• Title/Summary/Keyword: NF- κB

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Anti-inflammatory Effect of Berchemia berchemiaefolia Leaves through Inhibition of NF-κB and MAPK Signaling Activation in LPS-stimulated RAW264.7 Cells (망개나무 추출물의 NF-κB 및 MAPK 신호전달 억제를 통한 항염증 효과)

  • Kim, Da Som;Eo, Hyun Ji;Kang, Yeongyeong;Park, Gwang Hun
    • Korean Journal of Plant Resources
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    • v.34 no.1
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    • pp.31-36
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    • 2021
  • Berchemia berchemiaefolia (Makino) Koidz. is found not only in korea, but also in japan and is known as a rare plant all over the world. In this study, we evaluated anti-inflammatory effect of B. berchemiaefolia (Makino) Koidz. leaves (BBK-L) in LPS-stimulated RAW264.7 cells. BBK-L inhibited the generation of NO through the suppression of iNOS experession. BBK-L attenuated the expression of iNOS, COX-2, TNF-α, IL-1β, IL-6 induced by LPS. BBK-L decreased LPS-mediated IκB-α degradation inhibite which resulted in the inhibition of NF-κB activation in RAW264.7 cells. In addition, BBK-L suppressed ERK1/2, JNK phosphorylation induced by LPS. BBK-L showed anti-inflammatory effect through blocking the generation of the inflammatory mediators such as NO, iNOS, COX-2, TNF-α, IL-1β, IL-6 via the inhibiting of NF-κB and MAPK signaling activation. These results suggests that BBK-L may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

Inhibitory Effect of Inflammatory Cytokines Secretion of Cheonggeumganghwa-tang in Mast cell (비만세포에서의 청금강화탕의 염증성 세포활성물질 분비 억제 효과)

  • Choi Young Soo;Moon Goo;Kim Dong Woung;Han Se Hee;Won Jin Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.3
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    • pp.887-892
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    • 2004
  • Cheonggeumganghwa-tang(CGT) has been used for the purpose of prevention and treatment of bronchial asthma and allergic asthma in Korea. To investigate the biological effect of CGT, the author examined cytotoxicity and inflammatory cytokines secretion with human mast cell line, HMC-1. HMC-1 was stimulated with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. CGT by itself had no effect on viability of HMC-1. The effects of CGT on the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 from HMC-1 were evaluated with enzyme-linked immunosorbent assay (ELISA). CGT (1 ㎎/㎖) inhibited PMA plus A23187 -induced TNF-α and IL-6 secretion, by 93.86 ± 2.05%, 68.69 ± 2.86%, respectively. CGT also inhibited the NF-κB (p50) expression. Taken together, these results suggest that CGT inhibit the production of inflammatory cytokines in HMC-1 cells through blockade of NF-κB activation.

Tubeimoside-1 suppresses breast cancer metastasis through downregulation of CXCR4 chemokine receptor expression

  • Peng, Yaojin;Zhong, Yan;Li, Gao
    • BMB Reports
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    • v.49 no.9
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    • pp.502-507
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    • 2016
  • To examine the effect of TBMS1on breast cancer metastasis, and investigate the potential mechanism by which Tubeimoside-1 (TBMS1) inhibits the CXCR4 expression in breast cancer cells. The expression of CXCR4 in breast cancer cell lines was determined by immunoblotting and real-time PCR. The effect of TBMS1 on NF-κB binding activity was evaluated by EMSA assay and ChIP analysis. Cell proliferation and invasion were analyzed by MTT assay and transwell invasion assay, respectively. The effect of TBMS1 on breast cancer metastasis was further evaluated in a metastasis model of nude mice. TBMS1 suppressed the expression of CXCR4 through inhibition of NF-κB binding activity. TBMS1 inhibited CXCL12-induced invasion in breast cancer cells, while ectopic expression of CXCR4 abolished the inhibitive activity of TBMS1. TBMS1 suppressed breast cancer metastasis in the metastatic model of nude mice. TBMS1 suppressed the CXCR4-mediated metastasis of breast cancer by inhibiting NF-κB binding activity.

