Interplay of Biochemical, Genetic, and Immunohistochemical Factors in the Etio-Pathogenesis of Gastric Ulcer in Rats: A Comparative Study of the Effect of Pomegranate Loaded Nanoparticles Versus Pomegranate Peel Extract

Nessren M Abd El-Rady; Marwa A Dahpy; Amel Ahmed; Dalia A Elgamal; Safy Hadiya; Mai A M Ahmed; Zain El-Abdeen Ahmed Sayed; Doaa Abdeltawab; Ahmed Shawkat Abdelmohsen; Alshaimaa Abdelkhaliq Mohammad Farrag; Ahmed M Ashmawy; Marwa K Khairallah; Heba M Galal

doi:10.3389/fphys.2021.649462

Interplay of Biochemical, Genetic, and Immunohistochemical Factors in the Etio-Pathogenesis of Gastric Ulcer in Rats: A Comparative Study of the Effect of Pomegranate Loaded Nanoparticles Versus Pomegranate Peel Extract

Front Physiol. 2021 Mar 23:12:649462. doi: 10.3389/fphys.2021.649462. eCollection 2021.

Authors

Affiliations

¹ Medical Physiology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
² Medical Physiology Department, Sphinx University, New Assiut, Egypt.
³ Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁴ Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁵ Assiut International Center of Nanomedicine, Al-Rajhy Liver Hospital, Assiut University, Assiut, Egypt.
⁶ Department of Pharmcognosy and Natural Products Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
⁷ Department of Internal Medicine and Gastroenterology, Gastroenterology and Hepatology Unit, Assiut University Hospital, Assiut, Egypt.
⁸ Tropical Medicine and Gastroenterology Department, Alrajhi Hospital, Assiut University, Assiut, Egypt.
⁹ Department of Anatomy, College of Medicine, University of Bisha, Bisha, Saudi Arabia.
¹⁰ Nephrology and Internal Medicine, Assiut University, Faculty of Medicine, Assiut University, Assiut, Egypt.
¹¹ Department of Medical Physiology, College of Medicine, Jouf University, Sakaka, Saudi Arabia.

Abstract

Background: Few data are available about the role of herbal extract loaded nanoparticles as an alternative safe medicine for the management of a gastric ulcer.

Aim: This work is targeted at exploring the physiological effects of pomegranate loaded nanoparticles (PLN) against an indomethacin IND-induced gastric ulcer and comparing the results with traditional pomegranate peel extract (PPE).

Methods: Twenty-four rats were equally distributed into four groups: control, IND-treated, PLN-treated, and PPE-treated groups. Gross examination of gastric mucosa, and the calculation of ulcer and inhibition indices were done. Serum malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin 2 (IL-2), IL-6, IL-10, gastric homogenate prostaglandin E₂ (PGE₂), and nitric oxide (NO) were estimated. Mucosal endothelial nitric oxide synthase (eNOS mRNA) expression was identified by qPCR. Histological and immuno-histochemical staining of Tumor necrosis factor-α (TNF-α) and eNOS of stomach mucosa were performed.

Results: In comparison with the control group, IND-treated rats showed visible multiple ulcers with ulcer index, serum MDA, IL-2 and IL-6 were elevated while IL-10, PGE₂, NO, and eNOS mRNA expression were significantly reduced. Damaged surface epithelium with disrupted glandular architecture and heavy leucocyte infiltration of lamina propria was noticed. Immunohistochemical staining of stomach mucosa revealed marked increased TNF-α and reduced eNOS. Oral administration of PLN and PPE succeeded in improving the gross mucosal picture, and all biochemical, histological, and immunohistochemical alterations.

Conclusion: Both PLN and PPE potently alleviated IND-induced gastric ulceration via increasing TAC, PGE₂, NO, eNOS mRNA, and protein expression. However, the healing effect of PLN was obviously greater than PPE-treated rats.

Keywords: IL; IND-induced gastric ulcer; PGE2; TAC; TNF-α; nitric oxide; pomegranate loaded nanoparticles.