Romanian Society of Pharmaceutical Sciences

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THE THERAPEUTIC EFFECTS OF BERBERINE EXTRACT ON ULCERATIVE COLITIS IN MICE

SI LI 1, YAN SHEN 2*

1.Department of Pediatrics, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, China
2.Department of Gastroenterology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, China

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The aim of this study was to assess the effect and mechanism through which berberine extract (BBR) protects the colon mucosa mechanical barrier of mice suffering from ulcerative colitis (UC). 60 BALB/c mice were randomly divided into five groups, 12 mice per group: the normal control group (group A), the model control group (group B), the BBR low-dose group (group C - received 50 mg/kg BBR), the BBR high-dose group (group D - received 100 mg/kg BBR) and the salazosulfapyridine (SASP) positive control (group E - received 30 mg/kg SASP). The UC model was reproduced using dextran sulphate sodium (DSS). After the UC modelling, mice were treated for 7 days. The mice were observed daily for sings of morbidity and mortality along with the evaluation of disease activity index (DAI). After the last administration of the treatment, the mice were sacrificed and colon tissues were collected and stained with haematoxylin-eosin (HE) to observe pathological changes. Western Blot was used to quantify the levels of leucine-rich repeat-containing G-protein coupled receptor 5 (LGR-5) and telomerase reverse transcriptase (TERT) proteins and markers of intestinal stem cells (ISCs). The expression levels of claudin-1, occludin and zonula occludens-1 (ZO-1) were detected through immunohistochemical streptavidin peroxidase (SP) method and the expression levels of claudin-1mRNA were measured through RT-PCR method. Compared to group B, the clinical and histopathological parameters of UC mice in each experimental group improved in different degrees, and the grade of DAI, macroscopic damage index (CMDI) and tissue damage index (TDI) in group D and E dropped significantly (p < 0.01). The content of both LGR-5 and TERT proteins in colon tissue of UC mice was significantly lower than that of normal mice (p < 0.01). After BBR or SSASP treatment, the LGR-5 and TERT protein content increased compared with model control group (p < 0.05). Expression levels of claudin-1, occludin and zona occuldens proteins (ZO-1) in UC mice tissue were significantly lower than that of normal mice. Compared with group A, claudin-1 mRNA level increased in all four groups (p < 0.01). BBR has a beneficial effect on the onset and development of UC in mice. The mechanism of action probably involves the inhibition of ISCs and claudin degradation and maintaining the stability of colon mucosa mechanical barrier.