Src/NF-κB-targeted inhibition of LPS-induced macrophage activation and dextran sodium sulphate-induced colitis by Archidendron clypearia methanol extract

Yang, Woo Seok; Lee, Jaehwi; Kim, Tae‐Woong; Kim, Ji Hye; Lee, Sukchan; Rhee, Man Hee; Hong, Sungyoul; Cho, Jae Youl

doi:10.1016/j.jep.2012.04.026

Cited by 42 publications

(16 citation statements)

References 31 publications

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“…Growing evidence indicated that the inhibition of NF- κ B activity (e.g., a direct blockade of RelA (p65), suppression of I κ B α degradation, or IKK β activity) may alleviate the severity of intestinal inflammation [5]. Numerous natural anti-inflammatory products (e.g., Cissus quadrangularis , Taraxacum officinale , and Sanguisorba officinalis ) [32, 33] have been reported as NF- κ B inhibitors, which can be regarded as potential anti-inflammatory drug candidates. Indeed, many recent studies have focused on developing novel anti-inflammatory drugs targeted to regulate NF- κ B activity [34].…”

Section: Discussionmentioning

confidence: 99%

Ethanol Extract ofAntrodia camphorataGrown on Germinated Brown Rice Suppresses Inflammatory Responses in Mice with Acute DSS-Induced Colitis

Park

2013

Evidence-Based Complementary and Alternative Medicine

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The anti-inflammatory activity of Antrodia camphorata (AC) grown on germinated brown rice (CBR) extract was evaluated in vitro and in vivo. CBR suppressed the release of nitric oxide (NO) and prostaglandin (PG) E2 from lipopolysaccharide-(LPS-)stimulated RAW264.7 cells. CBR inhibited the level of inducible nitric oxide synthase (iNOS) and cyclooxygenase-(COX-)2 proteins, and it activated p38-MAPK, extracellular signal-related kinases (ERK), and NF-κB in LPS-stimulated RAW264.7 macrophages. LPS-induced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA expression was reduced in CBR-treated RAW264.7 cells. In concert with in vitro data, CBR suppressed the levels of dextran-sulfate-sodium-(DSS-)induced iNOS and COX-2 proteins in the colon tissue. CBR treatment inhibited activated p38-MAPK, ERK, and NF-κB proteins in the colon tissue of DSS-induced mice. TNF-α and IL-6 mRNA expression was reduced in DSS+CBR-treated mice. The disease activity index and histological scores were significantly lower in CBR-treated mice (500 mg/kg/day) than in DSS-treated mice (P < 0.05 versus DSS). This is the first report of anti-inflammatory activity of CBR in DSS-induced acute colitis. These results suggest that CBR is a promising, potential agent for preventing acute colitis through the inhibition of NF-κB signaling and its upstream signaling molecules, including MAPKs.

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Section: Discussionmentioning

confidence: 99%

Ethanol Extract ofAntrodia camphorataGrown on Germinated Brown Rice Suppresses Inflammatory Responses in Mice with Acute DSS-Induced Colitis

Park

2013

Evidence-Based Complementary and Alternative Medicine

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“…The ethanol extract of Artemisia asiatica , the methanol extract of Cerbera manghas, and the methanol extract of Hopea odorata also suppress the production of NO, PGE 2 , and TNF- α in LPS-stimulated macrophages and ameliorate the symptoms of EtOH/HCl-induced gastritis [85–87]. The methanol extract of Archidendron clypearia suppresses the production of NO, PGE 2 , and TNF- α in LPS-stimulated macrophages and ameliorates the symptoms of dextran sodium sulfate (DSS)-induced colitis [82]. The ethanol extract of Myrsine seguinii also suppresses the production of NO, PGE2, and TNF- α in LPS-stimulated macrophages and ameliorates the symptoms of thioglycollate-induced peritonitis [88].…”

Section: Functions Of Syk In Macrophage-mediated Inflammatory Respmentioning

confidence: 99%

Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

Son

Ryou

et al. 2014

Mediators of Inflammation

152

175

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Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases.

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“…However, the mechanism leading to degradation of IκBα involves complicate intracellular signaling pathways under LPS-stimulated macrophages. Syk and Src kinases are also found to be involved in this mechanism and are responsible for their early activation (Yang et al ., 2012). Whole cell lysate immunoblot analysis exhibited that LPS-induced IκBα phosphorylation at 5, 15, and 30 min were inhibited by the presence of PPP (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Activated TAK1 interacts with the evolutionarily conserved signaling intermediate in toll pathway (ECSIT) protein to initiate NF-κB and AP-1 signaling cascades, through phosphorylation of IKK and MKKs, respectively (Akira and Takeda, 2004). Alternatively, MyD88 adaptor proteins are linked to Syk and Src kinase activation, which leads to TAK1-independent activation of NF-κB through p85 and AKT phosphorylation (Yang et al ., 2012). …”

Section: Introductionmentioning

confidence: 99%

Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

Yang

Kim

Jeong

et al. 2016

Biomolecules & Therapeutics

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(E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to β-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-κB activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-α (TNF-α) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-κB-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-κB and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

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Src/NF-κB-targeted inhibition of LPS-induced macrophage activation and dextran sodium sulphate-induced colitis by Archidendron clypearia methanol extract

Cited by 42 publications

References 31 publications

Ethanol Extract ofAntrodia camphorataGrown on Germinated Brown Rice Suppresses Inflammatory Responses in Mice with Acute DSS-Induced Colitis

Ethanol Extract ofAntrodia camphorataGrown on Germinated Brown Rice Suppresses Inflammatory Responses in Mice with Acute DSS-Induced Colitis

Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

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