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Updated: Sep 9, 2025

Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
Published on: April 11, 2012
Apigenin mitigates intestinal barrier dysfunction in sepsis by modulating the AKT signaling pathway
Zheng Lijun1, Wang Liping2, Zhao Dandan3
1Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, 350122, China.
Abstract:
Sepsis is a systemic inflammatory response syndrome triggered by infection, which can lead to multiple organ dysfunction. This study untangles the synergistic multi-mechanistic effects of the natural flavonoid apigenin in ameliorating this pathological process. Utilizing a murine sepsis model and Caco-2 cell line, we systematically investigated the impact of apigenin on intestinal barrier function. Apigenin treatment (50 mg/kg) markedly improved intestinal barrier integrity, as shown by reduced serum FITC-dextran levels and restored expression of tight junction proteins Occludin, Claudin-1, and ZO-1. The compound simultaneously attenuated systemic inflammation by lowering IL-6 and TNF-α levels. Network pharmacology and molecular docking identified AKT1 and MMP-9 as key molecular targets of apigenin, which was experimentally validated through observed suppression of MMP-9 and COX-2 protein expression. These results demonstrate apigenin's capacity to preserve intestinal barrier function during sepsis through coordinated anti-inflammatory and barrier-repair mechanisms.
Insights
Apigenin, a natural flavonoid, protects against sepsis by strengthening the intestinal barrier and reducing inflammation. This study reveals its potential to combat sepsis-induced organ damage.
Area of Science:
- Biomedical Science
- Pharmacology
- Immunology
Background:
- Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, leading to organ dysfunction.
- The intestinal barrier is crucial for maintaining homeostasis, and its compromise is a hallmark of sepsis.
- Natural compounds offer potential therapeutic avenues for managing sepsis.
Purpose of the Study:
- To investigate the protective effects of apigenin on intestinal barrier function during sepsis.
- To elucidate the underlying anti-inflammatory and barrier-protective mechanisms of apigenin.
- To identify key molecular targets of apigenin in the context of sepsis.
Main Methods:
- A murine model of sepsis and Caco-2 cell line were utilized.
- Apigenin treatment effects on intestinal permeability (FITC-dextran assay) and tight junction protein expression were assessed.
- Systemic inflammatory markers (IL-6, TNF-α) and key protein targets (MMP-9, COX-2) were quantified.
Main Results:
- Apigenin treatment significantly improved intestinal barrier integrity.
- Apigenin reduced serum levels of pro-inflammatory cytokines IL-6 and TNF-α.
- Apigenin suppressed MMP-9 and COX-2 expression, targeting AKT1 and MMP-9.
Conclusions:
- Apigenin effectively preserves intestinal barrier function during sepsis.
- Apigenin exerts its protective effects through combined anti-inflammatory and barrier repair mechanisms.
- Apigenin demonstrates therapeutic potential for sepsis management.
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