Antiinflammatory Activities of Crebanine by Inhibition of NF-κB and AP-1 Activation through Suppressing MAPKs and Akt Signaling in LPS-Induced RAW264.7 Macrophages

Intayoung, Pichanan; Limtrakul, Pornngarm; Yodkeeree, Supachai

doi:10.1248/bpb.b15-00479

Cited by 55 publications

(41 citation statements)

References 45 publications

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“…Moreover, MAPKs have been involved in pro-inflammatory signaling cascades and large numbers of evidence has demonstrated that the activation of ERK1/2 and JNK is involved in up-regulation of nitric oxide and pro-inflammatory cytokines in LPS- induced macrophages [37, 38]. Thus, we assessed that 4'- O -Demethylophiopogonanone E inhibited the inflammatory response via blocking the phosphorylation of MAPKs in LPS-stimulated macrophages.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of anti-inflammatory activity of compounds isolated from the rhizome of Ophiopogon japonicas

Zhao

Chen

Deng³

et al. 2017

BMC Complement Altern Med

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Background Ophiopogon japonicas (L.f) Ker-Gawl has been used as a traditional Chinese medicine to cure acute and chronic inflammation and cardiovascular diseases including thrombotic diseases for thousands of years. Previous phytochemical studies showed that O. japonicus contained compounds with anti-inflammatory activity. The aim of this study was to identify and isolate compounds with anti-inflammatory activity from the rhizome of O. japonicas.MethodsCompounds were isolated by various column chromatography and their structures were identified in terms of nuclear magnetic resonance spectrum (NMR) and mass spectrum (MS). To measure the anti-inflammatory effects of thirteen compounds in LPS-induced RAW 264.7 macrophage cells, we used the following methods: cell viability assay, nitric oxide assay, enzyme-linked immunosorbent assay, quantitative real-time PCR analysis and western blotting analysis.ResultsOne new and twelve known compounds (mainly homoisoflavonoids) were extracted from O. japonicas, in which 4′-O-Demethylophiopogonanone E (10) was considered as a new compound, additionally, compounds 4-O-(2-Hydroxy-1- hydroxymethylethyl)-dihydroconiferyl alcohol (2) and 5,7-dihydroxy-6-methyl-3-(2′, 4′-dihydroxybenzyl) chroman-4-one (12) were isolated from the rhizome of O. japonicas for the first time. The isolated compounds Oleic acid (3), Palmitic acid (4), desmethylisoophiopogonone B [5,7-dihydroxy-3-(4′-hydroxybenzyl)-8- methyl- chromone] (5), 5,7-dihydroxy-6-methyl-3-(4′-hydroxybenzyl) chromone (7) and 10 significantly suppressed the production of NO in LPS-induced RAW 264.7 cells. Especially compound 10 showed the strongest effect against the production of the pro-inflammatory cytokine IL-1β and IL-6 with the IC50 value of 32.5 ± 3.5 μg/mL and 13.4 ± 2.3 μg/mL, respectively. Further analysis elucidated that the anti-inflammatory activity of compound 10 might be exerted through inhibiting the phosphorylation of ERK1/2 and JNK in MAPK signaling pathways to decrease NO and pro-inflammatory cytokines production.ConclusionsOur results indicated that 4′-O-Demethylophiopogonanone E can be considered as a potential source of therapeutic medicine for inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Evaluation of anti-inflammatory activity of compounds isolated from the rhizome of Ophiopogon japonicas

Zhao

Chen

Deng³

et al. 2017

BMC Complement Altern Med

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“…In addition, MAPK signaling cascades are activated by LPS through binding of LPS to the TLR4 receptor, which is a critical factor in the signal transduction pathways involved in controlling inflammatory mediators in macrophages [42]. Several lines of evidence have shown that the activation of ERK1/2, p38, and JNK is involved in the regulation of AP-1 activity by increasing transcription [43,44]. To investigate the molecular mechanisms involved in the inhibition of inflammatory gene expression and their transcriptional activation, we examined the effects of CTB on LPS-induced MAPK phosphorylation in RAW264.7 cells using Western blot assays.…”

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory Effects of Chloranthalactone B in LPS-Stimulated RAW264.7 Cells

Shen

Jiang

Shen

et al. 2016

IJMS

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Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from the Chinese medicinal herb Sarcandra glabra, which is frequently used as a remedy for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have not been fully elucidated. In this study, we investigated the molecular mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and pro-inflammatory mediators such as prostaglandin E2, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 in RAW264.7 cells stimulated with LPS. A reverse-transcription polymerase chain reaction assay and Western blot further confirmed that CTB inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1β at the transcriptional level, and decreased the luciferase activities of activator protein (AP)-1 reporter promoters. These data suggest that inhibition occurred at the transcriptional level. In addition, CTB blocked the activation of p38 mitogen-activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our findings clearly show that CTB inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be used as an anti-inflammatory agent.

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“…Various studies have demonstrated that inhibition of NF-B activation helps to drive the tumor-promoting phenotype of TAMs to antitumor phenotype [13, 39]. Redirecting M2-like TAM toward M1-like phenotype by reactivating NF-κB induced significant antitumor immune response in mammary carcinoma [40].…”

Section: Discussionmentioning

confidence: 99%

Signal regulatory protein α associated with the progression of oral leukoplakia and oral squamous cell carcinoma regulates phenotype switch of macrophages

Zhang

et al. 2016

Oncotarget

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Signal regulatory protein a (SIRPa) is a cell-surface protein expressed on macrophages that are regarded as an important component of the tumor microenvironment. The expression of SIRPa in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and further explored the role of SIRPa on the phenotype, phagocytosis ability, migration, and invasion of macrophages in OSCC were investigated. The expression of SIRPa in OLK was higher than in OSCC, correlating with the expression of CD68 and CD163 on macrophages. After cultured with the conditioned media of oral cancer cells, the expression of SIRPa on THP-1 cells was decreased gradually. In co-culture system, macrophages were induced into M2 phenotype by oral cancer cells. Blockade of SIRPa inhibited phagocytosis ability and IL-6, TNF-a productions of macrophages. In addition, the proliferation, migration, and IL-10, TGF-β productions of macrophages were upregulated after blockade of SIRPa. Macrophages upregulated the expression of SIRPa and phagocytosis ability, and inhibited the migration and invasion when the activation of NF-kB was inhibited by pyrrolidine dithiocarbamate ammonium (PDTC). Hence, SIRPa might play an important role in the progression of OLK and oral cancer, and could be a pivotal therapeutic target in OSCC by regulating the phenotype of macrophages via targeting NF-kB.

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Antiinflammatory Activities of Crebanine by Inhibition of NF-κB and AP-1 Activation through Suppressing MAPKs and Akt Signaling in LPS-Induced RAW264.7 Macrophages

Cited by 55 publications

References 45 publications

Evaluation of anti-inflammatory activity of compounds isolated from the rhizome of Ophiopogon japonicas

Evaluation of anti-inflammatory activity of compounds isolated from the rhizome of Ophiopogon japonicas

Anti-Inflammatory Effects of Chloranthalactone B in LPS-Stimulated RAW264.7 Cells

Signal regulatory protein α associated with the progression of oral leukoplakia and oral squamous cell carcinoma regulates phenotype switch of macrophages

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