• Title/Summary/Keyword: COX-1 activity

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Verification of Anti-Inflammatory Efficacy of Apple Mango (Mangifera indica L.) Peel in LPS-Activated Macrophage (LPS에 의해 활성화된 대식세포에서 애플망고 껍질(Mangifera indica L. Peel)의 항염증 효능 검증)

  • Hyo-Min Kim;Dan-Hee Yoo;In-Chul Lee
    • Microbiology and Biotechnology Letters
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    • v.50 no.3
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    • pp.337-346
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    • 2022
  • The purpose of this study was to investigate the antioxidant and anti-inflammatory activities of hot water (AMPW) and 70% ethanol (AMPE) extracts of apple mango (Mangifera indica L.) peel. The antioxidant activities were measured using a total polyphenol, electron-donating, 2,2'-azinobis [3-ethylbenzothiazoline6-sulfonic acid] (ABTS) radical scavenging assay. The total polyphenol content of AMPW and AMPE was 66.08 ± 0.62 mg TAE/100 g and 100.13 ± 0.23 mg TAE/100 g, respectively. As a result of measuring the electrondonating ability, at a concentration of 1,000 ㎍/ml, AMPW and AMPE showed an effectiveness of 86% and 94%, respectively. The ABTS assay showed 80% and 98% respective radical scavenging activity for AMPW and AMPE, at a concentration of 1,000 ㎍/ml. The cell viability on macrophage cells was performed using a 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay, and the results showed more than 90% cell viability at a 100 ㎍/ml concentration. Anti-inflammatory activity was verified by confirming nitric oxide (NO) production inhibitory activity, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) protein and mRNA expression inhibitory activity from lipopolysaccharide (LPS)-treated RAW 264.7 cells. The NO production inhibitory effects were measured using the Griess assay, which confirmed 45% and 40% inhibition after treatment with AMPW and AMPE, respectively. Moreover, the protein and mRNA expression of inflammatory-related factors iNOS and COX-2, decreased in a concentrationdependent manner. In conclusion, this study showed antioxidant and anti-inflammatory effects of Mangifera indica L. peel and revealed its promising potential for application as an antioxidant and anti-inflammatory agent.

Tribulus terrestris Suppresses the Lipopolysaccharide-Induced Inflammatory Reaction in RAW264.7 Macrophages through Heme Oxygenase-1 Expressions

  • Kim, Jai Eun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.1
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    • pp.63-68
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    • 2014
  • The fruit of Tribulus terrestris L. (Zygophyllaceae) is an important source of traditional Korean and Chinese medicines. In this study, NNMBS223, consisting of the ethanol extract of T. terrestris, showed potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS223 in suppressing the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and production of iNOS-derived nitric oxide (NO), COX-2-derived prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated macrophages. In addition, NNMBS223 induced expression of heme oxygenase (HO)-1 through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. The effects of NNMBS223 on LPS-induced production of NO and PGE2 were partially reversed by the HO activity inhibitor tin protoporphyrin (SnPP). These findings suggest that Nrf2-dependent increases in expression of HO-1 induced by NNMBS223 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

Anti-neuroinflammatory Effects of 12-Dehydrogingerdione in LPS-Activated Microglia through Inhibiting Akt/IKK/NF-κB Pathway and Activating Nrf-2/HO-1 Pathway

  • Zhao, Dong;Gu, Ming-Yao;Xu, Jiu Liang;Zhang, Li Jun;Ryu, Shi Yong;Yang, Hyun Ok
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.92-100
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    • 2019
  • Ginger, one of worldwide consumed dietary spice, is not only famous as food supplements, but also believed to exert a variety of remarkable pharmacological activity as herbal remedies. In this study, a ginger constituent, 12-dehydrogingerdione (DHGD) was proven that has comparable anti-inflammatory activity with positive control 6-shogaol in inhibiting LPS-induced interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, prostaglandin (PG) $E_2$, nitric oxide (NO), inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, without interfering with COX-1 in cultured microglial cells. Subsequent mechanistic studies indicate that 12-DHGD may inhibit neuro-inflammation through suppressing the LPS-activated $Akt/IKK/NF-{\kappa}B$ pathway. Furthermore, 12-DHGD markedly promoted the activation of NF-E2-related factor (Nrf)-2 and heme oxygenase (HO)-1, and we demonstrated that the involvement of HO-1 on the production of pro-inflammatory mediators such as NO and $TNF-{\alpha}$ by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting $Akt/IKK/I{\kappa}B/NF-{\kappa}B$ pathway and promoting Nrf-2/HO-1 pathway.

