Activation of the Nrf2-antioxidant system by a novel cyclooxygenase-2 inhibitor furan-2-yl-3-pyridin-2-yl-propenone: implication in anti-inflammatory function by Nrf2 activator

Manandhar, Sarala; You, Aram; Lee, Eung-Seok; Kim, Jung-Ae; Kwak, Mi‐Kyoung

doi:10.1211/jpp.60.7.0009

Cited by 11 publications

(9 citation statements)

References 42 publications

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“…Consistent with the data published by others, we found that two cancer related genes, COX-2 and Bcl-XL, were upregulated in UVA irradiated HaCaT cells 44, 50, 51 ; 49, 52 . Notably, expression of both genes is dependent upon activation of p38, since inhibition of p38 with SB202190 abolishes their induction in UVA irradiated HaCaT cells 44, 49 .…”

Section: Signaling Pathways Activated By Uva In Human Kertinocytessupporting

confidence: 93%

Activation of p38 MAP kinase and JNK pathways by UVA irradiation

Zhang

Bowden

2012

Photochem Photobiol Sci

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There are more than two million new cases of non-melanoma skin cancers (NMSCs) diagnosed each year in the United States. The clear etiological factor is chronic exposure to solar radiation from the sun. The wavelengths of solar light that reach the earth’s surface include UVB (280-320nm) which accounts for 1-10% and UVA (320-400nm) which accounts for 90-99% of the radiation. While most of the published research has focused on the effects of UVB, little is known concerning UVA-mediated signal transduction pathways and their role in skin tumor promotion and progression giving rise to squamous cell carcinomas (SCCs). Here we have focused on UVA-mediated activation of p38 MAP kinase and c-Jun N-terminal kinase (JNK) and their roles in activator protein-1 (AP-1) mediated transcription, cyclooxygenase-2 (COX-2) and Bcl-XL expression. Since p38 MAP kinase and JNK play major roles in the expression of UVA-induced AP-1, COX-2 and Bcl-XL, pharmacological inhibitors of these kinases may be useful in the chemoprevention of SCC skin cancer.

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Section: Signaling Pathways Activated By Uva In Human Kertinocytessupporting

confidence: 93%

Activation of p38 MAP kinase and JNK pathways by UVA irradiation

Zhang

Bowden

2012

Photochem Photobiol Sci

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“…Moreover, FPP‐3 was shown to inhibit NF‐κβ activation in vitro leading to the decrease of iNOS expression and TNF‐α biosynthesis . Finally, a variety of other beneficial actions of FPP‐3 have been reported, such as chemopreventive effects, antioxidant properties, and anti‐angiogenic actions, broadening the spectrum of potential application for this drug …”

Section: Identification Of Novel Targets In the Arachidonic Acid Cascadementioning

confidence: 99%

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

Pereira-Leite

Nunes

Jamal

et al. 2016

Medicinal Research Reviews

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The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) against inflammation, pain, and fever has been supporting their worldwide use in the treatment of painful conditions and chronic inflammatory diseases until today. However, the long-term therapy with NSAIDs was soon associated with high incidences of adverse events in the gastrointestinal tract. Therefore, the search for novel drugs with improved safety has begun with COX-2 selective inhibitors (coxibs) being straightaway developed and commercialized. Nevertheless, the excitement has fast turned to disappointment when diverse coxibs were withdrawn from the market due to cardiovascular toxicity. Such events have once again triggered the emergence of different strategies to overcome NSAIDs toxicity. Here, an integrative review is provided to address the breakthroughs of two main approaches: (i) the association of NSAIDs with protective mediators and (ii) the design of novel compounds to target downstream and/or multiple enzymes of the arachidonic acid cascade. To date, just one phosphatidylcholine-associated NSAID has already been approved for commercialization. Nevertheless, the preclinical and clinical data obtained so far indicate that both strategies may improve the safety of nonsteroidal anti-inflammatory therapy.

