In vivo anti-gastric ulcer activity of 7-O-methyl aromadendrin and sakuranetin via mitigating inflammatory and oxidative stress trails.

Autor: Ali DE; Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt., El-Shiekh RA; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. Electronic address: riham.adel@pharma.cu.edu.eg., El Sawy MA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt., Khalifa AA; Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt., Elblehi SS; Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt., Elsokkary NH; Department of Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt., Ali MA; Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Dec 05; Vol. 335, pp. 118617. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1016/j.jep.2024.118617
Abstrakt: Ethnopharmacological Relevance: Eucalyptus genus has been used for a very long time in conventional treatment as an anti-ulcer remedy.
Aim of the Study: The study aimed to explore the gastroprotective potential of 7-O-methyl aromadendrin (7-OMA), and sakuranetin (SKN) in comparison with omeprazole. The study tackled the contribution of their anti-inflammatory, antioxidant, and antiapoptotic capabilities to their anti-gastric ulcer effects.
Materials and Methods: An ethanol-induced gastric ulcer model in rats was adopted and the consequences were confirmed by a molecular docking study.
Results: The oral pretreatment of rats 1 h before ethanol using omeprazole (20 mg/kg) or 7-OMA (20 or 40 mg/kg) or SKN (20 or 40 mg/kg) exhibited gastroprotective and anti-inflammatory properties to different extents. These amendments witnessed as restorations in the stomach histological architecture in H and E-stained sections, mucus content in periodic acid-Schiff (PAS) stained sections with increased cellular proliferation, as demonstrated by increased immunohistochemical staining of PCNA, and increments in stomach COX-1 activity and eNOS. The highest dose of SKN showed the best corrections to reach 4.8, 1.8, and 2.1 folds increase in PAS, COX-1 and eNOS, respectively as compared to the untreated ethanol-induced gastric ulcer group; effects that were comparable to that of omeprazole. Moreover, reductions in COX-2 activity, and the protein expression of NF-κB, IL-6, TNF-α and NOx, in addition to the gene expression of inducible iNOS were also noted. Moreover, the antioxidant and antiapoptotic capabilities of omeprazole, 7-OMA, and SKN were perceived. SKN (40 mg/kg) succeeded to show the unsurpassed results to reach 293.6%, 237.1%, 274.7%, 248.2%, and 175.4% in total and reduced GSH, catalase, SOD, and Bcl2, respectively, as well as 50.0%, 46.8%, and 52.1 % in oxidized GSSG, TBARS and caspase-3, respectively. The gastroprotective potential of the tested compounds can be assigned to their anti-inflammatory, antioxidant and antiapoptotic properties.7-OMA and SKN were studied using molecular docking into the binding sites of the most significant inflammatory targets, including COX-2, TNF-α, iNOS, and NF-κB. Pharmacokinetic and physicochemical parameters in silico were appropriate.
Conclusion: The prophylactic use of 7-OMA and SKN could be considered as an add-on to recurrent gastric ulcers and might influence its therapeutic approaches.
Competing Interests: Declaration of Competing interest We wish to confirm that there are no known conflicts of interest associated with this publication of “In vivo antiulcer activity of 7-O-methyl aromadendrin and sakuranetin isolated from Eucalyptus torquata L. via mitigating inflammatory and oxidative stress trails.” to be published in Journal of Ethnopharmacology. With the submission of this manuscript, I would like to undertake that the above-mentioned manuscript has not been published elsewhere, accepted for publication elsewhere or under editorial review for publication elsewhere; and that my Institute's (Faculty of Pharmacy, Cairo University) representative is fully aware of this submission.
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Databáze: MEDLINE