Syk/Src-targeted anti-inflammatory activity of Codariocalyx motorius ethanolic extract

Kim, Eunji; Yoon, Kee Dong; Lee, Woo-Shin; Yang, Woo Seok; Kim, Shi Hyoung; Sung, Nak Yoon; Baek, Ki Hyun; Kim, Yong; Htwe, Khin Myo; Kim, Young Dong; Hong, Sungyoul; Kim, Jong-Hoon; Cho, Jae Youl

doi:10.1016/j.jep.2014.05.013

Cited by 16 publications

(10 citation statements)

References 39 publications

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“…Cc-ME also exerted an anti-inflammatory activity in a gastritis mouse model by dramatically ameliorating the ulcerative lesions in the stomachs of gastritis mice and by decreasing the mRNA expression of inflammatory genes (Figures 4(b) and 4(c) ). It is reasonable to think that this in vivo anti-inflammatory activity of Cc-ME is mediated by the luteolin, quercetin, and kaempferol contained in Cc-ME because those compounds have already been observed to show anti-inflammatory effects that ameliorate the morphological finding of peritonitis and gastritis [ 33 , 49 – 53 ]. Taken together, these results strongly indicate that Cc-ME has an in vivo anti-inflammatory activity that can ameliorate the morphological finding of inflammatory diseases and also suggest that the flavonoids in Cc-ME might be the main components of its in vivo anti-inflammatory effect.…”

Section: Discussionmentioning

confidence: 99%

Src Is a Prime Target Inhibited by Celtis choseniana Methanol Extract in Its Anti‐Inflammatory Action

Kim

Choi

Lee

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Celtis choseniana is the traditional plant used at Korea as a herbal medicine to ameliorate inflammatory responses. Although Celtis choseniana has been traditionally used as a herbal medicine at Korea, no systemic research has been conducted on its anti-inflammatory activity. Therefore, the present study explored an anti-inflammatory effect and its underlying molecular mechanism using Celtis choseniana methanol extract (Cc-ME) in macrophage-mediated inflammatory responses. In vitro anti-inflammatory activity of Cc-ME was evaluated using RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS), pam3CSK4 (Pam3), or poly(I:C). In vivo anti-inflammatory activity of Cc-ME was investigated using acute inflammatory disease mouse models, such as LPS-induced peritonitis and HCl/EtOH-induced gastritis. The molecular mechanism of Cc-ME-mediated anti-inflammatory activity was examined by Western blot analysis and immunoprecipitation using whole cell and nuclear fraction prepared from the LPS-stimulated RAW264.7 cells and HEK293 cells. Cc-ME inhibited NO production and mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and tumor necrosis factor-alpha (TNF-α) in the RAW264.7 cells and peritoneal macrophages induced by LPS, pam3, or poly(I:C) without cytotoxicity. High-performance liquid chromatography (HPLC) analysis showed that Cc-ME contained anti-inflammatory flavonoids quercetin, luteolin, and kaempferol. Among those, the content of luteolin, which showed an inhibitory effect on NO production, was highest. Cc-ME suppressed the NF-κB signaling pathway by targeting Src and interrupting molecular interactions between Src and p85, its downstream kinase. Moreover, Cc-ME ameliorated the morphological finding of peritonitis and gastritis in the mouse disease models. Therefore, these results suggest that Cc-ME exerted in vitro and in vivo anti-inflammatory activity in LPS-stimulated macrophages and mouse models of acute inflammatory diseases. This anti-inflammatory activity of Cc-ME was dominantly mediated by targeting Src in NF-κB signaling pathway during macrophage-mediated inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

Src Is a Prime Target Inhibited by Celtis choseniana Methanol Extract in Its Anti‐Inflammatory Action

Kim

Choi

Lee

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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“…Pharmacologically effective plant extracts traditionally used to treat diseases share phytochemicals. Luteolin-7-O-glucuronide (L7Gn, Figure 1) is a phytochemical common to various anti-inflammatory plant extracts, including those of Perilla frutescens, Remirea maritima, Codariocalyx motorius, and Ixeris dentata [13][14][15][16]. Recently, L7Gn was identified as the major constituent of Cirsium japonicum CJ-50 fractions responsible for its anti-inflammatory effects in macrophages, elucidated to inhibit c-Jun N-terminal kinase (JNK) for its anti-inflammatory effects [17].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory and Anti-Oxidative Effects of luteolin-7-O-glucuronide in LPS-Stimulated Murine Macrophages through TAK1 Inhibition and Nrf2 Activation

Cho

Park

Cho

2020

IJMS

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Various herbal extracts containing luteolin-7-O-glucuronide (L7Gn) have been traditionally used to treat inflammatory diseases. However, systemic studies aimed at elucidating the anti-inflammatory and anti-oxidative mechanisms of L7Gn in macrophages are insufficient. Herein, the anti-inflammatory and anti-oxidative effects of L7Gn and their underlying mechanisms of action in macrophages were explored. L7Gn inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by transcriptional regulation of inducible NO synthase (iNOS) in a dose-dependent manner. The mRNA expression of inflammatory mediators, including cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), was inhibited by L7Gn treatment. This suppression was mediated through transforming growth factor beta-activated kinase 1 (TAK1) inhibition that leads to reduced activation of nuclear factor-κB (NF-κB), p38, and c-Jun N-terminal kinase (JNK). L7Gn also enhanced the radical scavenging effect and increased the expression of anti-oxidative regulators, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1), by nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) activation. These results indicate that L7Gn exhibits anti-inflammatory and anti-oxidative properties in LPS-stimulated murine macrophages, suggesting that L7Gn may be a suitable candidate to treat severe inflammation and oxidative stress.

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“…1A ) is the active component of Erigeron breviscapus , Clerodendrum phlomidis and Oroxylum indicum Vent and is used to treat inflammation, diabetes, nervous disorders, asthma, rheumatism, digestive disorders, and urinary disorders; it is also given as a bitter tonic [ 10 11 ]. In addition, Codariocalyx motorius with structural analogue of SCT (SCT-6-O-glucuronide) was also shown to suppress LPS-induced inflammatory responses in macrophages and a HCl/EtOH-triggered gastritis symptoms [ 12 ]. From a pharmacological perspective, SCT has been reported to exert antioxidative, anti-cancer, and neuroprotective activities [ 13 14 ].…”

Section: Introductionmentioning

confidence: 99%

Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity

Sung

Kim

Cho

2015

Korean J Physiol Pharmacol

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Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-κB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-β (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-κ B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-κB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-κB activation.

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Syk/Src-targeted anti-inflammatory activity of Codariocalyx motorius ethanolic extract

Cited by 16 publications

References 39 publications

Src Is a Prime Target Inhibited by Celtis choseniana Methanol Extract in Its Anti‐Inflammatory Action

Src Is a Prime Target Inhibited by Celtis choseniana Methanol Extract in Its Anti‐Inflammatory Action

Anti-Inflammatory and Anti-Oxidative Effects of luteolin-7-O-glucuronide in LPS-Stimulated Murine Macrophages through TAK1 Inhibition and Nrf2 Activation

Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity

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