Neogambogic acid relieves myocardial injury induced by sepsis via p38 MAPK/NF-κB pathway

  • Fu, Wei;Fang, Xiaowei;Wu, Lidong;Hu, Weijuan;Yang, Tao
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.6
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    • pp.511-518
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    • 2022
  • Sepsis-associated myocardial injury, an invertible myocardial depression, is a common complication of sepsis. Neogambogic acid is an active compound in garcinia and exerts anthelmintic, anti-inflammatory, and detoxification properties. The role of neogambogic acid in sepsis-associated myocardial injury was assessed. Firstly, mice were pretreated with neogambogic acid and then subjected to lipopolysaccharide treatment to induce sepsis. Results showed that lipopolysaccharide treatment induced up-regulation of biomarkers involved in cardiac injury, including lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and troponin I (cTnI). However, pretreatment with neogambogic acid reduced levels of LDH, CK-MB, and cTnI, and ameliorated histopathological changes in the heart tissues of septic mice. Secondly, neogambogic acid also improved cardiac function in septic mice through reduction in left ventricular end-diastolic pressure, and enhancement of ejection fraction, fractional shortening, and left ventricular systolic mean pressure. Moreover, neogambogic acid suppressed cardiac apoptosis and inflammation in septic mice and reduced cardiac fibrosis. Lastly, protein expression of p-p38, p-JNK, and p-NF-κB in septic mice was decreased by neogambogic acid. In conclusion, neogambogic acid exerted anti-apoptotic, anti-fibrotic, and anti-inflammatory effects in septic mice through the inactivation of MAPK/NF-κB pathway.

Anti-inflammatory Effects of Rumohra adiantiformis Extracts Fermented with Bovista plumbea Mycelium in LPS-stimulated RAW 264.7 Cells (LPS로 자극된 RAW 264.7 세포에서 찹쌀떡버섯 균사체로 생물전환된 루모라고사리 추출물의 항염증 효과)

  • Ji-Hye Hong;Eun-Seo Jang;Myung-Chul Gil;Gye Won Lee;Young Ho Cho
    • Journal of Life Science
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    • v.33 no.6
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    • pp.471-480
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    • 2023
  • This study was designed to evaluate the anti-inflammatory effects of Rumohra adiantiformis extracts fermented with Bovista plumbea mycelium (B-RAE) in LPS-stimulated RAW 264.7 cells. The total polyphenol and total flavonoid content of B-RAE were 379.26±7.77 mg/g and 50.85±3.08 mg/g, respectively. The results of measuring the antioxidant activity of B-RAE showed that it scavenges 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and superoxide anion radical in a dose-dependent manner. B-RAE inhibited nitric oxide (NO) production in a dose-dependent manner without affecting cell viability. The gene expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-lβ (IL-1β), and IL-6 was measured using real time quantitative reverse transcription PCR (qRT-PCR). We found that, compared to the LPS-treated group, B-RAE significantly reduced the mRNA levels of the pro-inflammatory cytokines in a concentration-dependent manner. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the phosphorylation of transcription factors such as nuclear factor-κB (NF-κB), and the mitogen-activated protein kinase (MAPK) signaling pathway proteins were assessed using Western blot analysis. We found that B-RAE significantly suppressed the expression of iNOS and COX-2, but their expression was increased by LPS treatment. In addition, the phosphorylation of NF-κB and IκB, which was increased by LPS treatment, was reduced with B-RAE treatment. The effect of B-RAE on the phosphorylation of the MAPK signaling pathway proteins was measured, and the phosphorylation of extracellular signal-regulated kinase (ERK) and the p38 MAPK proteins decreased in a dose-dependent manner, while the phosphorylation of c-Jun N-terminal kinase (JNK) increased. These anti-inflammatory effects of B-RAE may thus have been achieved through the high antioxidant activity, the inhibition of NO production through the suppression of iNOS and COX-2 expression, the inhibition of the NF-κB pathway, and the suppression of pro-inflammatory cytokine expression.

