Anti-inflammatory Efficacy of Combined Natural Alkaloid Berberine and S1PR Modulator Fingolimod at Low Doses in Ulcerative Colitis Preclinical Models.,Journal of Natural Products

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Anti-inflammatory Efficacy of Combined Natural Alkaloid Berberine and S1PR Modulator Fingolimod at Low Doses in Ulcerative Colitis Preclinical Models.
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-05-20 , DOI: 10.1021/acs.jnatprod.0c00175
Qian Han ₁ , Hua-Zheng Tang ₁ , Min Zou ₁ , Jie Zhao ₁ , Ling Wang ₂ , Zhao-Xiang Bian ₃ , Yan-Hong Li _{1,

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Affiliation

The natural alkaloid berberine is being studied as a drug candidate for the treatment of ulcerative colitis (UC). Fingolimod is an immunomodulator approved for the treatment of multiple sclerosis. Whether fingolimod use can be extended to UC and how it interacts with berberine remain unclear. In the present study, the anti-inflammatory efficacies of berberine, fingolimod, and a combination of half-doses of them was examined in mice with dextran sulfate sodium-induced colitis. In mice with subchronic colitis, 14-day oral administration of fingolimod had greater efficacy than berberine in ameliorating the disease clinical severity and colon shortening. However, in mice with chronic colitis, 30-day oral administration of berberine was more effective than fingolimod except on splenic swelling. Notably, the combination of half-doses of each drug was equally effective as the superior single drugs for two models and resulted in reduced splenic swelling in the chronic colitis model. The inhibition of cytokine expression and STAT3 activation, as well as binding to the sphingosine 1-phosphate receptor by both drugs, contributed to the combination efficacy. Our findings suggest that fingolimod in combination with berberine at reduced doses represents a novel therapy for UC that attains satisfactory efficacy with reduced potentials for adverse effects.

中文翻译：

联合天然生物碱小檗碱和 S1PR 调节剂芬戈莫德在溃疡性结肠炎临床前模型中的低剂量抗炎功效。

正在研究天然生物碱小檗碱作为治疗溃疡性结肠炎 (UC) 的候选药物。芬戈莫德是一种被批准用于治疗多发性硬化症的免疫调节剂。芬戈莫德的使用是否可以扩展到 UC 以及它如何与小檗碱相互作用尚不清楚。在本研究中，小檗碱、芬戈莫德及其半剂量组合的抗炎功效在葡聚糖硫酸钠诱导的结肠炎小鼠中进行了检查。在患有亚慢性结肠炎的小鼠中，14 天口服芬戈莫德在改善疾病临床严重程度和结肠缩短方面比小檗碱更有效。然而，在患有慢性结肠炎的小鼠中，除了脾肿胀外，口服小檗碱 30 天比芬戈莫德更有效。尤其，每种药物的半剂量组合与两种模型的优良单一药物同样有效，并导致慢性结肠炎模型中脾肿胀减少。两种药物对细胞因子表达和 STAT3 激活的抑制，以及与鞘氨醇 1-磷酸受体的结合，都有助于联合疗效。我们的研究结果表明，芬戈莫德与减少剂量的小檗碱联用代表了一种新的 UC 疗法，其获得令人满意的疗效并降低了不良反应的可能性。

更新日期：2020-06-26

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