Eupafolin ameliorates COX-2 expression and PGE 2 production in particulate pollutants-exposed human keratinocytes through ROS/MAPKs pathways

Chiang Wen Lee, Zih Chan Lin, Lee Fen Hsu, Jia You Fang, Yao Chang Chiang, Ming Horng Tsai, Ming Hsueh Lee, Shu Yu Li, Stephen Chu Sung Hu, I-Ta Lee, Feng Lin Yen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Ethnopharmacological relevance Eupafolin is a major bioactive compound derived from the methanolic extract of the medicinal herb Phyla nodiflora, which has been used in traditional Chinese medicine to treat various inflammatory diseases. Recently, particulate air pollutants have been shown to induce inflammation of the skin. In this study, we seek to determine whether eupafolin can inhibit the production of inflammatory mediators in a human skin keratinocyte cell line exposed to particulate air pollutants (particulate matter, PM), and determine the molecular mechanisms involved. Materials and methods Human keratinocyte HaCaT cells were treated with PM in the presence or absence of eupafolin. Cyclooxygenase-2 (COX-2) protein and gene expression levels were determined by Western blotting, RT-PCR and luciferase activity assay. Prostaglandin E 2 (PGE 2 ) production was evaluated by the enzyme immunoassay method. Generation of intracellular reactive oxygen species (ROS) was measured by the dichlorofluorescin (DCFH) oxidation assay, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was determined by a chemiluminescence assay. For in vivo studies, COX-2 expression in the skin of BALB/c nude mice was analyzed by immunohistochemistry. Results Eupafolin inhibited PM-induced COX-2 protein and gene expression and PGE 2 production in HaCaT cells. In addition, eupafolin suppressed PM-induced intracellular ROS generation, NADPH oxidase activity, MAPK (ERK, JNK and p38) activation and NK-κB activation. In vivo studies showed that topical treatment with eupafolin inhibited COX-2 expression in the epidermal keratinocytes of PM-treated mice. Conclusions Eupafolin exerts anti-inflammatory and antioxidant effects on skin keratinocytes exposed to particulate air pollutants, and may have potential use in the treatment or prevention of air pollutant-induced inflammatory skin diseases in the future.

Original languageEnglish
Pages (from-to)300-309
Number of pages10
JournalJournal of Ethnopharmacology
Volume189
DOIs
Publication statusPublished - Aug 2 2016
Externally publishedYes

Fingerprint

Particulate Matter
Cyclooxygenase 2
Prostaglandins E
Keratinocytes
Reactive Oxygen Species
Skin
NADP
Oxidoreductases
Gene Expression
Air Pollutants
eupafolin
Chinese Traditional Medicine
Medicinal Plants
Luminescence
Luciferases
Immunoenzyme Techniques
Skin Diseases
Nude Mice
Proteins
Anti-Inflammatory Agents

Keywords

  • cyclooxygenase-2
  • Eupafolin
  • keratinocytes
  • particulate matter
  • Phyla nodiflora
  • prostaglandin E

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Eupafolin ameliorates COX-2 expression and PGE 2 production in particulate pollutants-exposed human keratinocytes through ROS/MAPKs pathways. / Lee, Chiang Wen; Lin, Zih Chan; Hsu, Lee Fen; Fang, Jia You; Chiang, Yao Chang; Tsai, Ming Horng; Lee, Ming Hsueh; Li, Shu Yu; Hu, Stephen Chu Sung; Lee, I-Ta; Yen, Feng Lin.

In: Journal of Ethnopharmacology, Vol. 189, 02.08.2016, p. 300-309.

Research output: Contribution to journalArticle

Lee, Chiang Wen ; Lin, Zih Chan ; Hsu, Lee Fen ; Fang, Jia You ; Chiang, Yao Chang ; Tsai, Ming Horng ; Lee, Ming Hsueh ; Li, Shu Yu ; Hu, Stephen Chu Sung ; Lee, I-Ta ; Yen, Feng Lin. / Eupafolin ameliorates COX-2 expression and PGE 2 production in particulate pollutants-exposed human keratinocytes through ROS/MAPKs pathways. In: Journal of Ethnopharmacology. 2016 ; Vol. 189. pp. 300-309.
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abstract = "Ethnopharmacological relevance Eupafolin is a major bioactive compound derived from the methanolic extract of the medicinal herb Phyla nodiflora, which has been used in traditional Chinese medicine to treat various inflammatory diseases. Recently, particulate air pollutants have been shown to induce inflammation of the skin. In this study, we seek to determine whether eupafolin can inhibit the production of inflammatory mediators in a human skin keratinocyte cell line exposed to particulate air pollutants (particulate matter, PM), and determine the molecular mechanisms involved. Materials and methods Human keratinocyte HaCaT cells were treated with PM in the presence or absence of eupafolin. Cyclooxygenase-2 (COX-2) protein and gene expression levels were determined by Western blotting, RT-PCR and luciferase activity assay. Prostaglandin E 2 (PGE 2 ) production was evaluated by the enzyme immunoassay method. Generation of intracellular reactive oxygen species (ROS) was measured by the dichlorofluorescin (DCFH) oxidation assay, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was determined by a chemiluminescence assay. For in vivo studies, COX-2 expression in the skin of BALB/c nude mice was analyzed by immunohistochemistry. Results Eupafolin inhibited PM-induced COX-2 protein and gene expression and PGE 2 production in HaCaT cells. In addition, eupafolin suppressed PM-induced intracellular ROS generation, NADPH oxidase activity, MAPK (ERK, JNK and p38) activation and NK-κB activation. In vivo studies showed that topical treatment with eupafolin inhibited COX-2 expression in the epidermal keratinocytes of PM-treated mice. Conclusions Eupafolin exerts anti-inflammatory and antioxidant effects on skin keratinocytes exposed to particulate air pollutants, and may have potential use in the treatment or prevention of air pollutant-induced inflammatory skin diseases in the future.",
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author = "Lee, {Chiang Wen} and Lin, {Zih Chan} and Hsu, {Lee Fen} and Fang, {Jia You} and Chiang, {Yao Chang} and Tsai, {Ming Horng} and Lee, {Ming Hsueh} and Li, {Shu Yu} and Hu, {Stephen Chu Sung} and I-Ta Lee and Yen, {Feng Lin}",
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T1 - Eupafolin ameliorates COX-2 expression and PGE 2 production in particulate pollutants-exposed human keratinocytes through ROS/MAPKs pathways

