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Polymethoxyflavone Apigenin-Trimethylether Suppresses LPS-Induced Inflammatory Response in Nontransformed Porcine
Orsolya Farkas1, Orsolya Palócz1, Erzsébet Pászti-Gere1
1Department of Pharmacology and Toxicology, Faculty of Veterinary Science, Szent István University, István utca 2, Budapest 1078, Hungary.
Abstract:
The in vitro anti-inflammatory effect of apigenin and its trimethylated analogue (apigenin-trimethylether) has been investigated in order to evaluate whether these flavonoids could attenuate LPS-induced inflammation in IPEC-J2 non-transformed intestinal epithelial cells. Levels of IL-6, IL-8, TNF-α, and COX-2 mRNA were measured as a marker of inflammatory response. The extracellular H2O2 level in IPEC-J2 cells was also monitored by Amplex Red assay. Our data revealed that both compounds had significant lowering effect on the inflammatory response. Apigenin (at 25 μM) significantly decreased gene expression of IL-6 in LPS-treated cells, while apigenin-trimethylether in the same concentration did not influence IL-6 mRNA level. Both apigenin and apigenin-trimethylether reduced IL-8 gene expression significantly. TNF-α mRNA level was decreased by apigenin-trimethylether, which was not influenced by apigenin. Treatment with both flavonoids caused significant reduction in the mRNA level of COX-2, but the anti-inflammatory effect of the methylated analogue was more effective than the unmethylated one. Furthermore, both flavonoids reduced significantly the level of extracellular H2O2 compared to the control cells. In conclusion, the methylated apigenin analogue could avoid LPS-induced intestinal inflammation and it could be applied in the future as an effective anti-inflammatory compound.
Insights
Apigenin and its methylated form reduce inflammation in intestinal cells. The methylated analogue, apigenin-trimethylether, shows greater effectiveness in mitigating lipopolysaccharide-induced inflammation and reducing inflammatory markers.
Area of Science:
- Cell Biology
- Pharmacology
- Immunology
Background:
- Flavonoids, like apigenin, possess anti-inflammatory properties.
- Intestinal inflammation, often triggered by lipopolysaccharide (LPS), impacts epithelial cell function.
- Investigating novel anti-inflammatory compounds is crucial for gut health.
Purpose of the Study:
- To evaluate the in vitro anti-inflammatory effects of apigenin and apigenin-trimethylether.
- To determine if these flavonoids can attenuate LPS-induced inflammation in intestinal epithelial cells (IPEC-J2).
- To compare the efficacy of apigenin and its methylated analogue in reducing inflammatory markers.
Main Methods:
- Utilized IPEC-J2 cells to model intestinal inflammation.
- Administered apigenin and apigenin-trimethylether to LPS-treated cells.
- Measured mRNA levels of inflammatory markers: IL-6, IL-8, TNF-α, and COX-2.
- Assessed extracellular hydrogen peroxide (H2O2) levels using the Amplex Red assay.
Main Results:
- Both apigenin and apigenin-trimethylether significantly reduced IL-8 gene expression.
- Apigenin-trimethylether effectively decreased TNF-α mRNA levels, unlike apigenin.
- Both compounds significantly lowered COX-2 mRNA levels, with the methylated analogue showing greater efficacy.
- Apigenin (25 μM) reduced IL-6 mRNA, while apigenin-trimethylether did not at this concentration.
- Both flavonoids significantly reduced extracellular H2O2 levels.
Conclusions:
- Apigenin-trimethylether demonstrates significant potential in preventing LPS-induced intestinal inflammation.
- The methylated apigenin analogue may serve as a future therapeutic agent for inflammatory conditions.
- Flavonoids, particularly methylated derivatives, warrant further investigation for their anti-inflammatory applications in the gut.
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