• Title/Summary/Keyword: Prostaglandin E2 Tumor necrosis factor-$\alpha$

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Anti-Inflammatory Effect of Licochalcone E, a Constituent of Licorice, on Lipopolysaccharide-Induced Inflammatory Responses in Murine Macrophages (Licochalcone E의 항염증 효과와 그 기전에 대한 연구)

  • Park, Geun-Mook;Jun, Jong-Gab;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.21 no.5
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    • pp.656-663
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    • 2011
  • Licochalcone, a major phenolic constituent of the licorice species Glycyrrhiza inflata, a constituent of licorice, exhibits various biological properties, including chemopreventive-, antibacterial-, and anti-spasmodic activities. Recently, Licochalcone E (LicE) was isolated from the roots of Glycyrrhiza inflate, however its biological functions have not been fully examined. In the present study, we investigated the ability of LicE to regulate inflammation reactions in macrophages. Our in vitro experiments using murine macrophages, RAW264.7 cells, showed that LicE suppressed not only nitric oxide (NO) and prostaglandin $E_2$ generation, but also the expression of inducible NO synthase and cyclooxygenase-2 induced by lipopolysaccharide (LPS). Similarly, LicE inhibited the release of proinflammatory cytokines induced by LPS in RAW264.7 cells, including tumor necrosis factor-${\alpha}$ and interleukin-6. The underlying mechanism of LicE on anti-inflammatory action correlated with down-regulation of the nuclear factor-${\kappa}$B. Our data collectively indicate that LicE inhibited the production of several inflammatory mediators and might be used in the treatment of various inflammatory diseases.

Bojungikgitang Inhibits LPS Plus $Interferon-{\gamma}-induced$ Inflammatory Mediators in RAW 264.7 Macrophages (보중익기탕(補中益氣湯)의 Lipopolysaccharide와 $Interferon-{\gamma}$에 의해 유도되는 염증성 매개물에 대한 억제 효과(效果))

  • Jang Seon-Il;Kim Hyung-Jin;Kim Young-Jun;Pae Hyun-Ock;Chung Hun-Taeg;Yun Yong-Gab;Jeong Ok-Sam;Kim Youn-Chul
    • Herbal Formula Science
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    • v.11 no.1
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    • pp.115-128
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    • 2003
  • Bojungikgitang is the water extracts prepared from Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Astractylodis Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Bupleuri Radix, Cimicifugae Rhizoma, which has been used for the treatment of indigestion, and immunological disease in oriental countries. In this study, the effects of Bojungikgitang on the productions of nitiric oxide (NO) and prostaglandin $E_2\;(PGE_2)$, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using RAW 264.7 macrophages activated with $interferon-{\gamma}\;(IFN-{\gamma})$ plus lipopolysaccharide (LPS). Bojungikgitang (10-400 ${\mu}$g/ml) per se had no cytotoxic effect in unstimulated macrophages, but this compound dose-dependently reduced the release of NO and $PGE_2$ caused by stimulation of $LPS/IFN-{\gamma}$. The levels of iNOS and COX-2 protein were markedly suppressed by the treatment with Bojungikgitang in a concentration dependent manner. Moreover, Bojungikgitang also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (1L)-1${\beta}$ and IL-6 in LPS-stimulated RAW 264.7 macrophages. These results suggest that Bojungikgitang decreases the NO and $PGE_2$ production in macrophages by inhibiting iNOS and COX-2 expression and these properties may contribute to the anti-inflammatory activity of Bojungikgitang.

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Molecular mechanism of protopanaxadiol saponin fraction-mediated anti-inflammatory actions

  • Yang, Yanyan;Lee, Jongsung;Rhee, Man Hee;Yu, Tao;Baek, Kwang-Soo;Sung, Nak Yoon;Kim, Yong;Yoon, Keejung;Kim, Ji Hye;Kwak, Yi-Seong;Hong, Sungyoul;Kim, Jong-Hoon;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.61-68
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    • 2015
  • Background: Korean Red Ginseng (KRG) is a representative traditional herbal medicine with many different pharmacological properties including anticancer, anti-atherosclerosis, anti-diabetes, and anti-inflammatory activities. Only a few studies have explored the molecular mechanism of KRG-mediated anti-inflammatory activity. Methods: We investigated the anti-inflammatory mechanisms of the protopanaxadiol saponin fraction (PPD-SF) of KRG using in vitro and in vivo inflammatory models. Results: PPD-SF dose-dependently diminished the release of inflammatory mediators [nitric oxide (NO), tumor necrosis factor-${\alpha}$, and prostaglandin $E_2$], and downregulated the mRNA expression of their corresponding genes (inducible NO synthase, tumor necrosis factor-${\alpha}$, and cyclooxygenase-2), without altering cell viability. The PPD-SF-mediated suppression of these events appeared to be regulated by a blockade of p38, c-Jun N-terminal kinase (JNK), and TANK (TRAF family member-associated NF-kappa-B activator)-binding kinase 1 (TBK1), which are linked to the activation of activating transcription factor 2 (ATF2) and interferon regulatory transcription factor 3 (IRF3). Moreover, this fraction also ameliorated HCl/ethanol/-induced gastritis via suppression of phospho-JNK2 levels. Conclusion: These results strongly suggest that the anti-inflammatory action of PPD-SF could be mediated by a reduction in the activation of p38-, JNK2-, and TANK-binding-kinase-1-linked pathways and their corresponding transcription factors (ATF2 and IRF3).

