The therapeutic effects of cycloastragenol in ulcerative colitis by modulating SphK/MIP-1/miR-143 signalling
Basic & Clinical Pharmacology & Toxicology(2022)
摘要
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)-1 alpha and miR-143. We treated UC rats with 30 mg/kg cycloastragenol and assessed gene and protein expression levels of SphK, MIP-1 alpha, B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), miR-143, NF-kappa B, tumour necrosis factor (TNF)-alpha and active caspase-3. Colon sections were examined using electron microscopy; additional sections were stained with haematoxylin-eosin or immunostained with anti-TNF-alpha and anti-caspase-3 antibodies. Electron microscopy of UC specimens revealed dark distorted goblet cell nuclei with disarranged mucus granules and a nondistinct brush border with atypical microvilli. Haematoxylin-eosin staining showed damaged intestinal glands, severe haemorrhage and inflammatory cell infiltration. Cycloastragenol treatment improved the induced morphological changes. In UC rats, cycloastragenol significantly reduced expression levels of SphK, MIP-1 alpha, BAX, NF-kappa B, TNF-alpha and active caspase-3, associated with BCL2 and miR-143 overexpression. Therefore, cycloastragenol protects against UC by modulating SphK/MIP-1 alpha/miR-143, subsequently deactivating inflammatory and apoptotic pathways.
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关键词
active caspase-3,B-cell lymphoma 2 (BCL2),BCL2 associated X (BAX),macrophage inflammatory protein (MIP)-1 alpha,miR-143,nuclear factor (NF)kappa B,sphingosine kinase (SphK),tumour necrosis factor (TNF)-alpha
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