Open Access

ARTICLE

Isorhynchophylline Suppresses Eicosanoid Production via miR-200a-Mediated Inhibition of the FOXC1/NF-κB Axis in Inflammatory Macrophages

Lu Yang^1,#, Man Tian^2,#, Jinyue Zhu^1,*

1 Department of Respiratory Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
2 Department of Endocrinology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China

* Corresponding Author: Jinyue Zhu. Email:
# These authors contributed equally to this work

BIOCELL 2026, 50(10), 11 https://doi.org/10.32604/biocell.2026.082951

Received 26 March 2026; Accepted 04 June 2026; Issue published 22 September 2026

Abstract

Background: Macrophage-derived eicosanoids are involved in airway inflammation associated with asthma, but the mechanisms regulating their production remain incompletely understood. The study aimed to evaluate the effects of isorhynchophylline (IRN) on eicosanoid production and inflammatory activation in LPS/IFN-γ-stimulated THP-1-derived macrophages and to further investigate whether these effects are mediated through the miR-200a/FOXC1/NF-κB axis. Methods: THP-1 cells were differentiated into M0 (PMA) and polarized into M1 (LPS+IFN-γ) phenotypes. IRN (5–20 μM) was applied. Eicosanoids (PGE₂, LTB₄) were measured via ELISA; COX-2, 5-LOX, mPGES-1, FOXC1, p-IκBα/IκBα, and p-p65/p65 were measured via Western blotting; and miR-200a and target genes were measured via RT-qPCR. Polarization markers (CD86/CD206, TNF-α/IL-10, and iNOS/Arg1) were assessed. Results: IRN dose-dependently reduced PGE₂ and LTB₄ release and downregulated COX-2, 5-LOX, and mPGES-1 expression in LPS/IFN-γ-stimulated macrophages (p < 0.05). IRN increased miR-200a expression, suppressed FOXC1 expression, and attenuated NF-κB activation, as indicated by reduced p-IκBα/IκBα and p-p65/p65 levels and decreased nuclear p65 accumulation (p < 0.01). IRN also reduced M1-associated markers, including CD86, iNOS, and TNF-α, while increasing M2-associated markers, including CD206, Arg1, and IL-10 (p < 0.01). miR-200a knockdown weakened the inhibitory effects of IRN on FOXC1/NF-κB signaling and eicosanoid-producing enzymes, whereas miR-200a overexpression reproduced these effects (p < 0.001). Dual-luciferase assays confirmed that miR-200a directly bound to the FOXC1 3′UTR. FOXC1 overexpression or NF-κB activation partially reversed the suppressive effects of IRN, whereas NF-κB inhibition mimicked the IRN-induced phenotype (p < 0.01). Conclusions: IRN suppresses eicosanoid production and inflammatory activation in LPS/IFN-γ-stimulated THP-1-derived macrophages, partly through the miR-200a/FOXC1/NF-κB axis. These findings provide cell-based mechanistic evidence that requires validation in primary airway macrophages and disease-specific models.

---

Keywords

---