• Title/Summary/Keyword: anti-inflammatory$NF-{\kappa}B$

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Screening of Useful Plants with Anti-inflammatory and Antioxidant Activity (항염증 및 항산화 활성 보유 유용 식물 탐색)

  • Lee, Seung-Eun;Choi, Jehun;Lee, Jeong-Hoon;Noh, Hyung-Jun;Kim, Geum-Sook;Kim, Jinkyung;Chung, Hae-Young;Kim, Seung-Yu
    • Korean Journal of Plant Resources
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    • v.26 no.4
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    • pp.441-449
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    • 2013
  • This study was conducted to select some useful plants as functional material candidates. A total of 38 plants were preliminarily screened for the anti-inflammatory and antioxidant activities. The preliminarily selected 8 plants were further investigated to verify the in vitro inhibitory effect on inflammation and oxidative stress. Boehmeria platanifolia (root), Carpinus coreana (branch), and Eupatorium japonicum (leaf) inhibited the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Eupatorium japonicum (leaf) suppressed the expression of cyclooxygenase-2 (COX-2), whereas Boehmeria platanifolia (root) and Prunus yedoensis (branch) inhibited the transcription of nuclear factor-kappa B (NF-${\kappa}B$). Treatment with the extracts ($2.5{\sim}20{\mu}g/ml$) of Abutilon theophrasti (leaf, flower/seed) and Hemistepta lyrata (stem) did not show toxicity on RAW 264.7 cell proliferation, but treatment with $2.5{\mu}g/ml$ of Boehmeria platanifolia (root) exhibited cell toxicity. Carpinus coreana (branch) and Prunus yedoensis (branch) showed potent scavenging activities on peroxynitrite. Akebia quinata (flower), Carpinus coreana (branch), and Prunus yedoensis (branch) effectively inhibited reactive oxygen species (ROS). Abutilon theophrasti (leaf), Boehmeria platanifolia (root), Carpinus coreana (branch), and Eupatorium japonicum (leaf) exhibited strong inhibitory capacity with regard to nitric oxide (NO) production. The results suggested that Abutilon theophrasti (leaf) has in vitro anti-inflammatory and antioxidant activities, and that is a useful functional material candidate.

The Effects of Gamisipjeon-tang on the Skin Regeneration of Deep Second Degree Burns in Mice

  • Yu, Hyun-Jung;Hong, Seung-Ug
    • The Journal of Korean Medicine
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    • v.31 no.3
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    • pp.107-121
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    • 2010
  • Objective: This study aimed to ascertain the curative effects of Gamisipjeon-tang (GST) used for wound healing on the skin regeneration of deep second degree burns in mice. Material & Methods: In vitro, the $I{\kappa}B$ kinase (IKK) mRNA expression, inducible nitric oxide synthase (iNOS) mRNA expression, and cyclooxygenase-2 (COX-2) mRNA expression in the GST concentration from 1 mg/$m{\ell}$ to 10 mg/$m{\ell}$ were measured. In vivo, the mice were divided into four groups : the normal group, the BE group (burn-elicited group, control group), the DC group (Duoderm CGF-treated group after burn elicitation), and the GST group (Gamisipjeon-tang treated group after burn elicitation). To determine the anti-inflammatory effects, nuclear factor (NF)-${\kappa}B$ p65, iNOS, COX-2 positive reaction were measured by immunohistochemistry. To estimate the skin regenerative effects, change of burn area, 5-bromo-2'-deoxyuridine (BrdU), and fibroblast growth factor (FGF) positive reaction were analyzed. Results: In vitro, the iNOS, IKK, COX-2 mRNA expression decreased according to the increase of GST concentration. The significant decrease of COX-2, iNOS, NF-${\kappa}B$ positive reaction were the highest in the GST group, followed by the DC group and the BE group (p<0.05). The diameter of burn area was significantly decreased in the GST group as compared to that in the DC and BE group (p<0.05). The BrdU and FGF positive reaction increased more significantly in the GST group than in the DC group, and more significantly in the DC group than in the BE group on the 3rd and 7th day after burn (p<0.05). FGF positive reaction increased in the BE and DC group, whereas it decreased significantly in the GST group on the 14th day (p<0.05). The BrdU positive reaction increased in the BE group, whereas it decreased significantly in the DC and GST group on the 14th day (p<0.05). Conclusions: This study shows that GST could decrease the inflammatory response and accelerate the skin regeneration as compared to the duoderm CGF in mice with deep second degree burns.