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 Lycopene on the Expression of Pro-inflammatory Genes in Human Vascular Endothelial Cells (혈관내피세포에서 라이코펜이 염증유전자 발현에 미치는 영향)

  • Kim, Tae-Hoon;Bae, Jong-Sup
    • Food Science and Preservation
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    • v.19 no.2
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    • pp.287-293
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    • 2012
  • Lycopene, found in tomatoes and tomato products, has antioxidant, anticancer, and anti-inflammatory effects. High-mobility-group box 1 (HMGB1) mediates the pro-inflammatory responses in several inflammatory diseases. In this study, the potential roles of lycopene in the HMGB1-mediated pro-inflammatory gene expressions in the primary human-umbilical-vein endothelial cells (HUVECs) were investigated. The data showed that HMGB1 upregulated the expressions of monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6), secretory phospholipase A2 (sPLA2)-IIA, and prostaglandin E2 (PGE2). Lycopene pre-incubation for 6 h decreased the HMGB1-mediated induction of MCP-1, IL-6, sPLA2-IIA, and PGE2. Further study revealed that the inhibitory effects of lycopene on the HMGB-1 induced expression of pro-inflammatory genes were mediated by the inhibition of two important inflammatory cytokines: tumor necrosis factor (TNF)-${\alpha}$ and nuclear factor (NF)-${\kappa}B$. These results suggest that HMGB1 upregulated the expression of pro-inflammatory genes and lycopene inhibited HMGB-1-induced pro-inflammatory genes by inhibiting TNF-${\alpha}$ and NF-${\kappa}B$. This finding will serve as an important evidence in the development of a new medicine for the treatment of inflammatory diseases.

Zanthoxylum rhetsa Stem Bark Extract Inhibits LPS-induced COX-2 and iNOS expression in RAW 264.7 Cells via the NF-${\kappa}B$ Inactivation

  • Thu, Nguyen Bich;Trung, Trinh Nam;Ha, Do Thi;Khoi, Nguyen Minh;Than, Nguyen Viet;Soulinho, Thipthaviphone;Nam, Nguyen Hai;Phuong, Tran Thi;Bae, Ki-Hwan
    • Natural Product Sciences
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    • v.16 no.4
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    • pp.265-270
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    • 2010
  • The methanol extract of Zanthoxylum rhetsa (MZRR) were evaluated for its ability to suppress the formation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. MZRR presented an inhibition of LPS-induced production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that MZRR significantly inhibited the protein and mRNA expressions of iNOS and COX-2 in LPS-activated macrophages in a dose-dependent manner. LPS-induced COX-2, iNOS, and nuclear factor kappa beta (NF-${\kappa}B$) activity were also decreased in the presence of MZRR. The production of tumor necrosis factor-$\alpha$ (TNF-$\alpha$), the mRNA expression levels of pro-inflammatory cytokines, including TNF-$\alpha$ and IL-$1{\beta}$, were reduced after MZRR administration in a dose dependent-manner. These results suggest that the MZRR extract involved in the inhibition of iNOS and COX-2 via the NF-${\kappa}B$ pathway, revealing a partial molecular basis for anti-inflammatory properties of the MZRR extract.

Ethanolic Extract of Chondria crassicaulis Inhibits the Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in LPS-Stimulated RAW 264.7 Macrophages

  • Kim, Yeon-Kye;Jeong, Eun-Ji;Lee, Min-Sup;Yoon, Na-Young;Yoon, Ho-Dong;Kim, Jae-Il;Kim, Hyeung-Rak
    • Fisheries and Aquatic Sciences
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    • v.14 no.4
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    • pp.275-282
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    • 2011
  • Inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been implicated in various inflammatory diseases. In this study, we investigated the anti-inflammatory activities of Chondria crassicaulis ethanolic extract (CCE) by measuring its effects on the expression of iNOS and COX-2 proteins in lipopolysaccharide (LPS)-treated RAW 264.7 murine macrophages. CCE significantly and dose-dependently inhibited the LPS-induced release of nitric oxide and prostaglandin $E_2$, and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells, without causing any cytotoxicity. It also inhibited the production of the pro-inflammatory cytokines such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$ in LPS-stimulated RAW 264.7 cells. Moreover, treatment with CCE strongly suppressed nuclear factor-${\kappa}B$ (NF-${\kappa}B$) promoter-driven expression in LPS-treated RAW 264.7 cells. CCE treatment blocked nuclear translocation of the p65 subunit of NF-${\kappa}B$ by preventing proteolytic degradation of inhibitor of ${\kappa}B-{\alpha}$. These results indicate that CCE regulates iNOS and COX-2 expression through NF-${\kappa}B$-dependent transcriptional control, and identifies potential candidates for the treatment or prevention of inflammatory diseases.

