ERK1- and TBK1-targeted anti-inflammatory activity of an ethanol extract of Dryopteris crassirhizoma

Yang, Yanyan; Lee, Gang Jun; Yoon, Deok Hyo; Yu, Tao; Oh, Joo Hyun; Jeong, Deok; Lee, Jongsung; Kim, Seong Hwan; Kim, Tae‐Woong; Cho, Jae Youl

doi:10.1016/j.jep.2012.11.019

Cited by 36 publications

(23 citation statements)

References 49 publications

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“…4). Interestingly, other herbal plants such as Dryopteris crassirhizoma also exhibited IRF3-targeted anti-inflammatory activities through the suppression of TBK1 [20], [57]. Our data strongly imply that suppression of the TBK1/IRF3 pathway could, in part, contribute to the immunopharmacological activity of BIOGF1K.…”

Section: Discussionmentioning

confidence: 59%

In vitro antioxidative and anti-inflammatory effects of the compound K-rich fraction BIOGF1K, prepared from Panax ginseng

Hossen

Hong

Baek

et al. 2017

Journal of Ginseng Research

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BackgroundBIOGF1K, a compound K-rich fraction prepared from the root of Panax ginseng, is widely used for cosmetic purposes in Korea. We investigated the functional mechanisms of the anti-inflammatory and antioxidative activities of BIOGF1K by discovering target enzymes through various molecular studies.MethodsWe explored the inhibitory mechanisms of BIOGF1K using lipopolysaccharide-mediated inflammatory responses, reporter gene assays involving overexpression of toll-like receptor adaptor molecules, and immunoblotting analysis. We used the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to measure the antioxidative activity. We cotransfected adaptor molecules, including the myeloid differentiation primary response gene 88 (MyD88) and Toll/interleukin-receptor domain containing adaptor molecule-inducing interferon-β (TRIF), to measure the activation of nuclear factor (NF)-κB and interferon regulatory factor 3 (IRF3).ResultsBIOGF1K suppressed lipopolysaccharide-triggered NO release in macrophages as well as DPPH-induced electron-donating activity. It also blocked lipopolysaccharide-induced mRNA levels of interferon-β and inducible nitric oxide synthase. Moreover, BIOGF1K diminished the translocation and activation of IRF3 and NF-κB (p50 and p65). This extract inhibited the upregulation of NF-κB-linked luciferase activity provoked by phorbal-12-myristate-13 acetate as well as MyD88, TRIF, and inhibitor of κB (IκBα) kinase (IKKβ), and IRF3-mediated luciferase activity induced by TRIF and TANK-binding kinase 1 (TBK1). Finally, BIOGF1K downregulated the NF-κB pathway by blocking IKKβ and the IRF3 pathway by inhibiting TBK1, according to reporter gene assays, immunoblotting analysis, and an AKT/IKKβ/TBK1 overexpression strategy.ConclusionOverall, our data suggest that the suppression of IKKβ and TBK1, which mediate transcriptional regulation of NF-κB and IRF3, respectively, may contribute to the broad-spectrum inhibitory activity of BIOGF1K.

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Section: Discussionmentioning

confidence: 59%

In vitro antioxidative and anti-inflammatory effects of the compound K-rich fraction BIOGF1K, prepared from Panax ginseng

Hossen

Hong

Baek

et al. 2017

Journal of Ginseng Research

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“…In particular, TBK1 is known to be an important enzyme regulating virus-induced inflammatory symptoms [25]. Our recent study found that inhibitory plant extract (ethanol extract of Dryopteris crassirhizoma ) on this enzyme is able to display curative activity against gastritis symptoms stimulated by HCl/EtOH [26]. In case of p38, it was reported that this enzyme is critical in managing various inflammatory diseases such as asthma and inflammatory bowel disease [27], [28].…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2

Yang

Kwak

et al. 2017

Journal of Ginseng Research

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BackgroundGinsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects.MethodsThe in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis factor-α/interferon-γ-treated synovial cells, and HEK293 cells transfected with various inducers of inflammation.ResultsG-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis factor-α and interleukin-1β. G-Rc also markedly suppressed the activation of TANK-binding kinase 1/IκB kinase ε/interferon regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells.ConclusionG-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase 1/IκB kinase ε/interferon regulatory factor-3 and p38/ATF-2 signaling.

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“…TBK1 is involved in regulating rheumatoid synovitis by controlling TLR3-mediated activation of IRF7 and subsequent transcription of the IP-10 gene, which is closely related to the pathogenesis of rheumatoid arthritis [25]. TBK1 also acts as a key regulator in neuroinflammation, microvascular inflammation and gastritis [26][27][28]. Interestingly, TBK1 contributes to obesity regulation through the repression of energy expenditure.…”

Section: Potential Clinical Applications Of Tbk1 Inhibitorsmentioning

confidence: 99%

TBK1 inhibitors: a review of patent literature (2011 – 2014)

Yang

Yin

et al. 2015

Expert Opinion on Therapeutic Patents

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The role of TBK1 in various diseases has prompted the further investigation of significant targets. Although research on TBK1 inhibitors has increased over the last few years, only a few inhibitors of this kinase have been identified. In addition, almost all of the chemical inhibitors are modified from different scaffolds and/or chemotypes of pyrimidine. Specifically, compound BX795 is the representative one, which was first patented as a potent TBK1 inhibitor. Even though some compounds have displayed interesting potential inhibition and selectivity of TBK1 in vitro and in in vivo trials, the development of more efficient and selective TBK1 inhibitors is still required.

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ERK1- and TBK1-targeted anti-inflammatory activity of an ethanol extract of Dryopteris crassirhizoma

Cited by 36 publications

References 49 publications

In vitro antioxidative and anti-inflammatory effects of the compound K-rich fraction BIOGF1K, prepared from Panax ginseng

In vitro antioxidative and anti-inflammatory effects of the compound K-rich fraction BIOGF1K, prepared from Panax ginseng

Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2

TBK1 inhibitors: a review of patent literature (2011 – 2014)

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