Anti-Inflammatory Effect of Pestalotic Acid A Derived from <i>Pestalotiopsis vismiae,</i> an Endophytic Fungus of <i>Ilex prenatal</i>, in Lipopolysaccharide-Stimulated RAW264.7 Cells

<b>Background/Objectives:</b> Pestalotic acid A (PAA), a polyketide derived from <i>Pestalotiopsis vismiae</i>, an endophyte of the Japanese holly (<i>Ilex crenata</i>), is known to exhibit known antimicrobial activity, but its anti-inflammatory properties remain...

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Main Authors: Da Young Hwang, Dae-Won Ki, Dae-Cheol Choi, Bong-Sik Yun, Yoon Hee Kim
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/6/1445
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author Da Young Hwang
Dae-Won Ki
Dae-Cheol Choi
Bong-Sik Yun
Yoon Hee Kim
author_facet Da Young Hwang
Dae-Won Ki
Dae-Cheol Choi
Bong-Sik Yun
Yoon Hee Kim
author_sort Da Young Hwang
collection DOAJ
description <b>Background/Objectives:</b> Pestalotic acid A (PAA), a polyketide derived from <i>Pestalotiopsis vismiae</i>, an endophyte of the Japanese holly (<i>Ilex crenata</i>), is known to exhibit known antimicrobial activity, but its anti-inflammatory properties remain uncharacterized. This study aimed to investigate the anti-inflammatory effects of PAA in lipopolysaccharide (LPS)-stimulated murine macrophages, RAW264.7 cells. <b>Methods:</b> PAA was isolated from <i>P. vismiae</i> endophytes of <i>Ilex crenata,</i> and its structure was confirmed. RAW264.7 macrophages were treated with 0–50 μM of PAA in the presence of 100 ng/mL LPS. Cell viability was assessed by MTS assay; nitric oxide (NO) production was measured via Griess reagent; interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF) were quantified by enzyme-linked immunosorbent assay. Protein expression of inducible NO synthase (iNOS), nuclear factor (NF)-κB p65 phosphorylation, and related signaling proteins was evaluated by Western blot analysis and immunofluorescence staining. <b>Results:</b> PAA significantly increased macrophage viability and dose-dependently inhibited the release of NO by alleviating the protein expression of iNOS in LPS-treated RAW264.7 cells. Furthermore, PAA suppressed the release of IL-6, IL-1β, and TNF induced by LPS. Western blot and immunofluorescence results also indicated that PAA blocked the p65 subunit phosphorylation of NF-κB, which is one of the underlying mechanisms of the anti-inflammatory action of pestalotic acid A. <b>Conclusions:</b> PAA exerts potent anti-inflammatory effects in LPS-stimulated macrophages via inhibition of the NF-κB pathway, highlighting its potential as a natural therapeutic agent for inflammatory diseases.
