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Papers of the Week

2022 Aug 27

Basic Clin Pharmacol Toxicol

The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP-1α/miR-143 signalling.


Bagalagel A, Diri R, Noor A, Almasri D, Bakhsh HT, Kutbi HI, Al-Gayyar MMH
Basic Clin Pharmacol Toxicol. 2022 Aug 27.
PMID: 36029292.


Patients with ulcerative colitis (UC) experience diarrhoea, hematochezia, and abdominal pain. UC is a well-known health challenge affecting 200-250 per 100,000 individuals worldwide, with a similar prevalence in both sexes and elevated upon activation of gut immune responses. We evaluated the potential therapeutic effects of cycloastragenol in experimentally-induced UC rats and examined the modulation of sphingosine kinase (SphK), macrophage inflammatory protein (MIP)-1α, and miR-143. We treated UC rats with 30 mg/kg cycloastragenol and assessed gene and protein expression levels of SphK, MIP-1α, B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), miR-143, NF-κB, tumour necrosis factor (TNF)-α, and active caspase-3. Colon sections were examined using electron microscopy; additional sections were stained with hematoxylin-eosin or immunostained with anti-TNF-α and anti-caspase-3 antibodies. Electron microscopy of UC specimens revealed dark distorted goblet cell nuclei with disarranged mucus granules and a non-distinct brush border with atypical microvilli. Hematoxylin-eosin staining showed damaged intestinal glands, severe hemorrhage, and inflammatory cell infiltration. Cycloastragenol treatment improved the induced morphological changes. In UC rats, cycloastragenol significantly reduced expression levels of SphK, MIP-1α, BAX, NF-κB, TNF-α, and active caspase-3, associated with BCL2 and miR-143 overexpression. Therefore, cycloastragenol protects against UC by modulating SphK/MIP-1α/miR-143, subsequently deactivating inflammatory and apoptotic pathways.