• Title/Summary/Keyword: Inflammatory Factors

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IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling

  • Lee, Won-Jun
    • IMMUNE NETWORK
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    • v.11 no.4
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    • pp.223-226
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    • 2011
  • Although exercise-induced growth factors such as Insulin-like growth factor-I (IGF-I) are known to affect various aspects of physiology in skeletal muscle cells, the molecular mechanism by which IGF-I modulates anti-inflammatory effects in these cells is presently unknown. Here, we showed that IGF-I stimulation suppresses the expression of toll-like receptor 4 (TLR4), a key innate immune receptor. A pharmacological inhibitor study further showed that PI3K/Akt signaling pathway is required for IGF-I-mediated negative regulation of TLR4 expression. Furthermore, IGF-I treatment reduced the expression of various NF-${\kappa}B$-target genes such as TNF-${\alpha}$ and IL-6. Taken together, these findings indicate that the anti-inflammatory effect of exercise may be due, at least in part, to IGF-I-induced suppression of TLR4 and subsequent downregulation of the TLR4-dependent inflammatory signaling pathway.

REGULATION OF BETA-AMYLOID-STIMULATED PRO INFLAMMATORY RESPONSES VIA MITOGEN ACTIVATED PROTEIN KINASES AND REDOX SENSITIVE TRANSCRIPTION FACTORS

  • Hee, Jang-Jung;Joon, Surh-Young
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.191-191
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    • 2002
  • Inflammatory as well as oxidative tissue damage has been associated with pathophysiology of Alzheimer's disease (AD), and nonsteroidal anti-inflammatory drugs have been shown to retard the progress of AD. In this study, we have investigated the molecular mechanisms underlying oxidative and inflammatory cell death induced by beta-amyloid (Abeta), a neurotoxic peptide associated with senile plaques formed in the brains of patients with AD, in cultured PC12 cells.(omitted)

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Enhancement of the Anti-inflammatory Activities of Aralia continentalis Kitagawa Extracts Fermented by Lactobacillus plantarum (추출용액에 따른 유산균 발효 땅두릅의 항염증 효과)

  • Woo, Young Min;Kim, Ok Ju;Jo, Eun Sol;Jo, Min Young;Ahn, Mee Young;Lee, Sang-Hyeon;Ha, Jong-Myung;Kim, Andre
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1438-1447
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    • 2018
  • We investigated the anti-inflammatory activities of various organic solvent extracts with and without Lactobacillus plantarum fermentation of Aralia continentalis Kitagawa which has hypotensive effects in addition to excitatory effects on the central nervous system. It has been used to treat arthritis, colds, neuralgia, rheumatism, and itchy skin. Our extracts were tested for their anti-inflammatory potential on NO production and the expression of inflammatory factors in lipopolysaccharide-stimulated RAW264.7 macrophages. Extracts with and without L. plantarum fermentation were prepared using water, ethanol, hexane, ethyl acetate, and butanol. The RAW264.7 cells were tested for toxicity and the anti-inflammatory activity of each extract was determined at a concentration with no toxicity to the cells. The extracts used in this study significantly inhibited both the production of NO and the mRNA expression of COX-2 and iNOS, the major inflammatory factors. The production of inflammation-related cytokines $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ was also significantly reduced. These results suggest that the extracts involving fermentation by L. plantarum can inhibit cytokines by controlling the expression of inflammatory cytokine genes. It is considered that the water, ethanol, and butanol extracts after fermentation with L. plantarum could be useful as functional natural materials with anti-inflammatory effects.

The Effects of Dictamni Radicis Cortex on the iNOS Expression and Proinflammatory Cytokines Production (백선피의 iNOS발현과 염증성사이토카인의 생성에 미치는 영향)

  • Park, Jeong-Suk;Shin, Tae-Yong;Kim, Dae-Keun;Lee, Jae-Hyeok
    • Korean Journal of Pharmacognosy
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    • v.42 no.4
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    • pp.348-353
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    • 2011
  • The aim of the present study is to investigate the cytokine production inhibitory effect of a Dictamni Radicis Cortex (DRC). DRC has been commonly used as important medicinal herb in China and it used to control eczema, atopic dermatitis, fever and inflammatory diseases. Inflammation, such as a bacterial infection in vivo metabolites, such as external stimuli or internal stimuli to the defense mechanisms of the biological tissue a variety of intracellular regulatory factors deulin inflammatory TNF-${\alpha}$, IL-$1{\beta}$, IL-6, IL-8, such as proinflammatory cytokines, prostagrandin, lysosomal enzyme, free radicals are involved in a variety of mediators. The present study was designed to determine the effect of the DRC on proinflammatory factors such as NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 in lipopolysaccharide (LPS) - stimulated RAW264.7 cells. The cell toxicity was determined by MTS assay. To evaluate of anti-inflammatory effect of DRC, amount of NO was measured using the NO detection kit and the iNOS expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR). And proinflammatory cytokines were measured by ELISA kit. As a result, the DRC reduced NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 production without cytotoxicity. Our results suggest that the DRC may have an anti-inflammatory property through suppressing inflammatory mediator productions.

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.

Oxidative Stress, Chromatin Remodeling and Gene Transcription in Inflammation and Chronic Lung Diseases

  • Rahman, Irfan
    • BMB Reports
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    • v.36 no.1
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    • pp.95-109
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    • 2003
  • Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.

