as of yet, there is little understanding of the pharmacological and biochemical mechanisms of its therapeutic effects as regards anti-inflammation. We therefore examined whether nephrite represses the expression of major inflammation mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), in LPS-stimulated murine macrophage cell line, RAW264.7 by using RT-PCR. The powder suspension and water extracts of nephrite significantly inhibited the mRNA expression of the mediators, despite a little toxic effects on growth of RAW 264.7 cells within the concentration range tested. These experimental results suggested that the nephrite can be utilized as a functional mineral exerting the anti-inflammation medicinal effect.

Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3

  • Lee, Do Yeon;Hwang, Chul Ju;Choi, Ji Yeon;Park, Mi Hee;Song, Min Ji;Oh, Ki Wan;Son, Dong Ju;Lee, Seung Hwa;Han, Sang Bae;Hong, Jin Tae
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.535-544
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    • 2017
  • Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264.7 cells. Pull down assay and docking model analysis showed that carnosol directly binds to the DNA binding domain (DBD) of STAT3. We next examined the anti-atopic activity of carnosol ($0.05{\mu}g/cm^2$) using 5% Phthalic anhydride (PA)-induced AD model in HR1 mice. Carnosol treatment significantly reduced 5% PA-induced AD like skin inflammation in skin tissues compared with control mice. Moreover, carnosol treatment inhibits the expression of iNOS and COX-2 in skin tissue. In addition, the levels of $TNF-{\alpha}$, $IL-1{\beta}$, and Immunoglobulin-E in blood serum was significantly decreased in carnosol treated mice compared with those of 5% PA treated group. Furthermore, the activation of STAT3 in skin tissue was decreased in carnosol treated mice compared with control mice. In conclusion, these findings suggest that carnosol exhibited a potential anti-AD activity by inhibiting pro-inflammatory mediators through suppression of STAT3 activation via direct binding to DBD of STAT3.

Phosphorylation of Akt Mediates Anti-Inflammatory Activity of 1-p-Coumaroyl ${\beta}$-D-Glucoside Against Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells

  • Vo, Van Anh;Lee, Jae-Won;Kim, Ji-Young;Park, Jun-Ho;Lee, Hee Jae;Kim, Sung-Soo;Kwon, Yong-Soo;Chun, Wanjoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.1
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    • pp.79-86
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    • 2014
  • Hydroxycinnamic acids have been reported to possess numerous pharmacological activities such as antioxidant, anti-inflammatory, and anti-tumor properties. However, the biological activity of 1-p-coumaroyl ${\beta}$-D-glucoside (CG), a glucose ester derivative of p-coumaric acid, has not been clearly examined. The objective of this study is to elucidate the anti-inflammatory action of CG in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-$1{\beta}$ and TNF-${\alpha}$. In addition, CG significantly suppressed LPS-induced degradation of $I{\kappa}B$. To elucidate the underlying mechanism by which CG exerts its anti-inflammatory action, involvement of various signaling pathways were examined. CG exhibited significantly increased Akt phosphorylation in a concentration-dependent manner, although MAPKs such as Erk, JNK, and p38 appeared not to be involved. Furthermore, inhibition of Akt/PI3K signaling pathway with wortmannin significantly, albeit not completely, abolished CG-induced Akt phosphorylation and anti-inflammatory actions. Taken together, the present study demonstrates that Akt signaling pathway might play a major role in CG-mediated anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells.

Anti-Inflammatory Effect of Fermented Doenjang Containing a Halophytes Suaeda asparagoides (Miq.) Powder on RAW 264.7 Cells (대식세포에서 나문재 분말을 함유한 된장의 항염증 효과)

  • Gil, Na-Young;Choi, Bo-Young;Yeo, Soo-Hwan;Kim, So-Young
    • The Korean Journal of Food And Nutrition
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    • v.32 no.6
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    • pp.651-661
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    • 2019
  • Suaeda asparagoides (Miq.) is a salt marsh plant, long been prescribed in traditional medicine for the treatment of hypertension and liver toxification in Asian countries. The powder of S. asparagoides was added at the ratio of 0, 5, and 10%, respectively, of grain-type Meju to manufacture Doenjang in brine according to the salt concentration (8 and 12%). After 24 weeks of fermentation, the Doenjang samples were determined to have an anti-inflammatory effect on RAW 264.7 cells. Evaluation of the anti-inflammatory effect of Doenjang added S. asparagoides powder extracted using 80% EtOH, was performed to study the inhibition of pro-inflammatory factors such as NF-κB (nuclar factor κB), NO (nitric oxide), TNF-α (tumor necrosis factor alpha), IL-6 (interleukin-6), iNOS (inducible nitric oxide synthase), and COX-2 (cyclooxygenase-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. The results showed that the Doenjang extracts reduced the production of NO, IL-6, COX-2, and iNOS increased in the LPS-stimulated RAW cell without cytotoxicity. In the case of the NF-κB and TNF-α there was no significant difference between the control and samples. In conclusion, these results suggest that Doenjang added with the S. asparagoides powder acts as functional fermented food with anti-inflammation effect.

Anti-Inflammatory Mode of Isoflavone Glycoside Sophoricoside by Inhibition of Interleukin-6 and Cyclooxygenase-2 in Inflammatory Response

  • Kim, Byung-Hak;Chung, Eun-Yong;Ryu, Jae-Chun;Jung, Sang-Hun;Min, Kyung-Rak;Kim, Youngsoo
    • Archives of Pharmacal Research
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    • v.26 no.4
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    • pp.306-311
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    • 2003
  • Soy, high dietary intake for the oriental population, is a main source of isoflavonoids. Sophoricoside (SOP) an isoflavone glycoside was isolated from immature fruits of Sophora japonica (Leguminosae family) and its inhibitory effect on chemical mediators involved in inflammatory response was investigated in this study. SOP inhibited the interleukin (IL)-6 bioactivity with an $IC_{50}$ value of 6.1 $\mu$M whereas it had no effects on IL-1$\beta$ and TNF-a bioactivities. SOP was identified as a selective inhibitor of cyclooxygenase (COX)-2 activity with an $IC_{50}$ value of 4.4 $\mu$ M, but did not show inhibitory effect on the synthesis of COX-2. However, SOP had no effect on the production of reactive oxygen species including superoxide anions and nitric oxide. These results revealed that in vitro anti-inflammatory action of SOP is significantly different from that of genistein known as a phytoestrogen of soy products. This experimental study has documented an importance of dietary soy isoflavonoids as multifunctional agents beneficial to human health, and will help to clarify protective mechanisms of SOP against inflammatory conditions.