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Objective <p>Activated macrophages play important roles during immune responses by polarizing into M1 and M2 subsets and overproducing several mediators such as nitric oxide (NO), pro- and anti-inflammatory cytokines, and indoleamine 2,3-dioxygenase (IDO). This study aims to investigate the possible effects of piperine, a major component of the pepper plant, on the expression of M1 and M2 macrophage markers.</p> Results <p>Piperine dose-dependently decreased <i>iNOS</i> gene expression and NO level in LPS-stimulated macrophages. Additionally, at concentrations of 1–20&#xa0;µg/ml, it significantly suppressed the production and/or gene expression levels of proinflammatory M1-related cytokines. Its effects on cytokine genes were dose-dependent, and reduced <i>IL-1β</i>,<i> TNF-α</i>, and <i>IFN-γ</i> expression (17 ± 11.8, 1.33 ± 0.76, and 25.4 ± 5.2 fold, respectively, compared with LPS-stimulated cells). Piperine at 1&#xa0;µg/ml didn’t affect the <i>IL-10</i> gene but significantly increased <i>IDO1</i> (from 8.4 ± 0.24-fold in LPS-treated cells to 28.3 ± 5.3-fold in piperine-treated cells), and decreased <i>IL-4</i> gene expressions at the higher concentrations. Dexamethasone (a glucocorticoid anti-inflammatory drug) reduced most mediators but did not affect the <i>IDO</i> gene. Our data demonstrate that piperine dose-dependently inhibits M1-macrophages and upregulates <i>IDO1</i> at low concentration, a unique mechanism of action, positioning it as a multifaceted therapeutic candidate for inflammatory conditions.</p>

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Piperine suppresses M1 phenotype and induces indoleamine 2,3-dioxygenase gene in LPS-stimulated murine macrophage cell line

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月12日

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  • Nasser Gholijani,
  • Zeinab Dehghan,
  • Samira Sadat Abolmaali,
  • Atefe Ghamar Talepoor,
  • Kurosh Kalantar,
  • Gholamreza Daryabor

摘要

Objective

Activated macrophages play important roles during immune responses by polarizing into M1 and M2 subsets and overproducing several mediators such as nitric oxide (NO), pro- and anti-inflammatory cytokines, and indoleamine 2,3-dioxygenase (IDO). This study aims to investigate the possible effects of piperine, a major component of the pepper plant, on the expression of M1 and M2 macrophage markers.

Results

Piperine dose-dependently decreased iNOS gene expression and NO level in LPS-stimulated macrophages. Additionally, at concentrations of 1–20 µg/ml, it significantly suppressed the production and/or gene expression levels of proinflammatory M1-related cytokines. Its effects on cytokine genes were dose-dependent, and reduced IL-1β, TNF-α, and IFN-γ expression (17 ± 11.8, 1.33 ± 0.76, and 25.4 ± 5.2 fold, respectively, compared with LPS-stimulated cells). Piperine at 1 µg/ml didn’t affect the IL-10 gene but significantly increased IDO1 (from 8.4 ± 0.24-fold in LPS-treated cells to 28.3 ± 5.3-fold in piperine-treated cells), and decreased IL-4 gene expressions at the higher concentrations. Dexamethasone (a glucocorticoid anti-inflammatory drug) reduced most mediators but did not affect the IDO gene. Our data demonstrate that piperine dose-dependently inhibits M1-macrophages and upregulates IDO1 at low concentration, a unique mechanism of action, positioning it as a multifaceted therapeutic candidate for inflammatory conditions.