Fab Fragment of Immunoglobulin Y Modulates NF-κB and MAPK Signaling through TLR4 and αVβ3 Integrin and Inhibits the Inflammatory Effect on R264.7 Macrophages

Author(s):  
Xin Zhou ◽  
Dong Uk Ahn ◽  
Minquan Xia ◽  
Qi Zeng ◽  
Xiaomeng Li ◽  
...  
2018 ◽  
Vol 19 (7) ◽  
pp. 2027 ◽  
Author(s):  
Jingyu He ◽  
Xianyuan Lu ◽  
Ting Wei ◽  
Yaqian Dong ◽  
Zheng Cai ◽  
...  

Hedyotis diffusa is a folk herb that is used for treating inflammation-related diseases in Asia. Previous studies have found that iridoids in H. diffusa play an important role in its anti-inflammatory activity. This study aimed to investigate the anti-inflammatory effect and potential mechanism of five iridoids (asperuloside (ASP), asperulosidic acid (ASPA), desacetyl asperulosidic acid (DAA), scandoside methyl ester (SME), and E-6-O-p-coumaroyl scandoside methyl ester (CSME)) that are presented in H. diffusa using lipopolysaccharide (LPS)—induced RAW 264.7 cells. ASP and ASPA significantly decreased the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in parallel with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. ASP treatment suppressed the phosphorylation of the inhibitors of nuclear factor-kappaB alpha (IκB-α), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The inhibitory effect of ASPA was similar to that of ASP, except for p38 phosphorylation. In summary, the anti-inflammatory effects of ASP and ASPA are related to the inhibition of inflammatory cytokines and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, which provides scientific evidence for the potential application of H. diffusa.


2018 ◽  
Vol 43 (4) ◽  
pp. 375-384 ◽  
Author(s):  
Chang-Gu Hyun ◽  
Min-Jin Kim ◽  
Sang Suk Kim ◽  
Ji Hye Ko ◽  
Young Il Moon ◽  
...  

Abstract Objective In this study, we evaluated the anti-inflammatory effect of Shiranuhi flower in RAW 264.7 cells. Methods The effects of the extracts and solvent fractions on cell viability and LPS-induced inflammatory responses were investigated in RAW 264.7 cells. Results The results showed that the ethyl acetate fraction (HEF) significantly decreased NO production in RAW 264.7 cells; however, cell viability was not affected. In addition, ELISA assay revealed that HEF significantly inhibited the productions of PGE2, TNF-α, and IL-6. As well, using Western blot analysis, it was observed that HEF significantly reduced the expression levels of iNOS and COX-2 in a dose dependent manner. Furthermore, we detected a reduced phosphorylation of mitogen-activated protein kinases such as p38, JNK, and ERK1/2. This indicates that HEF regulates LPS-induced inflammatory responses, at least in part, via suppressing the MAPK signaling pathway. Correlation analysis also showed that anti-inflammatory activities were highly correlated to antioxidant activities in this study. Characterization of the Shiranuhi flowers for flavonoid contents using HPLC showed varied quantity of narirutin and hesperidin. Conclusion Overall, the results demonstrate that HEF may be a potential anti-inflammatory agent. In addition, our findings contribute to understanding the molecular mechanism underlying the anti-inflammatory effect of Shiranuhi flower.


Author(s):  
Jingyu He ◽  
Jiafeng Li ◽  
Han Liu ◽  
Zichao Yang ◽  
Fenghua Zhou ◽  
...  

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.


Author(s):  
Eun Suk Son ◽  
Jeong-Wooung Park ◽  
Hye Ran Park ◽  
Woorijarang Han ◽  
Dae Eun Yun ◽  
...  

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.


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