PMID- 37623736 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20230829 IS - 1660-3397 (Electronic) IS - 1660-3397 (Linking) VI - 21 IP - 8 DP - 2023 Aug 18 TI - Echinochrome Ameliorates Physiological, Immunological, and Histopathological Alterations Induced by Ovalbumin in Asthmatic Mice by Modulating the Keap1/Nrf2 Signaling Pathway. LID - 10.3390/md21080455 [doi] LID - 455 AB - Asthma is a persistent inflammatory disease of the bronchi characterized by oxidative stress, airway remodeling, and inflammation. Echinochrome (Ech) is a dark-red pigment with antioxidant and anti-inflammatory activities. In this research, we aimed to investigate the effects of Ech against asthma-induced inflammation, oxidative stress, and histopathological alterations in the spleen, liver, and kidney in mice. Mice were divided into four groups (n = 8 for each): control, asthmatic, and asthmatic mice treated intraperitoneally with 0.1 and 1 mg/kg of Ech. In vitro, findings confirmed the antioxidant and anti-inflammatory activities of Ech. Ech showed antiasthmatic effects by lowering the serum levels of immunoglobulin E (IgE), interleukin 4 (IL-4), and interleukin 1beta (IL-1beta). It attenuated oxidative stress by lowering malondialdehyde (MDA) and nitric oxide (NO) contents and increasing reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-s-transferase (GST), and catalase (CAT) in the liver, spleen, and kidney. Moreover, it protected asthma-induced kidney and liver functions by increasing total protein and albumin and decreasing aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, urea, and uric acid levels. Additionally, it ameliorated histopathological abnormalities in the lung, liver, spleen, and kidney. Additionally, molecular docking studies were used to examine the interactions between Ech and Kelch-like ECH-associated protein 1 (Keap1). PCR and Western blot analyses confirmed the association of Ech with Keap1 and, consequently, the regulatory role of Ech in the Keap1-(nuclear factor erythroid 2-related factor 2) Nrf2 signaling pathway in the liver, spleen, and kidney. According to our findings, Ech prevented asthma and its complications in the spleen, liver, and kidney. Inhibition of inflammation and oxidative stress are two of echinochrome's therapeutic actions in managing asthma by modulating the Keap1/Nrf2 signaling pathway. FAU - Abdelmawgood, Islam Ahmed AU - Abdelmawgood IA AD - Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt. FAU - Mahana, Noha Ahmed AU - Mahana NA AUID- ORCID: 0000-0001-7905-7787 AD - Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt. FAU - Badr, Abeer Mahmoud AU - Badr AM AD - Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt. FAU - Mohamed, Ayman Saber AU - Mohamed AS AD - Zoology Department, Faculty of Science, Cairo University, Giza 12613, Egypt. FAU - Al Shawoush, Abdeljalil Mohamed AU - Al Shawoush AM AD - Zoology Department, Faculty of Science, Sirte University, Sirte 128123, Libya. FAU - Atia, Tarek AU - Atia T AD - Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia. FAU - Abdelrazak, Amir Elhadi AU - Abdelrazak AE AD - Department of Medical Physiology, Medicine Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia. FAU - Sakr, Hader I AU - Sakr HI AUID- ORCID: 0000-0003-2917-2423 AD - Department of Medical Physiology, Medicine Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia. AD - Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt. LA - eng PT - Journal Article DEP - 20230818 PL - Switzerland TA - Mar Drugs JT - Marine drugs JID - 101213729 RN - 9006-59-1 (Ovalbumin) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Antioxidants) RN - 0 (Keap1 protein, mouse) SB - IM MH - Animals MH - Mice MH - Ovalbumin MH - Kelch-Like ECH-Associated Protein 1 MH - *NF-E2-Related Factor 2 MH - Antioxidants/pharmacology MH - Molecular Docking Simulation MH - *Asthma/drug therapy MH - Signal Transduction MH - Inflammation PMC - PMC10455754 OTO - NOTNLM OT - Keap1 OT - Nrf2 OT - asthma OT - echinochrome OT - inflammation OT - ovalbumin OT - oxidative stress COIS- The authors declare no conflict of interest. EDAT- 2023/08/25 12:42 MHDA- 2023/08/28 06:42 PMCR- 2023/08/18 CRDT- 2023/08/25 09:15 PHST- 2023/07/22 00:00 [received] PHST- 2023/08/15 00:00 [revised] PHST- 2023/08/16 00:00 [accepted] PHST- 2023/08/28 06:42 [medline] PHST- 2023/08/25 12:42 [pubmed] PHST- 2023/08/25 09:15 [entrez] PHST- 2023/08/18 00:00 [pmc-release] AID - md21080455 [pii] AID - marinedrugs-21-00455 [pii] AID - 10.3390/md21080455 [doi] PST - epublish SO - Mar Drugs. 2023 Aug 18;21(8):455. doi: 10.3390/md21080455.