PMID- 36403646 OWN - NLM STAT- MEDLINE DCOM- 20221212 LR - 20221212 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 311 IP - Pt B DP - 2022 Dec 15 TI - Targeting endoplasmic reticulum stress, Nrf-2/HO-1, and NF-kappaB by myristicin and its role in attenuation of ulcerative colitis in rats. PG - 121187 LID - S0024-3205(22)00887-6 [pii] LID - 10.1016/j.lfs.2022.121187 [doi] AB - AIMS: Ulcerative colitis (UC) is characterized by the up-regulation of pro-inflammatory mediators, apoptotic signals, and oxidative stress that can lead to an increased risk of colorectal cancer. The present study aims to investigate the possible role of myristicin in modulating endoplasmic reticulum stress (ERS) and risk-associated conditions in acetic acid (AA)-induced UC. MATERIALS AND METHODS: Adult male rats were treated with 150 mg/kg body weight of myristicin or mesalazine orally either as pre/post treatment or post-treatment only. The gene expression of glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and nuclear factor kappa B (NF-kappaB), percentage of DNA fragmentation, and serum levels of some oxidative and inflammatory markers were measured. KEY FINDINGS: The results indicated the potential upregulation of ERS, pro-apoptotic, lipid peroxidation, and pro-inflammatory cascades by induction of UC in rats. However, myristicin could effectively reverse the deteriorated effects of ulceration in colonic mucosa. It was mediated through downregulation of the ERS markers GRP78 and CHOP genes expression, reduction of NF-kappaB mRNA expression, DNA fragmentation, reduced lipid peroxidation, myeloperoxidase (MPO) activity and pro-inflammatory markers (Tumor necrosis factor-alpha (TNF-alpha), Interleukin-1beta (IL-1beta) and cyclo‑oxygenase (COX-2) activity). Accompanied by elevated levels of IL-10, colonic Nuclear erythroid factor (Nrf-2) and Heme oxygenase (HO-1) activity as well as blood antioxidant enzymes activity. Results of docking might confirm the biological results of our study. SIGNIFICANCE: Myristicin could effectively modulate important stress, and inflammatory effectors and protect mucosal DNA from oxidative damage which can serve as a promising candidate for the treatment of ulcerative colitis. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Ismail Abo El-Fadl, Huda M AU - Ismail Abo El-Fadl HM AD - Biochemistry and Nutrition Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt. Electronic address: huda.mohamad@women.asu.edu.eg. FAU - Mohamed, Mamdouh F A AU - Mohamed MFA AD - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524 Sohag, Egypt. LA - eng PT - Journal Article DEP - 20221117 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Allylbenzene Derivatives) RN - 0 (Antioxidants) RN - EC 1.14.14.18 (Hmox1 protein, rat) RN - 04PD6CT78W (myristicin) RN - 0 (NF-kappa B) RN - 0 (Nfe2l2 protein, rat) SB - IM MH - Animals MH - Male MH - Rats MH - *Allylbenzene Derivatives MH - Antioxidants/pharmacology MH - *Colitis, Ulcerative/chemically induced/drug therapy/metabolism MH - Endoplasmic Reticulum Stress MH - NF-kappa B/metabolism OTO - NOTNLM OT - Colitis OT - DNA damage OT - ER-stress OT - Myristicin OT - NF-kappaB OT - Nrf-2/HO-1 COIS- Declaration of competing interest No potential conflict of interest was reported by the author. EDAT- 2022/11/21 06:00 MHDA- 2022/11/30 06:00 CRDT- 2022/11/20 19:22 PHST- 2022/07/27 00:00 [received] PHST- 2022/10/15 00:00 [revised] PHST- 2022/11/08 00:00 [accepted] PHST- 2022/11/21 06:00 [pubmed] PHST- 2022/11/30 06:00 [medline] PHST- 2022/11/20 19:22 [entrez] AID - S0024-3205(22)00887-6 [pii] AID - 10.1016/j.lfs.2022.121187 [doi] PST - ppublish SO - Life Sci. 2022 Dec 15;311(Pt B):121187. doi: 10.1016/j.lfs.2022.121187. Epub 2022 Nov 17.