Atriplex portulacoides L. derived phytochemicals mitigate acetic acid induced colitis in rats via orchestrating Nrf2/Keap1 signalling and LncRNAs gene expression
TL;DR
APME dose-dependently and significantly reduced the pro-inflammatory cytokine TNF-α, mitigated malondialdehyde levels, and restored total antioxidant capacity in colonic tissue compared to the untreated ulcerative group, demonstrating substantial improvements in colonic architecture and cellular integrity.
Abstract
This study is the first to elucidate the mechanistic actions of Atriplex portulacoides L. methanolic extract (APME) as a natural treatment of acetic acid-induced ulcerative colitis on rat model. Phytochemical metabolic profiling of APME was determined through the determination of total phenolic and flavonoid contents, alongside negative mode LC–ESI–MS/MS analysis. Furthermore, chromatographic and spectroscopic investigations were employed to fractionate and structurally characterize the metabolites present within APME fractions. The therapeutic potential of APME in UC was evaluated by integrating histological and immunohistochemical analyses. Quantification of oxidative stress, inflammation-related, and lncRNAs (FENDRR and Neat1) gene expression was established. APME was evaluated for its total phenolic content and total flavonoid content. LC–ESI–MS/MS analysis in negative ionization mode identified 35 bioactive metabolites within APME. Stigmasterol (1) and 20-Hydroxyecdysone (2) were isolated by column chromatography from the n-hexane and ethyl acetate fractions, respectively, and characterized using spectroscopic analysis. APME dose-dependently and significantly (p < 0.05) reduced the pro-inflammatory cytokine TNF-α, mitigated malondialdehyde levels, and restored total antioxidant capacity in colonic tissue compared to the untreated ulcerative group. APME`s treatments markedly upregulated the mRNA expression levels of Nrf2 and HO-1, while concurrently suppressing NF-κB mRNA expression. Also, it showed a regulatory effect on FENDRR and Neat1. Histological, immunohistochemical, and morphometric assessments further supported these findings, demonstrating substantial improvements in colonic architecture and cellular integrity. Notably, APME represents a potential antioxidant and anti-inflammatory therapeutic candidate for UC. It modulates FENDRR and Neat1, revealing promising targets for IBD therapy.