• Title/Summary/Keyword: Anti-inflammatory mechanism

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Inhibitory Effects of β-Glycyrrhetinic Acid on Tumor Necrosis Factor-α Production in RAW 264.7 Cells

  • Park, Kyoung-Sik
    • Journal of Applied Biological Chemistry
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    • v.53 no.3
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    • pp.147-153
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    • 2010
  • $\beta$-glycyrrhetinic acid (GA), the active principle of licorice (Glycyrrhiza glabra L.) has been reported to exhibit anti-inflammatory properties in different animal models. In this study, the effects of GA on the production of inflammatory mediators including tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-6, nitric oxide (NO), and prostaglandin E (pGE)-2 were examined in RAW 264.7 cells in vitro. Furthermore, to elucidate a possible mechanism for the inhibitory effect of GA on the production of TNF-$\alpha$, it was investigated whether the treatment of GA affects the I-${\kappa}B{\alpha}$ degradation and subsequent nuclear translocation of NF-${\kappa}B$. Various inflammatory responses were induced in the culture system by treating with a lipopolysaccharide (LPS). GA showed anti-inflammatory activities in dose-dependant manner with $IC_{50}$ of $5.4{\mu}M$ by inhibiting the production of TNF-$\alpha$ in RAW 264.7 cells. In addition, the treatment of GA blocked both I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$ from cytosol to nucleus. However, it did not affect the production of IL-6, NO, and PGE-2, implying the direct blocking of the production of TNF-$\alpha$ resulting from both the I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$. This finding might provide the underlying mechanism to explain the reported anti-inflammatory activities of GA in animal models.

Fisetin Suppresses Macrophage-Mediated Inflammatory Responses by Blockade of Src and Syk

  • Kim, Jun Ho;Kim, Mi-Yeon;Kim, Jong-Hoon;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.23 no.5
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    • pp.414-420
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    • 2015
  • Flavonoids, such as fisetin (3,7,3',4'-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-${\alpha}$, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-${\kappa}B$. In agreement, the upstream phosphorylation events for NF-${\kappa}B$ activation, composed of Src, Syk, and I${\kappa}B{\alpha}$, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.

Antioxidative, Anti-inflammatory Effects of Jibaekjihwang-tang (zhibaidihuang-tang) on Osteoarthritic Rat Model (지백지황탕(知栢地黃湯)의 골관절염 Rat 모델에 대한 항산화, 항염증 효과)

  • Woo, Chang-Yun;Kim, Young-Jun;Woo, Chang-Hoon
    • Journal of Korean Medicine Rehabilitation
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    • v.30 no.2
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    • pp.1-18
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    • 2020
  • Objectives This study intended to evaluate antioxidative, anti-inflammatory effects of Jibaekjihwang-tang on monosodium iodoacetate (MIA)-induced osteoarthritic rat model and investigate the potential mechanism. Methods Jibaekjihwang-tang (100 or 200 mg/kg body weight) was orally administered once daily for 2 weeks days from day 7 after intra-articular MIA injection. And blood analysis, the histologic examinations were performed. Moreover, protein expressions related to anti-oxidant and cartilage degradation and anti-inflammatory cytokines were measured by western blot analysis in cartilaginous tissue. Results Jibaekjihwang-tang reduced serum inflammatory cytokines such as tumor necosis factors-α and interleukin-6. Furthermore, the increase of anti-oxidant enzymes reversed the oxidative stress caused by MIA. Meanwhile, Jibaekjihwang-tang suppressed MIA-induced inflammation and cartilage degradation in cartilaginous tissue. Conclusions Jibaekjihwang-tang alleviated MIA-induced inflammation. Jibaekjihwang-tang was associated with a protective effect on cartilage and by reducing inflammation and cartilage degradation. These findings provide new approaches for understanding osteoarthritis therapy.

Studies on the anti-infiammatory activity and its mechanism of daidzein (Daidzein의 항염작용과 그 작용기전에 관한 연구 (I))

  • 허인회;이상준;김형춘
    • YAKHAK HOEJI
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    • v.31 no.3
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    • pp.154-163
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    • 1987
  • Daidzein and its methyl derivatives were synthesized and their anti-inflammatory activities were examined. Daidzein suppressed the carrageenin-induced edema, but its methyl derivatives showed decrease or abolition of the anti-inflammatory effect. Daidzein did not significantly suppress the complete Freund's adjuvant-induced arthritis, and the mixed phlogistics (histamine+serotonin)-induced edema. Daidzein inhibited the leukocyte emigration and protein exudation when it was administered into the CMC pouch at low doses (5,25mg/pouch). Daidzein significantly suppressed the cotton-pellet granuloma formation.

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Inhibitory effects of resveratrol analogs on lipopolysaccharide-induced cyclooxygenase-2 activity in RAW264.7 cells

  • Park, Eun-Jung;Min, Hye-Young;Park, Jae-Eun;Kim, Sang-Hee;Lee, Sang-Kook
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.245.1-245.1
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    • 2002
  • It has been known that resveratrol, a phytoalexin present in grapes mainly, has antioxidant. anti-inflammatory, and cancer chemopreventive activity. One mechanism of its anti-inflammation and cancer prevention is considered to modulate cyclooxygense-2 (COX-2) activity. Since COX-2 plays an important role in inflammation and carcinogenesis, the potential COX-2 inhibitors have been considered as anti-inflammatory or cancer chemopreventive agents. (omitted)

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New Anti-Inflammatory Formulation Containing Synurus deltoides Extract

