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Published on: July 27, 2022
Minocycline synergizes with corticosteroids in reducing colitis severity in mice via the modulation of
Maitham A Khajah1, Sanaa Hawai1, Ahmad Barakat1
1College of Pharmacy, Kuwait University, Kuwait City, Kuwait.
Abstract:
Background: A few studies have highlighted the anti-inflammatory properties of minocycline in reducing colitis severity in mice, but its molecular mechanism is not fully understood. The aim of this study was to determine the anti-inflammatory properties of minocycline and the expression/activity profiles of molecules involved in pro-inflammatory signaling cascades, cytokines, and molecules involved in the apoptotic machinery. The synergistic effect between minocycline and corticosteroids was also evaluated. Methods: The effects of various treatment approaches were determined in mice using the dextran sulfate sodium (DSS) colitis model at gross and microscopic levels. The expression/activity profiles of various pro- or anti-inflammatory molecules were determined using Western blotting and polymerase chain reaction (PCR). Results: Minocycline treatment significantly reduced colitis severity using prophylactic and treatment approaches and produced a synergistic effect with budesonide and methylprednisolone in reducing the active state of colitis. This was mediated in part through reduced colonic expression/activity of pro-inflammatory molecules, cytokines, proteins involved in the apoptotic machinery, and increased expression of the anti-inflammatory cytokine IL-10. Conclusion: Minocycline synergizes with corticosteroids to reduce colitis severity, which could reduce their dose-dependent side effects and treatment cost. The reduction in colitis severity was achieved by modulating the expression/activity profiles of various pro- and anti-inflammatory signaling molecules, cytokines, and molecules involved in the apoptotic machinery.
Insights
Minocycline reduces colitis severity in mice by modulating inflammatory and apoptotic pathways. It also enhances corticosteroid effectiveness, potentially lowering required doses and treatment costs.
Area of Science:
- Immunology
- Pharmacology
- Gastroenterology
Background:
- Limited understanding of minocycline's molecular mechanisms in reducing colitis.
- Previous studies suggest anti-inflammatory effects of minocycline in murine colitis models.
Purpose of the Study:
- To elucidate the anti-inflammatory properties and molecular mechanisms of minocycline in colitis.
- To evaluate the synergistic effects of minocycline with corticosteroids.
Main Methods:
- Dextran sulfate sodium (DSS) induced colitis model in mice.
- Assessment of colitis severity at gross and microscopic levels.
- Analysis of pro-inflammatory/anti-inflammatory molecules and apoptotic markers via Western blotting and PCR.
Main Results:
- Minocycline significantly reduced colitis severity both prophylactically and therapeutically.
- Minocycline demonstrated synergistic effects with budesonide and methylprednisolone.
- Treatment modulated colonic expression of pro-inflammatory and apoptotic molecules, while increasing IL-10.
Conclusions:
- Minocycline synergizes with corticosteroids to ameliorate colitis, potentially reducing side effects and costs.
- The therapeutic effects are linked to modulation of inflammatory signaling, cytokine profiles, and apoptotic pathways.
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