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Published on: January 5, 2017
Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between
Ahmed M Kabel1, Aliaa Atef2, Hany M Borg3
1Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
Abstract:
Colitis is one of the inflammatory states that affect the intestinal wall and may even predispose to malignancy due to chronic irritation. Although the etiology of colitis is not yet fully explored, a combination of genetic and environmental factors is strongly incriminated. Perindopril is an angiotensin-converting enzyme inhibitor that is used for the management of a wide range of cardiovascular diseases. Ambrosin is a sesquiterpene lactone that was proven to have beneficial effects in disorders characterized by inflammatory nature. The objective of this study is to make a comparison between the effects of perindopril or ambrosin on dextran sulfate sodium (DSS)-induced colitis in mice and to explore the effect of their combination. The present findings indicate that each ambrosin or perindopril alone or in combination is able to ameliorate oxidative stress and suppress the proinflammatory pathways in the colonic tissues of DSS-treated mice via mechanisms related to toll-like receptor 4/nuclear factor kappa B signaling and modulation of peroxisome proliferator-activated receptor gamma/sirtuin-1 levels. In addition, each ambrosin or perindopril alone or in combination inhibits apoptosis and augments the mediators of autophagy in DSS-treated mice. These effects are reflected in the amelioration of the histopathological and electron microscopic changes in the colonic tissues. Interestingly, the most remarkable effects are those encountered with the perindopril/ambrosin combination compared to the groups treated with each of these agents alone. In conclusion, the perindopril/ambrosin combination might represent an effective modality for mitigation of the pathogenic events and the clinical sequelae of colitis.
Insights
The combination of perindopril and ambrosin effectively reduces inflammation and oxidative stress in colitis models. This novel combination shows promising therapeutic potential for mitigating colitis symptoms and associated pathological changes.
Area of Science:
- Gastroenterology
- Pharmacology
- Immunology
Background:
- Colitis is an inflammatory condition of the intestinal wall, potentially linked to chronic irritation and malignancy.
- The exact causes of colitis are unknown but likely involve genetic and environmental factors.
- Perindopril (ACE inhibitor) and ambrosin (anti-inflammatory sesquiterpene lactone) have demonstrated therapeutic potential.
Purpose of the Study:
- To compare the effects of perindopril and ambrosin, individually and in combination, on dextran sulfate sodium (DSS)-induced colitis in mice.
- To investigate the underlying mechanisms of action for these agents in colitis.
Main Methods:
- Induction of colitis in mice using dextran sulfate sodium (DSS).
- Administration of perindopril, ambrosin, or their combination to DSS-treated mice.
- Assessment of oxidative stress, inflammatory pathways (TLR4/NF-κB), apoptosis, autophagy, and histopathological changes in colonic tissues.
Main Results:
- Both perindopril and ambrosin, alone or combined, ameliorated oxidative stress and suppressed pro-inflammatory pathways in DSS-induced colitis.
- Treatment inhibited apoptosis and augmented autophagy mediators in colonic tissues.
- The combination of perindopril and ambrosin demonstrated the most significant therapeutic effects compared to individual treatments.
Conclusions:
- The perindopril/ambrosin combination effectively mitigates DSS-induced colitis in mice.
- This combination ameliorates oxidative stress, suppresses inflammation, inhibits apoptosis, and modulates autophagy.
- Perindopril and ambrosin combination therapy holds promise for managing colitis pathogenesis and clinical outcomes.