The Molecular Mechanism of Baicalin on RANKL-induced Osteoclastogenesis in RAW264.7 Cells

  • Ko, Seon-Yle
    • International Journal of Oral Biology
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    • v.38 no.2
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    • pp.67-72
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    • 2013
  • This study examined the anti-osteoclastogenic effects of baicalin on receptor activator of NF-${\kappa}$B ligand (RANKL)-induced RAW264.7 cells. Baicalin is a flavonoid that is produced by Scutellaria baicalensis and is known to have multiple biological properties, including antibacterial, anti-inflammatory and analgesic effects. The effects of baicalin on osteoclasts were examined by measuring 1) cell viability; 2) the formation of tartrate-resistant acid phosphatase (TRAP) (+) multinucleated cells; 3) RANK/RANKL signaling pathways and 4) mRNA levels of osteoclast-associated genes. Baicalin inhibited the formation of RANKL-stimulated TRAP (+) multinucleated cells and also suppressed the RANKL-stimulated activation of p-38, ERK, cSrc and AKT signaling. Baicalin also inhibited the RANKL-stimulated degradation of $I{\kappa}B$ in RAW264.7 cells. In addition, the RANKL-stimulated induction of NFATc1 transcription factors was found to be abrogated by this flavonoid. Baicalin was further found to decrease the mRNA expression of osteoclast-associated genes, including carbonic anhydrase II, TRAP and cathepsin K in the RAW264.7 cells. Our data thus demonstrate that baicalin inhibits osteoclastogenesis by inhibiting the RANKL-induced activation of signaling molecules and transcription factors in osteoclast precursors.

Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils

  • Bae, Minkyung;Jang, Sungil;Lim, Joo Weon;Kang, Jieun;Bak, Eun Jung;Cha, Jeong-Heon;Kim, Hyeyoung
    • Journal of Ginseng Research
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    • v.38 no.1
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    • pp.8-15
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    • 2014
  • Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-${\kappa}B$. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-$1{\beta}$, and iNOS; protein level of phospho-$I{\kappa}B{\alpha}$(which reflects the activation of NF-${\kappa}B$); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-$1{\beta}$, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of $I{\kappa}B{\alpha}$ and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of poly-morphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pyloriinduced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-$1{\beta}$, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa.

Anti-inflammatory Effect of Isaria sinclairii Glycosaminoglycan in an Adjuvant-treated Arthritis Rat Model

  • Ahn, Mi Young;Jee, Sang Duck;Hwang, Jae Sam;Yun, Eun Young;Ahn, Kwang Seok;Kim, Yeong Shik
    • Toxicological Research
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    • v.29 no.3
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    • pp.195-201
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    • 2013
  • The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-${\kappa}B$ activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin $E_2$-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-${\alpha}$ production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

Protective Effect of Paulownia tomentosa Fruits in an Experimental Animal Model of Acute Lung Injury

  • Kim, Seong-Man;Ryu, Hyung Won;Kwon, Ok-Kyoung;Min, Jae-Hong;Park, Jin-Mi;Kim, Doo-Young;Oh, Sei-Ryang;Lee, Seung Jin;Ahn, Kyung-Seop;Lee, Jae-Won
    • Microbiology and Biotechnology Letters
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    • v.50 no.2
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    • pp.310-318
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    • 2022
  • The fruits of Paulownia tomentosa (Thunb.) (PT) Steud. have been reported to exert a variety of biological activities. A previous study confirmed that compounds isolated from PT fruits (PTF) exerted anti-inflammatory effects on TNF-α-stimulated airway epithelial cells. However, there is no report on the protective effects of PTF on acute lung injury (ALI). Here, we examined the ameliorative effects of PTF in an experimental animal model of lipopolysaccharide (LPS)-induced ALI. In ALI mice, increased levels of inflammatory cell influx were confirmed in the lungs of mice, and an increase of microphage numbers, TNF-α, IL-6 and MCP-1 production and protein content were detected in mouse bronchoalveolar lavage fluid. However, these increases were significantly reversed with PTF pretreatment. In addition, PTF inhibited the increased expression of iNOS and COX-2 in the lungs of ALI mice. Furthermore, the upregulation of MAPK and NF-κB activation was decreased in the lungs of ALI mice by PTF. In the in vitro experiment, PTF pretreatment exerted an anti-inflammatory effect by inhibiting the secretion of nitric oxide, TNF-α and IL-6 in LPS-stimulated RAW264.7 macrophages. Collectively, these results indicated that PTF has ameliorative effects on airway inflammation in an experimental animal model of ALI.

