Gentisic acid attenuates ovalbumin-induced airway inflammation, oxidative stress, and ferroptosis through the modulation of Nrf2/HO-1 and NF-κB signaling pathways.

Autor: Abdelmawgood IA; Zoology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Kotb MA; Zoology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Hassan HS; Faculty of Pharmacy, Tanta University, 31527 Tanta, Egypt., Mahana NA; Zoology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Rochdi AM; Biotechnology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Sayed NH; Biotechnology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Elsafoury RH; Biotechnology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Saber AM; Biotechnology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Youssef MN; Biotechnology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Waheeb NG; Biotechnology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt., Al-Rifai MWA; Al-Makassed Islamic Charitable, East Jerusalem, Biet Jala Hospital, Biet Jala, Palestine., Badr AM; Zoology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt. Electronic address: abeerbadr@cu.edu.eg., Abdelkader AE; Zoology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 16; Vol. 146, pp. 113764. Date of Electronic Publication: 2024 Dec 16.
DOI: 10.1016/j.intimp.2024.113764
Abstrakt: Asthma, a lung disorder that causes impaired respiratory function, is characterized by an apparent infiltration of inflammatory cells. Gentisic acid (GA), a phenolic acid common in food ingredients, has antioxidant, antibacterial, and anti-inflammatory properties. Its potential application in mitigating asthma, however, remains unexplored. The current investigation studies GA's therapeutic potential for allergic asthma. BALB/c mice were challenged and sensitized to ovalbumin (OVA) to establish the animal model. We investigated how GA affected asthmatic behavior, leukocyte infiltration, histopathological alterations, oxidative stress, immunoglobulin E (IgE) production, and airway inflammation. ELISA and immunohistochemistry (IHC) techniques were employed to measure Nrf2, HO-1, and NF-κB's expression. To investigate the protein-ligand interaction between GA and Keap1, molecular docking analysis was utilized. The GA treatment significantly reduced nasal scratching, oxidative stress in the lungs, the infiltration of inflammatory cells, IgE content, iron accumulation, and NF-κB activation. It also upregulated Nrf2 and HO-1. Additionally, in silico studies revealed GA and Keap1 binding to activate Nrf2 by disrupting the Keap1-Nrf2 interaction. The study at hand is the first to investigate and report on the immunomodulatory impacts of GA on induced asthma in BALB/c mice. Our findings reveal that GA can be utilized as an anti-asthmatic agent via Nrf2/HO-1 and NF-κB pathway regulation.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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