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: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/6/1445 |
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| Summary: | <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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| ISSN: | 2227-9059 |