Anti-Oxidative and Anti-Inflammatory Effects of Malus huphensis, Ophiorrhiza cantonensis, and Psychotria rubra Ethanol Extracts (Malus huphensis, Ophiorrhiza cantonensis, Psychotria rubra 에탄올 추출물의 항산화 및 항염증 활성)

  • Jin, Kyong-Suk;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.42 no.3
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    • pp.275-284
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    • 2014
  • This study was orchestrated with the purpose of uncovering new nutraceutical resources possessing biological activities in the plant kingdom. To fulfill our objective, we analyzed several Chinese plants and selected three possessing powerful anti-oxidative activities. The anti-oxidative and anti-inflammatory effects these three Chinese plants, Malus hupehensis, Ophiorrhiza cantonensis, and Psychotria rubra ethanol extracts were then evaluated. First of all, they possessed potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl, similar with that of ascorbic acid, used as a positive control. Moreover, they inhibited lipopolysaccharide (LPS)- and hydrogen peroxide-induced reactive oxygen species, in a dose-dependent manner, in RAW 264.7 cells. Also, they induced the expression of an anti-oxidative enzyme, heme oxygenase 1, and its upstream transcription factor, nuclear factor-E2-related factor 2. Furthermore, they suppressed LPS-induced nitric oxide (NO) formation, without cytotoxicity. The inhibition of NO formation was the result of the down regulation of inducible NO synthase (iNOS). The suppression of NO and iNOS by the three extracts might be the result of modulation by the upstream transcription factors, nuclear factor ${\kappa}B$ and activator protein-1. Taken together, these results indicate that these three Chinese plants possess potent anti-oxidative and anti-inflammatory activities. Therefore, they might be utilized as promising materials in the field of nutraceuticals.

Effects of salmon DNA fraction in vitro and in a monosodium iodoacetate-induced osteoarthritis rat model

  • Ra, Ho Jong;Oh, Mi Young;Kim, Hee Ju;Lee, Seung Yong;Eom, Dae Woon;Lee, Suk Kyu;Kim, Su-Nam;Chung, Kyu Sung;Jang, Hyuk Jai
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.163-172
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    • 2018
  • PRF001 is a fragmented DNA polymer extracted from the testes of salmon. The purpose of this study was to assess the anti-inflammatory effect of PRF001 in vitro as well as the protective effect of PRF001 intake against arthritis in a rat model. In vitro, cell survival and inflammatory markers after $H_2O_2$ treatment to induce cell damage were investigated in CHON-001 cells treated with different concentrations of PRF001. In vivo, osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA) into the knee joints of rats. After consumption of PRF001 (10, 50, or 100 mg/kg) for 4 weeks, inflammatory mediators and cytokines in articular cartilage were investigated. In vitro, the levels of inflammatory markers, $IL-1{\beta}$, $TNF-{\alpha}$, COX-2, iNOS, and PGE2, were significantly suppressed by PRF001 treatment. In vivo, the inflammatory mediators and cytokines, $IL-1{\beta}$, p-Erk1/2, $NF-{\kappa}B$, $TNF-{\alpha}$, COX-2, and PGE2, as well as MMP3 and MMP7, which have catabolic activity in chondrocytes, were decreased in the MIA-induced osteoarthritic rats following intake of PRF001. Histological analysis revealed that PRF001 had a protective effect on the articular cartilage. Altogether, these results demonstrated that the anti-inflammatory property of PRF001 contributes to its protective effects in osteoarthritis through deregulating $IL-1{\beta}$, $TNF-{\alpha}$, and subsequent signals, such as p-Erk1/2, $NF-{\kappa}B$, COX-2, PGE2, and MMPs.

Research of the Anti-inflammatory Effects of Hwadokdan on Raw 264.7 Cells (Raw 264.7 세포에서 화독단(化毒丹)의 항염증 효능에 대한 연구)

