Dihydroartemisinin attenuates acetic acid-induced ulcerative colitis in rats: Suppression of inflammation and modulation of NFκβ/TNF-α/RIPK1-mediated necroptosis and apoptosis

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-02-15 DOI:10.1016/j.tice.2025.102791

Mamdouh Eldesoqui , Lashin S. Ali , Omnia S. Erfan , Amal F. Dawood , Abdelnaser A. Badawy , Sahar K. Ali , Zeinab A. Mohammed , Alia Mohamed Mahmoud , Eman M. Embaby , Eman Mohamad El Nashar , Majed Aldehri , Hind Zafrah , Norah Saeed Al-Zahrani , Rania Hassan Mohamed Soliman

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引用次数: 0

Abstract

Background

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by the overproduction of reactive oxygen species (ROS) and the release of inflammatory mediators. Dihydroartemisinin (DHA) is a semi-synthetic active metabolite of artemisinin that has anti-inflammatory, antioxidant, and anti-fibrotic properties.

Objective

This study aimed to assess the therapeutic benefits of DHA on acetic acid(AA) -induced UC in rats, with particular emphasis on its anti-inflammatory effects and its influence on NFκB/TNF-α/RIPK1 necroptotic pathways.

Methods

Eighteen rats were allocated into control, acetic acid-induced colitis (AA), and DHA-treated (AA+DHA) groups. Colitis was caused by rectal instillation of 5 % acetic acid. DHA was supplied via intraperitoneal injection. Histological, biochemical studies of oxidative stress, inflammatory and anti-inflammatory mediators, Western blotting for TNF-α, RIPK1, and caspase 3, and immunohistochemical assessment of NFκB, TNF-α, and RIPK1, were conducted.

Results

DHA treatment markedly diminished macroscopic damage, disease activity index, histopathology scores, and malondialdehyde (MDA) levels, enhancing glutathione (GSH) levels. Additionally, DHA decreased serum TNF-α and IL-6 and increased IL-10. Western blotting and immunohistochemistry investigations validated the reduced expression of TNF-α, RIPK1, and caspase 3 in DHA-treated rats.

Conclusion

DHA demonstrates protective properties against acetic acid-induced UC by decreasing oxidative stress and inflammation, modifying TNF-α activity to regulate apoptotic and necroptotic pathways. So, DHA may be a favorable therapeutic alternative for the management of ulcerative colitis.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.