• 동의생리병리학회지
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• 제27권6호
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• pp.795-801
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• 2013

The purpose of this study is to investigate effects of White Ginseng-Ejung-tang (EG) and Red Ginseng-Ejung-tang (ER) water extract on production of various cytokines such as interleukin (IL)-21, IL-25, IL-$28{\beta}$, erythropoietin (EPO), Exodus-2, monocyte chemotactic protein (MCP)-5, macrophage inflammatory protein (MIP)-$3{\alpha}$, MIP-$3{\beta}$, Fractalkine, and TARC in RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS). Levels of cytokines were measured by High-throughput multiplex bead array cytokine assay based on xMAP (multi-analyte profiling beads) technology. ER significantly decreased levels of IL-21, IL-25, IL-$28{\beta}$, EPO, Exodus-2, MCP-5, MIP-$3{\alpha}$, MIP-$3{\beta}$, TARC, and fractalkine for 24 h incubation at the oncentrations of 25 and 100 ${\mu}g/mL$ in LPS-induced RAW 264.7 (P < 0.05). But EG did not show any significant effect. These results suggest that ER has anti-inflammtory property related with its inhibition on the production of IL-21, IL-25, IL-$28{\beta}$, and chemokines such as EPO, MCP-5, MIP-$3{\alpha}$, MIP-$3{\beta}$, Fractalkine, Exodus-2, and TARC in LPS-induced macrophages.

• Biomolecules & Therapeutics
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• 제16권4호
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• pp.385-393
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• 2008

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we evaluated the effects of the methanol extract of Polytrichum commune Hedw (PCM) (Polytrichaceae) on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines release in murine macrophage cell line RAW 264.7. PCM potently inhibits the production of NO, $PGE_2$, tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-6. Consistent with these results, PCM also concentration-dependently inhibited LPS-induced inducible NO synthase (iNOS) and cyclooxygase (COX)-2 at the protein levels, and iNOS, COX-2, TNF-$\alpha$ and IL-6 at the mRNA levels without an appreciable cytotoxic effect on RAW 264.7 macrophag cells. Furthermore, PCM inhibited LPS-induced nuclear factor-kappa B (NF-$\kappa$B) activation as determined by NF-$\kappa$B reporter gene assay, and this inhibition was associated with a decrease in the nuclear translocation of p65 and p50 NF-$\kappa$B. Taken together, these results suggest that PCM may play an anti-inflammatory role in LPS-stimulated RAW 264.7 macrophages through the inhibitory regulation of iNOS, COX-2, TNF-$\alpha$ and IL-6 via NF-$\kappa$B inactivation.

• Nutrition Research and Practice
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• 제7권6호
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• pp.460-465
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• 2013

The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/$10{\mu}g/kg$ body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.

• 치위생과학회지
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• 제15권6호
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• pp.753-760
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• 2015

숙주 면역 반응과 면역 체계는 치주 질환에 대한 개인의 감수성의 주요 원인이다. 세균 감염과 흡연은 치주 조직의 파괴의 원인과 진행에 관여하는 중요한 환경 위험 요인이다. 따라서, 본 연구는 사람 치주인대세포에서 LPS와 니코틴이 전염증성 사이토카인인 iNOS/COX-2의 발현과 NO/$PGE_2$ 생산에 미치는 영향을 알아보고 NFATc1가 어떤 기전으로 항염작용을 하는지 밝히고자 하였다. LPS와 니코틴을 처리한 사람 치주인대세포에서 iNOS/COX-2의 발현과 함께 NO/$PGE_2$ 생산은 증가되었다. NFATc1 inhibitor인 CsA는 LPS와 니코틴에 의해 유도되는 iNOS/COX-2의 발현과 함께 NO/$PGE_2$ 생산을 감소시켰다. 이러한 연구 결과로 볼 때, NFAT signaling pathway가 LPS와 니코틴에 의한 iNOS/COX-2의 발현을 조절하여 NO/$PGE_2$ 매개 염증에 대해 방어할 수 있다고 생각된다.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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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.

• 한방재활의학과학회지
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• 제33권4호
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• pp.1-14
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• 2023

Objectives The anti-inflammatory and anti-arthritic effects of Youngseonjeatonguem (靈仙除痛飮, YSJTU) was evaluated in a cellular model using RAW264.7 macrophages, which are involved in osteoarthritis (OA), and an animal model using Sprague-Dawley (SD) rats, and a possible mechanism of anti-arthritic actions of YSJTU was presented. Methods RAW264.7 macrophages were activated by lipopolysaccharide (LPS). The production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-𝛼, interleukin [IL]-1𝛽, and IL-6) and inflammatory mediators (nitric oxide [NO] and prostaglandin E2 [PGE2]) was determined by ELISA and Griess assay, respectively. Western blot was performed to determine inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. OA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joint of SD rats. Results In RAW264.7 macrophages, YSJTU reduced LPS-induced production of TNF-𝛼, IL-1𝛽, and IL-6. In addition, YSJTU inhibited LPS-induced production of NO and PGE2 by suppressing iNOS and COX-2 expression. In SD rats, YSJTU improved MIA-induced OA by reducing swelling, skin heat, and cartilage degradation. In addition, YSJTU reduced serum levels of TNF-𝛼, IL-1𝛽, and IL-6, along with its significant decrease in serum levels of NO and PGE2. Conclusions These results suggest that YSJTU may exert anti-arthritic effect, at least in part, by inhibiting macrophage-mediated joint inflammation.

