Syzygium samarangense leaf extract mitigates indomethacin-induced gastropathy via the NF-κB signaling pathway in rats
Affiliations
Affiliations
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt. Electronic address: mfabdelaziz@zu.edu.eg.
- Pharmaceutical and Fermentation Industries Development Center (PFIDC), City of Scientific Research and Technological Applications (SRTA-City), New Borg El-Arab, Alexandria 21934, Egypt; Pharmacology department, Faculty of Pharmacy, Deraya University, New Mina, PO 61768, Egypt.
- Department of Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El Sheikh 33516, Egypt.
- College of Engineering and Technology, American University of the Middle East, Kuwait.
- Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
- African Sustainable Agriculture Research Institute (ASARI), Mohammed VI Polytechnic University (UM6P), Laâyoune, Morocco.
- AgroBioSciences, Mohammed VI Polytechnic University, Lot 660, Hay Moulay Rachid, Ben-Guerir 43150, Morocco. Electronic address: mansour.sobeh@um6p.ma.
Abstract
We previously profiled the chemical composition of wax apple, Syzygium samarangense, leaf extract using HR-LC-MS/MS and reported its antioxidant, hepatoprotective and antitrypanosomal activities. The plant is widely used in traditional medicine to cure several ailments like bronchitis, asthma, diabetes, fever, pathogenic infections, gut spasms, as well as renal diseases. However, neither the gastroprotective effects nor the underlying mechanisms were explored. Here, we investigated the gastroprotective potential of the leaf extract on indomethacin-induced gastric ulcer in rats and explored the involved mechanism(s) of action. Administration of indomethacin significantly increased the ulcer index, mucosal injury, the gastric levels of the inflammatory markers nuclear factor kabba B-p65(NF-κB p65), myeloperoxidase (MPO), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), lipid peroxidation product, malondialdehyde (MDA) and Caspase-3 expression. It reduced the gastric levels of the endogenous antioxidants glutathione as well peroxidase (GPx), reduced glutathione (GSH) and the gastric mucosal protective factors, mucus secretion and goblet cells. Pretreatment with the leaf extract displayed a prominent decrease in the ulcer index, inflammatory cell infiltration, inflammatory markers, MDA, protein expression of Caspase-3 and a significant increase in the gastric levels of the endogenous antioxidants, mucus content and goblet cell proliferation when compared to the indomethacin group. The individual secondary metabolites of the extract exhibited low binding energy when docked into the prostaglandin receptors EP3 and EP4. This study revealed the gastroprotective effect of S. samarangense on indomethacin-induced gastric ulcer in rats. The gastroprotective effects might be attributed to cytoprotective, antioxidant, anti-inflammatory and antiapoptotic activities with a possible potential of activating EP3 and EP4 receptors. In conclusion, S. samarangense has a promising potential in the prevention of NSAIDs-induced ulcers.
Keywords: Caspase-3; Gastric ulcer; MPO; NF-κB p65; Syzygium samarangense.
Similar articles
de Araújo ERD, Guerra GCB, Araújo DFS, de Araújo AA, Fernandes JM, de Araújo Júnior RF, da Silva VC, de Carvalho TG, Ferreira LS, Zucolotto SM.Int J Mol Sci. 2018 Apr 24;19(5):1265. doi: 10.3390/ijms19051265.PMID: 29695040 Free PMC article.
Bang BW, Park D, Kwon KS, Lee DH, Jang MJ, Park SK, Kim JY.J Med Food. 2019 Feb;22(2):140-151. doi: 10.1089/jmf.2018.4231. Epub 2019 Jan 24.PMID: 30676853
de Souza MC, Vieira AJ, Beserra FP, Pellizzon CH, Nóbrega RH, Rozza AL.Phytomedicine. 2019 Feb;53:37-42. doi: 10.1016/j.phymed.2018.09.027. Epub 2018 Sep 4.PMID: 30668410
Figueiredo FF, Damazo AS, Arunachalam K, Silva MJD, Pavan E, Lima JCDS, Martins DTO.J Ethnopharmacol. 2023 Jun 12;309:116338. doi: 10.1016/j.jep.2023.116338. Epub 2023 Mar 2.PMID: 36870462
Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers.
Suleyman H, Albayrak A, Bilici M, Cadirci E, Halici Z.Inflammation. 2010 Aug;33(4):224-34. doi: 10.1007/s10753-009-9176-5.PMID: 20084447 Review.
Cited by
Ferulic Acid Treats Gastric Ulcer via Suppressing Oxidative Stress and Inflammation.
Ermis A, Aritici Colak G, Acikel-Elmas M, Arbak S, Kolgazi M.Life (Basel). 2023 Jan 31;13(2):388. doi: 10.3390/life13020388.PMID: 36836745 Free PMC article.
Hassan NA, Abdelfattah MAO, Mandour YM, El-Shazly AM, Sobeh M, Mahmoud MF.Pharmaceuticals (Basel). 2022 Oct 31;15(11):1349. doi: 10.3390/ph15111349.PMID: 36355521 Free PMC article.
Wang Q, Zhan X, Wang B, Wang F, Zhou Y, Xu S, Li X, Tang L, Jin Q, Li W, Gong L, Fu A.Antioxidants (Basel). 2022 Sep 13;11(9):1799. doi: 10.3390/antiox11091799.PMID: 36139873 Free PMC article.
Abd-Eldayem AM, Alnasser SM, Abd-Elhafeez HH, Soliman SA, Abdel-Emam RA.Molecules. 2022 Aug 31;27(17):5598. doi: 10.3390/molecules27175598.PMID: 36080365 Free PMC article.
Mahmoud MF, Nabil M, Hasan RA, El-Shazly AM, El-Ansari MA, Sobeh M.Front Pharmacol. 2022 Feb 4;13:800986. doi: 10.3389/fphar.2022.800986. eCollection 2022.PMID: 35211013 Free PMC article.