ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1646545
This article is part of the Research TopicInnovations in targeting intestinal immunity for chronic inflammatory disordersView all articles
Zuoqing Granules Attenuate Ulcerative Colitis via Macrophage Polarization Modulation: Involvement of PPAR-γ/NF-κB/STAT1 Signaling axis
Provisionally accepted
- 1Department of Anorectal surgery,Second affiliciated hospital, Anhui university of chinese medicine, Hefei, China., Hefei, China
- 2Department of Anorectal Medicine,, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
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Background: Although our prior clinical study demonstrated the efficacy of Zuoqing Granules (ZQG) in treating ulcerative colitis (UC), the underlying immunomodulatory mechanisms remained unclear. This study systematically investigated ZQG's therapeutic effects through macrophage polarization modulation and related signaling pathways using both in vivo and in vitro models. Methods: In vivo, DSS-induced UC rats were divided into normal control, dextran sulfate sodium (DSS) model, and ZQG treatment groups (high/medium/low doses). Colon tissues were analyzed using: histopathology (HE staining), macrophage phenotyping (CD86+/CD206+ immunofluorescence and flow cytometry), signaling pathway assessment (PPAR-γ, NF-κBp65, p-NF-κBp65, STAT1 by Western blot/qPCR), cytokine profiling (TNF-α, IL-6, IL-10, IL-1β, IL-4 by ELISA). In vitro, LPSstimulated RAW264.7 macrophages were treated with ZQG-conditioned medium ± PPAR-γ antagonist (GW9662) to validate direct effects. Results: ZQG treatment dose-dependently: (1) ameliorated colonic mucosal damage, reducing histological scores by 52% compared to model group; (2) modulated macrophage polarization by increasing M2 phenotype (CD206+ cells, 3.25-fold increase) while decreasing M1 macrophages (CD86+ cells, 70% reduction); (3) upregulated PPAR-γ expression (2.0-fold increase) while suppressing NF-κB activation (43% decrease in p-NF-κB) and STAT1 signaling (48% and 40% reductions in protein and mRNA levels, respectively); and (4) rebalanced inflammatory cytokines, with 55-62% reductions in TNF-α, IL-6 and IL-1β, and 185-210% elevation in IL-10, IL-4. In vitro studies further confirmed that ZQG directly shifted macrophage polarization via PPAR-γ, inhibiting M1 polarization (an effect abolished by GW9662). Conclusion: ZQG ameliorates UC by modulating macrophage plasticity through the PPAR-γ/NF-κB/STAT1 axis, a mechanism validated in vitro as PPAR-γ-dependent. These findings elucidate its clinical efficacy and support its use as a multi-target UC therapy.
Keywords: Zuoqing Granules, ulcerative colitis, Macrophage polarization, PPARγ/NF-κB/STAT1 signaling, Traditional Chinese Medicine
Received: 16 Jun 2025; Accepted: 23 Jul 2025.
Copyright: © 2025 Deng, Li, Fang, Tang and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ming Li, Department of Anorectal Medicine,, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
Kun Tang, Department of Anorectal Medicine,, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
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