  • Shin, Ki Seok;Hwangbo, Min;Jee, Seon Young
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.35 no.3
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    • pp.36-47
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    • 2022
  • Objectives : The purpose of this study was to evaluate the anti-Inflammatory effect of Hwadokdan(HDD) extracted with water. Methods : We pretreated LPS-activated Raw 264.7 cell with HDD and anti-inflammatory effect of HDD is investigated by measuring NO production, relative iNOS, and TNF-α, IL-6, IL-1β, PGE2 productions level, p-IκBα, IκBα, NFκB. Results : HDD reduced NO production and iNOS protein, TNF-α, IL-6 level at concentration of 100㎍/㎖ and 300㎍/㎖ in LPS-activated Raw 264.7 cell significantly. There wasn't a significant cytotoxicity in MTT assay. And HDD reduced IL-1β level at concentration of 300㎍/㎖ in LPS-activated Raw 264.7 cell significantly. HDD reduced p-IκBα and NFκB protein level at concentration of 300㎍/㎖ in LPS-activated Raw 264.7 cell significantly. And HDD enhanced IκBα protein level at concentration of 100㎍/㎖ and 300㎍/㎖ in LPS-activated Raw 264.7 cell significantly. Conclusions : These suggests that HDD can be used as a therapeutic drug for various inflammatory diseases.

Anti-inflammatory Metabolites of Agrimonia pilosa Ledeb. and Their Mechanism

  • Park, Mi Jin;Ryu, Da Hye;Cho, Jwa Yeoung;Kang, Young-Hwa
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.13-13
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    • 2018
  • The anti-inflammatory (INF) compounds (1-15) were isolated from Agrimonia pilosa Ledeb. (APL) by activity-guided isolation technique. The isolated compounds (1-15) were identified as quercetin-7-O-rhanmoside (1), apigenin-7-O-glycoside (2), kaempferol-7-O-glycoside (3), apigenin-7-O-[6"-(butyl)-glycoside] (4), querceitn (5), kaempferol (6), apigenin (7), apigenin-7-O-[6"-(pentyl)-glycoside] (8), agrimonolide (9), agrimonolide-6-O-glucoside (10), desmethylagrimonolide (11), desmethylagrimonolide-6-O-glucoside (12), luteolin (13), vitexin (14) and isovitexin (15). Flavonoids, compound 2, 3, 11, and 14-15 have been found in APL for the first time. Furthermore, two novel flavone derivatives, compound 4 and 8, have been isolated inceptively in plant. In the no cytotoxicity concentration ranges of $0-20{\mu}M$, nitric oxide (NO) production level of 1-15 was estimated in LPS-treated Raw 264.7 macrophage cells. The flavone aglycones, 7 (apigenin, $IC_{50}=3.69{\pm}0.34{\mu}M$), 13 (luteolin, $IC_{50}=4.62{\pm}0.43{\mu}M$), 6 (kaempferol, $IC_{50}=14.43{\pm}0.23{\mu}M$) and 5 (quercetin, $IC_{50}=19.50{\pm}1.71{\mu}M$), exhibited excellent NO inhibitory (NOI) activity in dose-dependent manner. In the structure activity relationship (SAR) study of apigenin-derivatives (APD), apigenin; Api, apigenin-7-O-glucoside; Api-G, apignenin-7-O-[6"-(butyl)-glycoside]; Api-BG and apignenin-7-O-[6"-(pentyl)-glycoside]; Api-P, from APL on INF activity was investigated. The INF mediators level such as NO, INF-cytokines, NF-KB proteins, iNOS and COX-2 were sharply increased in Raw 264.7 cells by LPS. When pretreatment with APD in INF induced macrophages, NOI activity of Api was most effective than other APD with $IC_{50}$ values of $3.69{\pm}0.77{\mu}M$. And the NOI activity was declined in the following order: Api-BG ($IC_{50}=8.91{\pm}1.18{\mu}M$), Api-PG ($IC_{50}=13.52{\pm}0.85{\mu}M$) and API-G ($IC_{50}=17.30{\pm}0.66{\mu}M$). The NOI activity of two novel compounds, Api-PG and Api-BG were lower than their aglycone; Api, but more effective than Api-G (NOI: Api-PG and Api-BG). And their suppression ability on INF cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA showed the similar tendency. Therefore, the anti-INF mechanism study of Api-PG and Api-BG on nuclear factor-kappa B ($NF-{\kappa}B$) pathway, representative INF mechanism, was investigated and Api was used as positive control. Api-BF was more effectively prevent the than phosphorylation of $pI{\kappa}B$ kinase (p-IKK) and p65 than Api-PG in Raw 264.7 cells. In contrast, Api-PG and Api-BG were not reduced the phosphorylation of inhibitor of kappa B alpha ($I{\kappa}B{\alpha}$). Moreover, pretreatment with Api-PG and Api-BG, dose-dependently inhibited LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNAs and proteins in macrophage cells, and their expression were correlated with their NOI activity. Therefore, APL can be utilized to health promote agent associated with their AIN metabolites.

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