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spelling doaj-art-dbb9bcd91cce496c80d7904599d28f482025-06-25T13:32:02ZengMDPI AGBiomedicines2227-90592025-06-01136144510.3390/biomedicines13061445Anti-Inflammatory Effect of Pestalotic Acid A Derived from <i>Pestalotiopsis vismiae,</i> an Endophytic Fungus of <i>Ilex prenatal</i>, in Lipopolysaccharide-Stimulated RAW264.7 CellsDa Young Hwang0Dae-Won Ki1Dae-Cheol Choi2Bong-Sik Yun3Yoon Hee Kim4Department of Food and Nutrition, College of Engineering, Daegu University, Gyeongsan-si 38453, Republic of KoreaDivision of Biotechnology, Jeonbuk National University, Iksan-si 54596, Republic of KoreaDivision of Biotechnology, Jeonbuk National University, Iksan-si 54596, Republic of KoreaDivision of Biotechnology, Jeonbuk National University, Iksan-si 54596, Republic of KoreaDepartment of Food and Nutrition, College of Engineering, Daegu University, Gyeongsan-si 38453, Republic of Korea<b>Background/Objectives:</b> Pestalotic acid A (PAA), a polyketide derived from <i>Pestalotiopsis vismiae</i>, an endophyte of the Japanese holly (<i>Ilex crenata</i>), is known to exhibit known antimicrobial activity, but its anti-inflammatory properties remain uncharacterized. This study aimed to investigate the anti-inflammatory effects of PAA in lipopolysaccharide (LPS)-stimulated murine macrophages, RAW264.7 cells. <b>Methods:</b> PAA was isolated from <i>P. vismiae</i> endophytes of <i>Ilex crenata,</i> and its structure was confirmed. RAW264.7 macrophages were treated with 0–50 μM of PAA in the presence of 100 ng/mL LPS. Cell viability was assessed by MTS assay; nitric oxide (NO) production was measured via Griess reagent; interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF) were quantified by enzyme-linked immunosorbent assay. Protein expression of inducible NO synthase (iNOS), nuclear factor (NF)-κB p65 phosphorylation, and related signaling proteins was evaluated by Western blot analysis and immunofluorescence staining. <b>Results:</b> PAA significantly increased macrophage viability and dose-dependently inhibited the release of NO by alleviating the protein expression of iNOS in LPS-treated RAW264.7 cells. Furthermore, PAA suppressed the release of IL-6, IL-1β, and TNF induced by LPS. Western blot and immunofluorescence results also indicated that PAA blocked the p65 subunit phosphorylation of NF-κB, which is one of the underlying mechanisms of the anti-inflammatory action of pestalotic acid A. <b>Conclusions:</b> PAA exerts potent anti-inflammatory effects in LPS-stimulated macrophages via inhibition of the NF-κB pathway, highlighting its potential as a natural therapeutic agent for inflammatory diseases.https://www.mdpi.com/2227-9059/13/6/1445endophytic fungiinflammationmacrophagepestalotic acid AJapanese holly
spellingShingle Da Young Hwang
Dae-Won Ki
Dae-Cheol Choi
Bong-Sik Yun
Yoon Hee Kim
Anti-Inflammatory Effect of Pestalotic Acid A Derived from <i>Pestalotiopsis vismiae,</i> an Endophytic Fungus of <i>Ilex prenatal</i>, in Lipopolysaccharide-Stimulated RAW264.7 Cells
Biomedicines
endophytic fungi
inflammation
macrophage
pestalotic acid A
Japanese holly
title Anti-Inflammatory Effect of Pestalotic Acid A Derived from <i>Pestalotiopsis vismiae,</i> an Endophytic Fungus of <i>Ilex prenatal</i>, in Lipopolysaccharide-Stimulated RAW264.7 Cells
title_full Anti-Inflammatory Effect of Pestalotic Acid A Derived from <i>Pestalotiopsis vismiae,</i> an Endophytic Fungus of <i>Ilex prenatal</i>, in Lipopolysaccharide-Stimulated RAW264.7 Cells
title_fullStr Anti-Inflammatory Effect of Pestalotic Acid A Derived from <i>Pestalotiopsis vismiae,</i> an Endophytic Fungus of <i>Ilex prenatal</i>, in Lipopolysaccharide-Stimulated RAW264.7 Cells
title_full_unstemmed Anti-Inflammatory Effect of Pestalotic Acid A Derived from <i>Pestalotiopsis vismiae,</i> an Endophytic Fungus of <i>Ilex prenatal</i>, in Lipopolysaccharide-Stimulated RAW264.7 Cells
title_short Anti-Inflammatory Effect of Pestalotic Acid A Derived from <i>Pestalotiopsis vismiae,</i> an Endophytic Fungus of <i>Ilex prenatal</i>, in Lipopolysaccharide-Stimulated RAW264.7 Cells
title_sort anti inflammatory effect of pestalotic acid a derived from i pestalotiopsis vismiae i an endophytic fungus of i ilex prenatal i in lipopolysaccharide stimulated raw264 7 cells
topic endophytic fungi
inflammation
macrophage
pestalotic acid A
Japanese holly
url https://www.mdpi.com/2227-9059/13/6/1445
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