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Purpose <p>Atractylenolide III (AT-III) exhibits notable anti-inflammatory, neuroprotective, and gastroprotective properties; however, its protective mechanisms in the gastric mucosa remain unclear. This study aimed to investigate the protective effects and mechanism of action of AT-III against indomethacin (IND)-induced gastric mucosal injury in rats.</p> Methods <p>Network pharmacological approaches were used to predict the therapeutic potential and underlying mechanisms of AT-III in gastric ulcers (GU). Gastric mucosal morphology and ultrastructure were assessed using hematoxylin and eosin (HE) staining, periodic acid-Schiff (PAS) staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Molecular docking was used to predict the binding affinity of AT-III with key molecular targets in the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathway. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence assays were employed to detect the expression levels of Raf, MEK1/2, ERK1, IκBβ, IKKβ, and NF-κB in rat gastric tissues to verify the effects of AT-III on IND-induced GU and MAPK/NF-κB-mediated inflammatory responses.</p> Results <p>Histological and ultrastructural analyses revealed significant improvements in rat gastric mucosa following AT-III treatment. Molecular docking indicated strong binding affinity of AT-III to MAPK/NF-κB pathway targets. Subsequent qRT-PCR and immunofluorescence experiments confirmed these findings, demonstrating that AT-III downregulated mRNA and protein expressions of Raf, MEK1/2, ERK1, IκBβ, IKKβ, and NF-κB in rats.</p> Conclusion <p>By inhibiting pivotal regulators within the MAPK/NF-κB signaling cascade, AT-III effectively reduced local inflammation, ameliorated the pathological morphology of IND-induced GU in rats, and enhanced therapeutic outcomes, indicating its potential as a therapeutic agent for GU.</p>

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Atractylenolide III as a novel therapeutic strategy for gastric ulcer: mechanistic insights and investigation of molecular targets

  • 期刊论文

  • 发表日期：

    2025年7月29日

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  • Shunhua Zhou,
  • Jun Peng,
  • Qing Gao,
  • Meng Xiong,
  • Baoping Ren,
  • Xiaojuan Wang,
  • Beibei Wang,
  • Zeru Liu,
  • Meiyan Zeng,
  • Houpan Song

摘要

Purpose

Atractylenolide III (AT-III) exhibits notable anti-inflammatory, neuroprotective, and gastroprotective properties; however, its protective mechanisms in the gastric mucosa remain unclear. This study aimed to investigate the protective effects and mechanism of action of AT-III against indomethacin (IND)-induced gastric mucosal injury in rats.

Methods

Network pharmacological approaches were used to predict the therapeutic potential and underlying mechanisms of AT-III in gastric ulcers (GU). Gastric mucosal morphology and ultrastructure were assessed using hematoxylin and eosin (HE) staining, periodic acid-Schiff (PAS) staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Molecular docking was used to predict the binding affinity of AT-III with key molecular targets in the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathway. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence assays were employed to detect the expression levels of Raf, MEK1/2, ERK1, IκBβ, IKKβ, and NF-κB in rat gastric tissues to verify the effects of AT-III on IND-induced GU and MAPK/NF-κB-mediated inflammatory responses.

Results

Histological and ultrastructural analyses revealed significant improvements in rat gastric mucosa following AT-III treatment. Molecular docking indicated strong binding affinity of AT-III to MAPK/NF-κB pathway targets. Subsequent qRT-PCR and immunofluorescence experiments confirmed these findings, demonstrating that AT-III downregulated mRNA and protein expressions of Raf, MEK1/2, ERK1, IκBβ, IKKβ, and NF-κB in rats.

Conclusion

By inhibiting pivotal regulators within the MAPK/NF-κB signaling cascade, AT-III effectively reduced local inflammation, ameliorated the pathological morphology of IND-induced GU in rats, and enhanced therapeutic outcomes, indicating its potential as a therapeutic agent for GU.