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“…Flavonoids, including flavones, flavanols and condensed tannins, are plant secondary metabolites and these phenolic compounds have redox properties, which allow them to act as antioxidants [23]. Furthermore, flavonoids activate Antioxidant Responsive Element (ARE) through Nrf2 pathway to counteract proinflammatory mediator such as TNF α and COX induced inflammation [24][25][26].…”

Section: Total Flavonoid and Phenolic Contentsmentioning

confidence: 99%

“…Thanks to activation of aredox-sensitive gene regulatory network mediated by the NF-E2-related factor-2 (Nrf2) which is involved in response tooxidativestress and xenobiotics, mediatedthrough Antioxidant Responsive Element (ARE). Phenolic compounds such as flavonoids activates Antioxidant Responsive Element (ARE) through Nrf2 pathway to counteract proinflammatory induced inflammation [24][25][26]. Similarly, phenolics countering oxidative stress invarious pathological condition, few to be mentioned as in cancer cell lines and hypoxia for this reason increasingly being used as therapeutic agent.…”

Section: Antioxidant Activitymentioning

confidence: 99%

In-vitro antioxidant, Xanthine oxidase-inhibitory and in-vivo Anti-inflammatory, analgesic, antipyretic activity of Onopordum acanthium

Habibatni¹,

Zohra²,

Khalida³

et al. 2017

ijpm

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Onopordum acanthium (Scotch thistle) belong to Asteraceae (Compositae). O. acanthium is a flowering biennial plant native to Europe and Western Asia with coarse spiny leaves 20-50 cm in width with conspicuous and spiny-winged stems. We have previously reported pro-apoptotic and cytotoxic effect of Onopordum acanthium crude extract against glioblastoma U-373 cells. The present study was designed to evaluate the cytotoxicity, antioxidant, xanthine oxidase inhibition, anti-inflammatory, analgesic, antipyretic activity of butanolic extract of Onopordum acanthium. Cytotoxicity of different solvent (methanolic, butanol, chloroform and petroleum ether) extract studied by brine shrimp lethality bioassay, total flavonoid and phenolic, antioxidant, xanthine oxidase inhibition activity was studied by in-vitro whereas anti- inflammation studied by carrageenan-induced paw edema model, antipyretic with 20 % brew yeast injection induced pyretic model, analgesic with 1 % acetic acid induced analgesic model investigated in in-vivo in wistar rats. Good antioxidant activity was found with IC50 = 134.4 µg/ml with considerable amount of total phenolic and flavonoid content. Xanthine oxidase inhibition effect was weak with IC50 = 572.9 µg/ml. Oral administration of O. Acanthium butanolic extract (OA) showed minimum lethality of brine shrimp nauplii henceforth OA butanolic phases was selected for further in-vivo studies. OA 200 and 400 mg/kg body weight decreased the oedema by 37.78 % and 40.52 %, respectively; standard aspirin 100 mg/kg decreased 42.62 % at 5th hour of Carrageenan injection. OA 200 and 400 mg/kg significantly decreased acetic acid-induced abdominal writhes when compared to standard aspirin. OA have shown dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, aspirin. The present results demonstrate that OA has notable anti-inflammatory, antipyretic, analgesic activity related to presence of phenolic compounds as from literature it has been demonstrated that isolated compounds from aerial parts of Onopordum acanthium had strong activity in in-vitro assay.

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Activation of the Nrf2-antioxidant system by a novel cyclooxygenase-2 inhibitor furan-2-yl-3-pyridin-2-yl-propenone: implication in anti-inflammatory function by Nrf2 activator

Cited by 11 publications

References 42 publications

Activation of p38 MAP kinase and JNK pathways by UVA irradiation

Activation of p38 MAP kinase and JNK pathways by UVA irradiation

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

In-vitro antioxidant, Xanthine oxidase-inhibitory and in-vivo Anti-inflammatory, analgesic, antipyretic activity of <em>Onopordum acanthium</em>

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