JS-III-49, a hydroquinone derivative, exerts anti-inflammatory activity by targeting Akt and p38

  • Yi, Young-Su;Kim, Mi-Yeon;Cho, Jae Youl
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.3
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    • pp.345-352
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    • 2017
  • Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophage-mediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) and down-regulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-$1{\beta}$ without cytotoxicity in LPS-stimulated RAW264.7 cells. JS-III-49 inhibited nuclear translocation of the $NF-{\kappa}B$ transcription factors p65 and p50 by directly targeting Akt, an upstream kinase of the $NF-{\kappa}B$ pathway, in LPS-stimulated RAW264.7 cells. However, JS-III-49 did not directly inhibit the kinase activities of Src and Syk, which are upstream kinases of Akt, in LPS-stimulated RAW264.7 cells. Moreover, JS-III-49 suppressed the nuclear translocation of c-Fos, one of the components of AP-1, by specifically targeting p38, an upstream mitogen-activated protein kinase (MAPK) in the AP-1 pathway in LPS-stimulated RAW264.7 cells. These results suggest that JS-III-49 plays an anti-inflammatory role in LPS-stimulated macrophages by targeting Akt and p38 in the $NF-{\kappa}B$ and AP-1 pathways, respectively.

Anti-Inflammatory and Antioxidative Effects of Gracilaria textorii Ethanol Extract in LPS-PG-Stimulated Human Gingival Fibroblast-1 Cells (사람 치은섬유모세포에서 잎꼬시래기 에탄올 추출물의 항염증 및 항산화 효과)

  • Park, Chungmu;Yoon, Hyunseo
    • Journal of The Korean Society of Integrative Medicine
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    • v.7 no.4
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    • pp.61-69
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    • 2019
  • Purpose : Human gingival fibroblast cell is one of the the main cell types in periodontal tissue, which they can show anti-inflammatory activity through the production of numerous lines of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukins. Porphyromonas gingivalis, one of the oral pathogens, has reported to play a critical role in the development of periodontal diseases. This study aimed to investigate anti-inflammatory and antioxidative activities of Gracilaria textorii ethanol extract (GTEE) in P. gingivalis derived lipopolysaccharide (LPS-PG) stimulated human gingival fibroblast (HGF)-1 cell line. Methods : In order to analyze anti-inflammatory and antioxidative activities of GTEE in HGF-1 cell line, NOS enzyme activity, expression levels of iNOS, COX-2, NAD(P)H quinone dehydrogenase (NQO)1 and their transcription factors were estimated by Griess reaction and western hybridization. Results : LPS-PG induced overexpression of iNOS and COX-2, which was significantly attenuated by GTEE treatment in a dose-dependent manner without any cytotoxicity. In addition, intracellular NOS activity was in accordance with the result of iNOS expression. Due to important role in the regulation of inflammatory responses, phosphorylated status of p65 and c-jun, each subunit of nuclear factor (NF)-κB and activator protein (AP)-1, was also dose-dependently ameliorated by GTEE treatment. One of phase II enzymes, NQO1, and its transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), were analyzed since elevated phase II enzyme expression inhibited inflammatory response, which was significantly elevated by GTEE treatment in HGF-1 cell line. Conclusion : In conclusion, GTEE mitigated LPS-PG-stimulated inflammatory responses by attenuating NF-κB and AP-1 activation as well as accelerating NQO1 and Nrf2 expression in HGF-1 cell line. These results indicate that GTEE might be utilized a promising strategy for potential anti-inflammatory agent in periodontal diseases.

The Acetylation-based synthesis of 3,3',4',5,5',7-hexaacetate myricetin and evaluation of its anti-inflammatory activities in lipopolysaccharide-induced RAW264.7 mouse macrophage cells

  • Kristina Lama;Hyehyun Hong;Tae-Jin Park;Jin-Soo Park;Won-Jae Chi;Seung-Young Kim
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.29-38
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    • 2023
  • Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E2, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

Effects of Combined Marine Treatment Program on Risk Factors of Metabolic Syndrome, and CRP in Elderly Musculoskeletal and Metabolic Patients (복합 해양치유 프로그램이 근골격계 및 대사성 질환자의 대사증후군 위험인자 및 CRP에 미치는 영향)

  • Kim, Hyunjun;Shin, Jaesuk
    • Journal of The Korean Society of Integrative Medicine
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    • v.8 no.1
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    • pp.37-45
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    • 2020
  • Purpose : The purpose of this study is to verify the effectiveness of combined marine healing programs by analyzing the physical composition of elderly musculoskeletal and metabolic patients, the risk factors of metabolic syndrome and the effects of the inflammatory factors, the C -reactive protein (CRP). Methods : Individuals with musculoskeletal and metabolic diseases were identified, and marine healing programs were conducted for f our hours each day for two weeks with 11 elderly participants. A one-way RM ANOVA was conducted to determine the differences due to treatment with composite marine healing systems. The results are as follows. Results : After a two-week ocean healing program, weight decreased the most, while BMI also decreased and muscle mass increased. Waist circumference, a risk factor for metabolic syndrome and CRP, decreased, and CRP demonstrated a decreasing trend. Conclusion : The above results show that the two-week marine healing program has a positive effect on the body composition and inflammatory factors of elderly musculoskeletal and metabolic patients.