Inhibitory effects of thromboxane A2 generation by ginsenoside Ro due to attenuation of cytosolic phospholipase A2 phosphorylation and arachidonic acid release

  • Shin, Jung-Hae;Kwon, Hyuk-Woo;Rhee, Man Hee;Park, Hwa-Jin
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.236-241
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    • 2019
  • Background: Thromboxane A2 ($TXA_2$) induces platelet aggregation and promotes thrombus formation. Although ginsenoside Ro (G-Ro) from Panax ginseng is known to exhibit a $Ca^{2+}-antagonistic$ antiplatelet effect, whether it inhibits $Ca^{2+}-dependent$ cytosolic phospholipase $A_2$ ($cPLA_{2{\alpha}}$) activity to prevent the release of arachidonic acid (AA), a $TXA_2$ precursor, is unknown. In this study, we attempted to identify the mechanism underlying G-Ro-mediated $TXA_2$ inhibition. Methods: We investigated whether G-Ro attenuates $TXA_2$ production and its associated molecules, such as cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS), $cPLA_{2{\alpha}}$, mitogen-activated protein kinases, and AA. To assay COX-1 and TXAS, we used microsomal fraction of platelets. Results: G-Ro reduced $TXA_2$ production by inhibiting AA release. It acted by decreasing the phosphorylation of $cPLA_{2{\alpha}}$, p38-mitogen-activated protein kinase, and c-Jun N-terminal kinase1, rather than by inhibiting COX-1 and TXAS in thrombin-activated human platelets. Conclusion: G-Ro inhibits AA release to attenuate $TXA_2$ production, which may counteract $TXA_2-associated$ thrombosis.

Anti-inflammation Activities of Cultured Products from Suspension Culture of Aloe vera Callus (Aloe vera Callus 현탁배양 생성물의 항염증 활성)

  • Kim, Myung Uk;Cho, Young Je;Lee, Shin Young
    • Journal of Applied Biological Chemistry
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    • v.56 no.3
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    • pp.157-163
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    • 2013
  • Cultured products (callus and exopolysaccharide) were obtained from suspension culture of Aloe vera callus, and the extracts of callus were further prepared with cold water or 60% ethanol solution. The ethanol extract of callus (AC) and exopolysaccharide (ACP) of 10 mg/mL exhibited the relatively higher suppression activity of 43.2-52.1% against hyaluronidase activity. Thus, their anti-inflammatory effects were further investigated using animal cell (Raw 264.7) in vitro. Though AC shows a slight suppression effect of cell survival rate (97%) using MTT assay in the presence of $400{\mu}g/mL$ AC- dimethyl sulfoxide (DMSO), cell growth promotion was observed in the other samples of lower levels. It indicates that the ethanol extract of Aloe callus rarely affect cell survival rate in the ranges ($200-400{\mu}g/mL$) used in the study. Using Griess reagent, the suppression of NO production by the aloe callus extract was analyzed by measuring the amount of the nitrite produced in Raw 264.7 culture activated by lipopolysaccharide (LPS). As a result, supplementation of AC-distilled water (DW) and AC-DMSO produced higher levels of NO than the positive control LPS. However, the NO suppression effect by ACP-DW was so intense that lower amount ($80-100{\mu}g/mL$) suppressed NO production to the level of the control. The effect was attributed to the expression of the iNOS. Then, Raw 264.7 cells were stimulated with the LPS and expression of COX-2 protein level was analyzed depending on the Aloe suspension culture product treatment. The results showed that the ACP-DW supplemented medium did not express COX-2 by itself, and LPS stimulated COX-2 expression was slightly decreased. On the other hand, realtime-PCR analysis of the expression of inflammatory cytokine showed that IL-$1{\beta}$ and TNF-${\alpha}$ expression was highly suppressed in the ACP- distilled water supplemented medium.

Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-κB in LPS-stimulated RAW264.7 cells and mouse liver

  • Kim, Dae Hyun;Chung, Jae Heun;Yoon, Ji Sung;Ha, Young Mi;Bae, Sungjin;Lee, Eun Kyeong;Jung, Kyung Jin;Kim, Min Sun;Kim, You Jung;Kim, Mi Kyung;Chung, Hae Young
    • Journal of Ginseng Research
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    • v.37 no.1
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    • pp.54-63
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    • 2013
  • Ginsenoside Rd is a primary constituent of the ginseng rhizome and has been shown to participate in the regulation of diabetes and in tumor formation. Reports also show that ginsenoside Rd exerts anti-oxidative effects by activating anti-oxidant enzymes. Treatment with ginsenoside Rd decreased nitric oxide and prostaglandin $E_2$ ($PGE_2$) in lipopolysaccharides (LPS)-challenged RAW264.7 cells and in ICR mouse livers (5 mg/kg LPS; LPS + ginsenoside Rd [2, 10, and 50 mg/kg]). Furthermore, these decreases were associated with the down-regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 and of nuclear factor (NF)-${\kappa}B$ activity in vitro and in vivo. Our results indicate that ginsenoside Rd treatment decreases; 1) nitric oxide production (40% inhibition); 2) $PGE_2$ synthesis (69% to 93% inhibition); 3) NF-${\kappa}B$ activity; and 4) the NF-${\kappa}B$-regulated expressions of iNOS and COX-2. Taken together, our results suggest that the anti-inflammatory effects of ginsenoside Rd are due to the down-regulation of NF-${\kappa}B$ and the consequent expressional suppressions of iNOS and COX-2.

Anti-inflammatory Effects of Ethanolic Extracts from Codium fragile on LPS-Stimulated RAW 264.7 Macrophages via Nuclear Factor kappaB Inactivation

  • Yoon, Ho-Dong;Jeong, Eun-Ji;Choi, Ji-Woong;Lee, Min-Sup;Park, Myoung-Ae;Yoon, Na-Young;Kim, Yeon-Kye;Cho, Deuk-Moon;Kim, Jae-Il;Kim, Hyeung-Rak
    • Fisheries and Aquatic Sciences
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    • v.14 no.4
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    • pp.267-274
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    • 2011
  • Bacterial lipopolysaccharide (LPS) induces expression of pro-inflammatory cytokines and enzymes producing nitric oxide (NO) and prostaglandins (PGs) in immune cells. This process is mediated by the activation of nuclear factor kappaB (NF-${\kappa}B$). In this study, we investigated the anti-inflammatory characteristics of Codium fragile ethanolic extract (CFE) mediated by the regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using LPS-stimulated murine macrophage RAW 264.7 cells. CFE significantly inhibited LPS-induced NO and $PGE_2$ production in a dose-dependent manner and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells with no cytotoxicity. Pro-inflammatory cytokines, such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$, were significantly reduced by treatment of CFE in LPS-stimulated RAW 264.7 cells. CFE inhibited the promoter activity of (NF)-${\kappa}B$ in LPS-stimulated macrophages. Treatment with CFE suppressed translocation of the NF-${\kappa}B$ p65 subunit by preventing proteolytic degradation of inhibitor of ${\kappa}B-{\alpha}$. These results indicate that the CFE-mediated inhibition of NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells is mediated through the NF-${\kappa}B$-dependent transcriptional downregulation of iNOS and COX-2, suggesting the potential of CFE as a nutraceutical with anti-inflammatory activity.