  • Choi, Yong-Hwan;Son, Kun-Ho;Chang, Hyeun-Wook;Bae, Ki-Hwan;Kang, Sam-Sik;Kim, Hyun-Pyo
    • Archives of Pharmacal Research
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    • v.28 no.7
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    • pp.848-853
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    • 2005
  • Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1 % inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7 -day model of multiple treatment of TPA (38.1 % inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin $E_2$ production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

Anti-inflammatory Effect of Heracleum moellendorffii Roots through the Inhibition of NF-κB and MAPK Signaling, and Activation of ROS/Nrf2/HO-1 Signaling in LPS-stimulated RAW264.7 Cells

  • Park, Su Bin;Kim, Ha Na;Kim, Jeong Dong;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.66-66
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    • 2019
  • Heracleum moellendorffii roots (HM-R) have been long treated for inflammatory diseases such as arthritis, backache and fever. However, an anti-inflammatory effect and the specific mechanism of HM-R were not yet clear. In this study, we for the first time explored the anti-inflammatory of HM-R. Results: HM-R dose-dependently blocked LPS-induced NO and PGE2 production. In addition, HM-R inhibited LPS-induced overexpression of iNOS, COX-2, $IL-1{\beta}$ and IL-6 in RAW264.7 cells. HM-R inhibited LPS-induced $NF-{\kappa}B$ signaling activation through blocking $I{\kappa}B-{\alpha}$ degradation and p65 nuclear accumulation. Furthermore, HM-R inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. HM-R increased nuclear accumulation of Nrf2 and HO-1 expression. However, NAC reduced the increased nuclear accumulation of Nrf2 and HO-1 expression by HM-R. In HPLC analysis, falcarinol was detected from HM-R as an anti-inflammatory compound. These results indicate that HM-R may exert anti-inflammatory activity by inhibiting $NF-{\kappa}B$ and MAPK signaling, and activating ROS/Nrf2/HO-1 signaling. From these findings, HM-R may have potential to be a candidate for the development of anti-inflammatory drugs.

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Anti-Inflammatory Effects of Hexane Fraction from White Rose Flower Extracts via Inhibition of Inflammatory Repertoires

  • Lee, Hwa-Jeong;Kim, Han-Seok;Kim, Seung-Tae;Park, Dong-Sun;Hong, Jin-Tae;Kim, Yun-Bae;Joo, Seong-Soo
    • Biomolecules & Therapeutics
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    • v.19 no.3
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    • pp.331-335
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    • 2011
  • In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-$1{\beta}$, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-${\kappa}B$ and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.

Suppressive Effect of Euryale ferox Salisbury Extracts on Inflammatory Response in LPS-stimulated RAW 264.7 Cells through the Antioxidative Mechanism (RAW 264.7 세포에서 Euryale ferox Salisbury 추출물의 항산화기전을 통한 산화적 스트레스.염증반응 억제효과 규명)

  • Kim, Young-Hwan;Lee, Min-Ja;Lee, Hye-Sook;Kim, Jung-Guk;Park, Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.2
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    • pp.202-211
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    • 2011
  • The stems and branchs of Euryale ferox Salisbury (EF), are used in Chinese herbal medicine for latent-heat-clearing, antipyretic, detoxicant and anti-inflammatory ailments. This plant is used worldwide for the treatment of many types of inflammatory disease including respiratory infections, diabetes mellitus, rheumatoid arthritis and play an important role in the immune reaction. Topical natural antioxidants are a useful strategy for the prevention of oxidative stress mediated inflammatory disease. Plants produce significant amounts of antioxidants to prevent the oxidative stress caused by photons and oxygen, therefore they represent a potential source of new compounds with antioxidant activity. This study was designed to evaluate whether EFEA (ethylacetate fraction of EF) may ameliorate oxidative stress and inflammatory status through the antioxidative mechanism in LPS-stimulated RAW 264.7 murine macrophage cell line. Treatment of RAW 264.7 cells with EFEA significantly reduced LPS-stimulated inflammatory response in a dose-dependent manner. In conclusion, the EF extracts have anti-inflammatory effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and chronic inflammatory disease.

Anti-inflammatory Effect and Mechanism of Citri Reticulatae Viride Pericarpium Water Extract (청피 물 추출물의 항염증 효과와 기전 연구)

  • Ahn, Tae-Seok;Hwang, Deok-Sang;Lee, Jin-Moo;Jang, Jun-Bock;Lee, Chang-Hoon
    • The Journal of Korean Obstetrics and Gynecology
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    • v.34 no.1
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    • pp.34-47
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    • 2021
  • Objectives: This study was designed to examine anti-inflammatory effect and mechanism of Citri Reticulatae Viride Pericarpium water extract (CRE). Methods: Cell cytotoxicity was tested with RAW 264.7 cells. To investigate anti-inflammatory effect of CRE in lipopolysaccharide (LPS)-induced RAW 264.7 cell, we measured nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). In addition, mitrogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) were examined by western blotting in LPS-induced RAW 264.7 cell with treated CRE. Results: In cytotoxicity analysis, CRE does not affect cell cytotoxicity. As compared with the control group, the expression of NO, PGE2, TNF-α, IL-6 were significantly decreased, and IL-10 was significantly increased in LPS-induced RAW 264.7 cell with treated CRE. As a result of Western blotting, there was concentration-dependent inhibition of pp38, pERK in MAPK pathway and significant reduction of pp65 in the NF-κB pathway. Conclusions: CRE might have anti-inflammatory effect in LPS-induced macrophages by promoting the production of IL-10.