Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between Toll-Like Receptor 4, the Pro-Inflammatory Pathways, and SIRT1/PPAR-γ Signaling

  • Pharmaceuticals (Basel). 2022 May 13;15(5):600. doi: 10.3390/ph15050600.
Ahmed M Kabel  1 ,  Aliaa Atef  2 ,  Hany M Borg  3 ,  Azza A K El-Sheikh  4 ,  Hana J Al Khabbaz  5 ,  Hany H Arab  6 ,  Remon S Estfanous  7
Affiliations
  • 1. Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
  • 2. Department of Pathology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
  • 3. Physiology Department, Faculty of Medicine, Kafrelsheikh University, Kafr El-Shaikh 33516, Egypt.
  • 4. Basic Health Sciences Department, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
  • 5. Biochemistry Division, College of Pharmacy, Riyadh Elm University, Riyadh 11681, Saudi Arabia.
  • 6. Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
  • 7. Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
PMID: 35631426 DOI: 10.3390/ph15050600
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.

Keywords
ambrosin; colitis; dextran sulfate sodium; inflammation; mice; perindopril.
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