Effects of FLOS LONICERAE Water Extract On Anti-Rheumatiod Arthritis (금은화(金銀花)의 항(抗)류마티즘 효능(效能)에 대한 연구(硏究))

  • Kim, Hee-Soo;Ki, Ho-Pil;Lee, Joon-Suh;Yun, Yong-Gab
    • Herbal Formula Science
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    • v.18 no.2
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    • pp.183-199
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    • 2010
  • Rheumatoid arthritis is characterized by the focal loss of cartilage due to an up-regulation of inflammatory pathways, which produce inflammatory mediators, such as interleukin-1beta(IL-$1{\beta}$), IL-6, tumour necrosis factor alpha(TNF-$\alpha$), prostaglandin, and nitric oxide(NO). We investigated the anti-arthritic effects of water extract from FLOS LONICERAE(FLWE) in vitro and in vivo. Extract inhibited the production of inflammatory mediators(NO, IL-$1{\beta}$, TNF-$\alpha$, and prostaglandin $E_2$) and the expression of inducible NO synthase(iNOS) and cyclooxygenase-2(COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a dose-dependent manner. FLWE also inhibited TNF-$\alpha$, IL-$1{\beta}$, IL-6, and $PGE_2$ production as well as COX activity in collagen-induced mouse arthritis. Moreover, FLWE significantly suppressed collagen-induced mouse arthritis. These results suggest that FLOS LONICERAE may be useful for therapy against inflammatory immune diseases and rheumatoid arthritis, probably by suppressing the production of inflammatory mediators.

Evaluation of Antioxidant and Anti-Inflammatory Activities of Ascidian Tunic Carotenoids As a Source of Color Cosmetics (멍게껍질 카로테노이드의 색조 화장품 원료의 항산화, 항염증 기능성 평가)

  • Ticar, Bernadeth;Rohmah, Zuliyati;Bat-Erdene, Munkhjagal;Park, Si-Hyang;Choi, Byeong-Dae
    • KSBB Journal
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    • v.28 no.1
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    • pp.36-41
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    • 2013
  • Carotenoids are fat-soluble red-orange colored pigments found in plants and seafood-derived products, including algae, seaweeds, and fish muscle. In this study, we have demonstrated the molecular mechanism underlying the antioxidants and anti-inflammatory properties of ascidian tunic carotenoids using mouse macrophage cell line (RAW 264.7). Cell viability was not affected by treatment of carotenoids < 10 ${\mu}g/mL$. This treatment also showed negative inhibition on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) and cyclooxygenase-2 (COX-2). The DPPH radical scavenging activity of carotenoids was 47.2% at 100 mg/mL. It also has a potential reducing power (1.025) comparable with ascorbic acid (1.584). The ascidian tunic carotenoids would make a candidate for the commercially interesting biologically active cosmetic pigments.

Effects of Butanol extract from Rhois Vernicifluae Cortex (RVC) in lipopolysaccharides-induced macrophage RAW 264.7 cells (칠피(漆皮) 부탄올 분획물이 LPS로 유도된 RAW 264.7 대식세포에 미치는 영향)

  • Song, Saeng-Yeop;Sim, Sung-Yong;Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.20 no.1 s.32
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    • pp.1-15
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    • 2007
  • Objectives : RVC has long been used for a useful natural agent ameliorating inflammation related symptoms in the folk medicine recipe. This study was performed to investigate effects of RVC on the inflammation and oxidation in RAW 264.7 cells. Methods : The RVC was extracted with 80% ethanol and sequentially partitioned with solvents in order to increase polarity. With the various fractions, we determined the activities on the inflammation and oxidation in RAW 264.7 cells. Results : 1. Among the various solvent extracts of RVC, the butanol fraction showed the most powerful inhibitory ability against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells without affecting cell viability. 2. Butanol fraction showed a oxidation inhibition effect by decreasing the DPPH and OH radicals. 3. Butanol fraction exhibited the inhibitory avilities against iNOS and COX-2. 4. Reverse transcriptase polymerase chain reaction (RT-PCR) and Westem blotting analysis revealed that the BuOH fraction provided a primary inhibitor of the iNOS protein and mRNA expression in LPS-induced RAW 264.7 cells. Among the up-regulater molecules of iNOS and COX-2, the BuOh fraction of RVC was shown the inhibitory activity of phoshporylation of c-Jun N-terminal kinase (JNK) 1/2 and threonine protein kinase (AKT), the one of the MAPKs pathway. Conclusion : Thus, the present study suggests that the response of a component of the BuOH fraction to NO generation via iNOS expression provide a important clue to elucidate anti-inflammatory and anti-oxidation mechanism of RVC.

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