Anti-Inflammatory Effects of 15Hz Electroacupuncture on the Carrageenan-Injected Rat (Carrageenan 유발염증에 대한 15Hz 전침의 효과에 대한 연구)

  • Han, You-jin;Lee, Yong-tae;Jang, Kyung-jeon
    • Journal of Acupuncture Research
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    • v.20 no.3
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    • pp.166-176
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    • 2003
  • Objective : The aim of this study is to investigate the anti-inflammatory effects of 15Hz electroacupuncture(EA) on carrageenan-injected rats. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw. Methods : Bilateral EA stimulation with 15 Hz were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles for a total of 30 min duration in carrageenan-injected rats. Results: The developing edema was measured 30 minutes interval afer carrageenan injection and 15 Hz EA stimulation presented significant edema inhibition. Three hours after carrageenan injection, prostaglandin $E_2(PGE_2)$ and nitric oxide(NO) levels were measured. The 15Hz EA stimulation significantly inhibited $PGE_2$ and NO production in the right paw. The pro-inflammatory mRNA expression such as cyclooxygenases(COX)-2 and interleukin(IL)-$1{\beta}$ were slightly down-regulated by EA stimulation. The number of COX-2, IL-$1{\beta}$, tumor necrosis factor-${\alpha}$ immunoreactive cells were abundantly observed in paw edema. But these cells were decreased in nmber according to anti-edema effect of 15Hz EA. Conclusions: These results indicate that 15Hz EA stimulation have an alleviation action against carrageenan-induced edema and local inflammation.

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The Effect of Gyejibokryunghwan on Fracture Union in Tibia-fractured Rats (계지복령환(桂枝茯苓丸)이 흰쥐의 골절유합에 미치는 영향)

  • Yoon, Jeong-Won;Kim, Soon-Joong
    • Journal of Korean Medicine Rehabilitation
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    • v.29 no.4
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    • pp.1-14
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    • 2019
  • Objectives The object of this study was to assess the effect of Gyejibokryunghwan (GBH) on anti-oxidant and anti-inflammatory activities in RAW 264.7 cells and on factors associated with fracture union in tibia-fractured rats. Methods The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity was measured to assess anti-oxidant activity. The production of nitric oxide (NO), interleukin-6 (IL-6), interleukin-$1{\beta}$ ($IL-1{\beta}$) and tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$) in the RAW 264.7 cells were measured to assess anti-inflammatory activity. The production of osteocalcin, calcitonin, carboxy-terminal telepeptides of type II collagen (CTXII), transforming growth factor-${\beta}$ ($TGF-{\beta}$), bone morphogenetic protein-2 (BMP-2) in serum of tibia-fractured rats were measured to assess the effects of fracture union. X-rays were taken every two weeks from 0 to 4th week to assess fracture union effect. Results DPPH radical scavenging activity of GBH was increased according to concentration of GBH in RAW 264.7 cell. NO, prostaglandin $E_2$ ($PGE_2$), IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were significantly decreased, indicating anti-inflammatory effect. Osteocalcin, calcitonin, $TGF-{\beta}$ were significantly increased in the experimental groups. CTXII was significantly decreased in the experimental groups. BMP-2 was not significantly changed in the experimental groups. The X-ray showed that the experimental group has better healing effects on tibia-fractured rats than control group. Conclusions From above result, GBH has an effect on anti-oxidant, anti-inflammatory activities in RAW 264.7 cells. GBH showed significant results in factors related with fracture union and radiologic examination. In conclusion, GBH can help fracture union and it well be expected to be used actively in clinics.

Analgesic Effect and Inhibition of Prostaglandin $E_2$ Activity and Pro-inflammatory Cytokines Production by Ethyl Alcohol Extract from New Herbal Formula (신규 생약 복합추출물에 의한 Prostaglandin $E_2$ 활성억제, 염증성 Cytokine 생성 저해 및 진통 작용에 관한 연구)

  • Kwon, Soon-Yong;Lee, Hwa-Sung;Lee, Soon-Hyuck;Im, Gun-Il;Kim, Si-Na;Kim, Hee-Seok;Hwang, Sung-Wan;Hwang, Sung-Yeoun
    • Korean Journal of Pharmacognosy
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    • v.37 no.3
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    • pp.136-142
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    • 2006
  • New herbal formula (NHF) is the ethanol extract mixture of Puerariae radix, Artemisia capillaries and Perilla frutescens. We have Investigated the effects on anti-inflammation by NHF and attempted acetic acid induced writhing to verify the analgesic effect. Macrophages and chondrocytes were obtained from mouse and rabbit. Inflammation was induced bγ interleukin-1, tumor necrosis $factor-{\alpha}$, $interferon-{\gamma}$, and lipopolysaccharide. NHF showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, $PGE_2$ production, NO production, and MMP-9 expression in rabbit articular chondrocyte. In the writhing test, NHF exhibited a dose-dependent inhibition of writhing. Futhermore, NHF increased the activity of SOD. NHF have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for curing of osteoarthritis.