Anti-Inflammatory Properties of Aloe-Emodin in Adipocytes through a TLR4/NF-κB/ERK Signaling Pathway (지방세포에서 TLR4/NF-κB/ERK 신호조절을 통한 Aloe-Emodin의 염증 억제 효과)

  • Park, Mi-Young
    • The Korean Journal of Food And Nutrition
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    • v.30 no.2
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    • pp.312-318
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    • 2017
  • Aloe-emodin (AE) is the major bioactive component in aloe and known to exhibit anti-inflammatory activities. However, it has not been elucidated whether its anti-inflammatory potency can contribute to the elimination of obesity. The aim of the current study is to investigate the effect of AE on toll-like receptor 4 (TLR4) pathways in the presence of lipopolysaccharide (LPS) in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with AE ($0-20{\mu}M$) for one hour, followed by LPS treatment for 30 min and then, adipokine mRNA expression levels were measured. Next, TLR4-related molecules were measured in LPS-stimulated 3T3-L1 adipocytes. AE significantly decreased the mRNA expression of the tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in a dose-dependent manner. Moreover, AE suppressed TLR4 mRNA expression. Further study showed that AE could suppress the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) and phosphorylation of extracellular receptor-activated kinase (pERK). The results of this study suggest that AE directly inhibits $TLR4/NF-{\kappa}B/ERK$ signaling pathways and decreases the inflammatory response in adipocytes.

Aqueous extract of Jigal-san ameliorates acute inflammatory responses in RAW 264.7 cells and rats (NF-𝜅B 및 MAPK억제를 통한 지갈산(止渴散) 물추출물의 염증억제효과)

  • Jeong, Deok Ja;Park, Sang Mi;Kim, Sang Chan
    • Herbal Formula Science
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    • v.29 no.4
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    • pp.205-227
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    • 2021
  • Objectives : Jigal-san (JGS, 止渴散) has been used in East Asia including Korea, Japan and China for the treatment of breast inflammatory disorders and severe thirst. JGS originated from Euimunpalbeob (醫門八法; Yimenbafa) composed of Lonicerae Flos and Taraxaci Herba. According to previous studies Lonicerae Flos and Taraxaci Herba have an anti-inflammatory effect, respectively. But, there is no studies regarding on the effects of JGS in the immunological activities. The present study evaluated the anti-inflammatory effects of JGS in vitro and in vivo. Methods : Cell viability was evaluated by MTT assay, and NO was evaluated by content of the nitrite content in culture medium. TNF-α, IL-1β and IL-6 were quantified by ELISA. The protein expression of NF-κB, MAPKs, and iNOS were assessed by western blot analysis. Furthermore, the effects of JGS on acute inflammation were observed in rat paw edema model. Results : The JGS ameliorates the LPS-activated changes in the protein expression of NF-κB, p-JNK, and iNOS, as well as the production of NO and pro-inflammatory cytokines. In rat paw edema study, administration of 0.3 and 1.0 g/kg of JGS for 4 consecutive days inhibited the carrageenan (CA)-induced increases of edema and iNOS expression. Conclusions : These results demonstrate that JGS has anti-inflammatory effect in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, via suppression of the NF-κB and MAPK pathways (JNK, not p-38 and ERK). In addition, the results of the CA-induced paw edema indicate that JGS ameliorates an inflammatory edema. Therefore, the present study could provide scientific evidence for the anti-inflammatory effect of JGS as well as the underlying mechanisms.

The Effect of Acanthopanax sessiliflorum Cheonghyeol Plus on NF-κB and MAPKs Signaling and Vascular Attachment Factors (오가피청혈플러스가 NF-κB 및 MAPKs 신호전달체계와 혈관부착인자 등에 미치는 영향)