• 대한한의학회지
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• 제39권1호
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• pp.63-74
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• 2018

Objectives: Periodontitis is an inflammatory disease with the destruction of periodontal ligament, alveolar bone loss and inflammation of gingva, leading to teeth loss. Eclipta prostrata L. (Ecliptae Herba) has been used to treat the inflammatory disease as a Korean traditional medicine. The aim of this study is to investigate the effects of E. prostrata L. on periodontitis. Methods: E. prostrata L. was extracted with water and lyophilized. The aqueous extract of E. prostrata L. (EP) was topically applied to the periodontal lesion for 2 weeks. To induce the periodontitis, a 3-0 nylon ligature was placed around the cervix of the lower first molar in rat. Rats were divided into 3 groups (n = 7); NL group (non-ligatured and non-treated), L group (ligatured and vehicle-treated) and EP group (ligatured and EP-treated). After sacrifice, the mandibles was dissected and stained with methylene blue solution to analyze the alveolar bone loss. The expression of MMP-9 was determined in gingival tissues. To confirm the effect of EP on recovery of gingiva, mRNA expressions of type I pro-collagen and MMP-9 levels were investigated in LPS-treated HS68 fibroblast cells. In addition, inflammatory mediators were evaluated in LPS-treated RAW264.7 cells. Results: Alveolar bone loss was significantly inhibited by EP treatment. The mRNA expression of MMP-9 was attenuated in rats treated with EP. In addition, treatment with EP increased the expression of type I pro-collagen, while the expression of MMP-9 was decreased in LPS-stimulated HS68 fibroblast cells. Furthermore, EP down-regulated the LPS-induced IL-6, $TNF-{\alpha}$, COX-2 and iNOS production in RAW264.7 cells. Conclusions: These results suggest that EP have ameliorative effects on periodontitis through inhibiting alveolar bone loss and modulating the inflammatory mediators. Therefore, E. prostrata L. may be an alternative on patients with periodontitis.

• 한방안이비인후피부과학회지
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• 제23권1호
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• pp.118-134
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• 2010

Objective: Yang Geouk San Hwa - Tang (YGSHT) has been widely used in Sasang Constitutional Medicine of Korea for treatment of acute inflammatory symptom, such as palatine tonsillitis, polydipsia, headache, papule, pimple however, the mechanism of its anti-inflammatory activity has not been clarified. In this study, therefore, we investigated the mechanism of the inhibitory effect of YGSHT on LPS-induced inflammation. Materials and methods: The effect of YGSHT was analyzed by ELISA, RT-PCR and Western blotting in LPS-stimulated RAW264.7 cells. Results: We found that YGSHT suppressed not only the production of pre-inflammatory cytokines (IL-$1{\beta}$ and TNF-$\alpha$), the generation of nitric oxide (NO) and prostaglandin E (PGE)2, but also the mRNA expression of pre-inflammatory cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2. Furthermore, YGSHT was shown to inhibit the phosphorylation of ERK1/2 and JNK1/2 and the activation and translocation of NF-kB from cytosol to nuclear in LPS-stimulated RAW264.7 cells. Conclusions: These results suggest that YGSHT exerts an anti-inflammatory effect through the regulation of the ERK1/2 and JNK1/2 pathway and NF-kB pathway, thereby decreasing production of pre-inflammatory cytokines, NO, and PGE2.

• 대한본초학회지
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• 제24권1호
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• pp.169-178
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• 2009

Objectives : In this study, the effects of ethylacetate extract of Ostericum koreanum on inflammation in RAW264.7 cells were investigated. Methods : Dried roots of Ostericum koreanum was extracted with 80% methanol for 24 h, and then fractionated with n-butanol, n-hexan and ethylacetate. RAW264.7 cells, a mouse macrophage line were incubated with different concentrations of the extract for 30 min and then stimulated with LPS at indicated times. Cell toxicity was determined by MTT assay. The concentrations of nitric oxide (NO) and prostaglandin E2 ($PGE_2$) were measured by Griess assay and enzyme immunoassay (EIA), respectively. The expressions of inducible nitric oxide synthease (iNOS) and cyclooxyganase (COX) -2 mRNA and protein were determined by RT-PCR and Western blot. Results : The methanol extract of Ostericum koreanuman and its fractions were significantly inhibited the NO and PGE2 productions in LPS-stimulated RAW264.7 cells. Among the fractions of Ostericum koreanuman the ethylacetate fraction was more strongly inhibited NO and $PGE_2$ productions compared with other fractions. The ethylacetate fraction was also suppressed LPS-induced mRNA expressions of iNOS and its protein levels in RAW264.7 cells. Conclusions : This study suggests that the ethylacetate fraction of Ostericum koreanum may have an anti-inflammatory property through suppressing inflammatory mediator productions in activated macrophages, suggesting have a therapeutic potential for the treatment of various inflammatory diseases.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.146-156
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• 2018

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), and cytokines including tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of $NF-{\kappa}B$ p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.