AU - Lee, Chiang Wen

AU - Lin, Zih Chan

AU - Hsu, Lee Fen

AU - Fang, Jia You

AU - Chiang, Yao Chang

AU - Tsai, Ming Horng

AU - Lee, Ming Hsueh

AU - Li, Shu Yu

AU - Hu, Stephen Chu Sung

AU - Lee, I-Ta

AU - Yen, Feng Lin

PY - 2016/8/2

Y1 - 2016/8/2

N2 - Ethnopharmacological relevance Eupafolin is a major bioactive compound derived from the methanolic extract of the medicinal herb Phyla nodiflora, which has been used in traditional Chinese medicine to treat various inflammatory diseases. Recently, particulate air pollutants have been shown to induce inflammation of the skin. In this study, we seek to determine whether eupafolin can inhibit the production of inflammatory mediators in a human skin keratinocyte cell line exposed to particulate air pollutants (particulate matter, PM), and determine the molecular mechanisms involved. Materials and methods Human keratinocyte HaCaT cells were treated with PM in the presence or absence of eupafolin. Cyclooxygenase-2 (COX-2) protein and gene expression levels were determined by Western blotting, RT-PCR and luciferase activity assay. Prostaglandin E 2 (PGE 2 ) production was evaluated by the enzyme immunoassay method. Generation of intracellular reactive oxygen species (ROS) was measured by the dichlorofluorescin (DCFH) oxidation assay, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was determined by a chemiluminescence assay. For in vivo studies, COX-2 expression in the skin of BALB/c nude mice was analyzed by immunohistochemistry. Results Eupafolin inhibited PM-induced COX-2 protein and gene expression and PGE 2 production in HaCaT cells. In addition, eupafolin suppressed PM-induced intracellular ROS generation, NADPH oxidase activity, MAPK (ERK, JNK and p38) activation and NK-κB activation. In vivo studies showed that topical treatment with eupafolin inhibited COX-2 expression in the epidermal keratinocytes of PM-treated mice. Conclusions Eupafolin exerts anti-inflammatory and antioxidant effects on skin keratinocytes exposed to particulate air pollutants, and may have potential use in the treatment or prevention of air pollutant-induced inflammatory skin diseases in the future.

AB - Ethnopharmacological relevance Eupafolin is a major bioactive compound derived from the methanolic extract of the medicinal herb Phyla nodiflora, which has been used in traditional Chinese medicine to treat various inflammatory diseases. Recently, particulate air pollutants have been shown to induce inflammation of the skin. In this study, we seek to determine whether eupafolin can inhibit the production of inflammatory mediators in a human skin keratinocyte cell line exposed to particulate air pollutants (particulate matter, PM), and determine the molecular mechanisms involved. Materials and methods Human keratinocyte HaCaT cells were treated with PM in the presence or absence of eupafolin. Cyclooxygenase-2 (COX-2) protein and gene expression levels were determined by Western blotting, RT-PCR and luciferase activity assay. Prostaglandin E 2 (PGE 2 ) production was evaluated by the enzyme immunoassay method. Generation of intracellular reactive oxygen species (ROS) was measured by the dichlorofluorescin (DCFH) oxidation assay, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was determined by a chemiluminescence assay. For in vivo studies, COX-2 expression in the skin of BALB/c nude mice was analyzed by immunohistochemistry. Results Eupafolin inhibited PM-induced COX-2 protein and gene expression and PGE 2 production in HaCaT cells. In addition, eupafolin suppressed PM-induced intracellular ROS generation, NADPH oxidase activity, MAPK (ERK, JNK and p38) activation and NK-κB activation. In vivo studies showed that topical treatment with eupafolin inhibited COX-2 expression in the epidermal keratinocytes of PM-treated mice. Conclusions Eupafolin exerts anti-inflammatory and antioxidant effects on skin keratinocytes exposed to particulate air pollutants, and may have potential use in the treatment or prevention of air pollutant-induced inflammatory skin diseases in the future.

KW - cyclooxygenase-2

KW - Eupafolin

KW - keratinocytes

KW - particulate matter

KW - Phyla nodiflora

KW - prostaglandin E

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