  • Lee, Ji-won;Choi, Gyu-cheol;Bae, Ji-eun;Yoo, Ho-ryong;Kim, Yoon-sik;Seol, In-chan
    • The Journal of Internal Korean Medicine
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    • v.41 no.6
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    • pp.967-983
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    • 2020
  • Objective: This study was performed to investigate the effect of Acanthopanax sessiliflorum Cheonghyeol plus (ASCP) on NF-κB and MAPK signaling and vascular adhesion factors associated with dyslipidemia in human umbilical vein endothelial cells (HUVECs). Methods: We measured the scavenging activity of DPPH radical and ABTS radical by ASCP in HUVECs. We measured the protein expression levels of NF-κB, IκBα, ERK, JNK, and p38 after treatment of HUVECs with TNF-α. We measured the expression levels of MCP-1, ICAM-1, and VCAM-1 mRNA and of MCP-1, ICAM-1, and VCAM-1 biomarkers after treatment of HUVECs with TNF-α. Results: The DPPH and ABTS radical scavenging activity of ASCP increased in a concentration-dependent manner. NF-κB, IκB, ERK, p38 protein expression levels decreased following ASCP treatment at all concentrations compared to untreated control HUVECs. JNK protein expression levels decreased in ASCP-treated HUVECs compared to untreated controls at concentrations of 100 ㎍/mL. MCP-1 mRNA expression level decreased with ASCP treatment ≥200 ㎍/mL compared to the control. ICAM-1 and VCAM-1 mRNA expression levels decreased at all concentrations compared to the control. MCP-1 protein expression level was reduced compared to the control at concentrations ≥200 ㎍/mL, ICAM-1 protein expression level was reduced compared to the control at concentrations ≥100 ㎍/mL, and VCAM-1 protein expression level was reduced at all concentrations. Conclusions: These results suggest that ASCP has an antioxidative and hypolipidemic effect and that ASCP could treat and prevent dyslipidemia, atherosclerosis, and cardio-cerebrovascular diseases.

The role of discoid domain receptor 1 on renal tubular epithelial pyroptosis in diabetic nephropathy

  • Zhao, Weichen;He, Chunyuan;Jiang, Junjie;Zhao, Zongbiao;Yuan, Hongzhong;Wang, Facai;Shen, Bingxiang
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.6
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    • pp.427-438
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    • 2022
  • Pyroptosis, a form of cell death associated with inflammation, is known to be involved in diabetic nephropathy (DN), and discoid domain receptor 1 (DDR1), an inflammatory regulatory protein, is reported to be associated with diabetes. However, the mechanism underlying DDR1 regulation and pyroptosis in DN remains unknown. We aimed to investigate the effect of DDR1 on renal tubular epithelial cell pyroptosis and the mechanism underlying DN. In this study, we used high glucose (HG)-treated HK-2 cells and rats with a single intraperitoneal injection of streptozotocin as DN models. Subsequently, the expression of pyroptosis-related proteins (cleaved caspase-1, GSDMD-N, Interleukin-1β [IL-1β], and interleukin-18 [IL-18]), DDR1, phosphorylated NF-κB (p-NF-κB), and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes were determined through Western blotting. IL-1β and IL-18 levels were determined using ELISA. The rate of pyroptosis was assessed by propidium iodide (PI) staining. The results revealed upregulated expression of pyroptosisrelated proteins and increased concentration of IL-1β and IL-18, accompanied by DDR1, p-NF-κB, and NLRP3 upregulation in DN rat kidney tissues and HG-treated HK-2 cells. Moreover, DDR1 knockdown in the background of HG treatment resulted in inhibited expression of pyroptosis-related proteins and attenuation of IL-1β and IL-18 production and PI-positive cell frequency via the NF-κB/NLRP3 pathway in HK-2 cells. However, NLRP3 overexpression reversed the effect of DDR1 knockdown on pyroptosis. In conclusion, we demonstrated that DDR1 may be associated with pyroptosis, and DDR1 knockdown inhibited HG-induced renal tubular epithelial cell pyroptosis. The NF-κB/NLRP3 pathway is probably involved in the underlying mechanism of these findings.

Regulation of the Immune System by NF-κB and IκB

  • Liou, Hsiou-Chi
    • BMB Reports
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    • v.35 no.6
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    • pp.537-546
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    • 2002
  • NF-${\kappa}B$/Rel transcription factor family participates in diverse biological processes including embryo development, hematopoiesis, immune regulation, as well as neuronal functions. In this review, the NF-${\kappa}B$/Rel signal transduction pathways and their important roles in the regulation of immune system will be discussed. NF-${\kappa}B$/Rel members execute distinct functions in multiple immune cell types via the regulation of target genes essential for cell proliferation, survival, effector functions, cell trafficking and communication, as well as the formation of lymphoid architecture. Consequently, proper activation of NF-${\kappa}B$/Rel during immune responses to allergens, auto-antigens, allo-antigens, and pathogenic infection is crucial for the integrity of host innate and adaptive immunity.