Immunomodulatory Effects of Ferula assa-foetida Extract on NF-κB and STAT1 Signaling Pathways in GM-CSF-Differentiated Human Macrophages

Document Type : Original Article

Authors

1 Dept. of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran

2 دانشکده علوم، گروه زیست شناسی، دانشگاه سیستان و بلوچستان

Abstract

The immunomodulatory properties of Ferula assa-foetida, a perennial herb traditionally used for its anti-inflammatory effects, were investigated in this study, focusing on its influence on NF-κB and STAT1 signaling pathways in GM-CSF-differentiated human macrophages. The extract was prepared using 80% ethanol, and its cytotoxicity was evaluated using the MTT assay, revealing no significant cytotoxic effects at concentrations ranging from 10 to 200 µg/mL. Differentiated macrophages were treated with the extract, and quantitative real-time PCR (qRT-PCR) was employed to assess the expression levels of NF-κB and STAT1 genes. The results demonstrated a dose-dependent downregulation of NF-κB expression by the extract, with significant reductions observed at concentrations of 50 µg/mL and higher. Specifically, NF-κB expression decreased to 0.6719 ± 0.0691-fold at 50 µg/mL (p = 0.0044), 0.3959 ± 0.1170-fold at 100 µg/mL (p = 0.0009), and 0.1650 ± 0.0509-fold at 200 µg/mL (p < 0.0001). In contrast, STAT1 expression remained unaffected across all tested concentrations of the extract, with no statistically significant changes compared to the untreated control group. Lipopolysaccharide (LPS), used as a positive control, significantly upregulated both NF-κB and STAT1 expression, confirming the responsiveness of the macrophages to inflammatory stimuli. These findings suggest that the extract selectively modulates NF-κB-dependent inflammatory pathways without broadly affecting STAT1 signaling. The study highlights the potential of F. assa-foetida as a source of bioactive compounds with anti-inflammatory properties. However, further research is needed to elucidate the underlying molecular mechanisms, identify the active compounds, and validate these effects in vivo.

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