Pre-clinical studies comparing the anti-inflammatory potential of artemisinic compounds by targeting NFκB/TNF-α/NLRP3 and Nrf2/TRX pathways in Balb/C mice

Autor: Syeda Tayyaba Batool Kazmi, Humaira Fatima, Iffat Naz, Nosheen Kanwal, Ihsan-ul Haq
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 15 (2024)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2024.1352827
Popis: Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p
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