Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China.
No.30 Middle School of Taiyuan, Taiyuan, 030002, China.
Eur J Pharmacol. 2019 Jul 5;854:9-21. doi: 10.1016/j.ejphar.2019.03.059. Epub 2019 Apr 3.
Colitis-associated cancer (CAC) has a close relationship with ulcerative colitis (UC). Therapeutic effect of Schisandrin B (SchB) on UC and CAC remains largely unknown. We investigated the preventative effect of SchB on the dextran sulphate sodium (DSS) model of UC and azoxymethane (AOM)/DSS model of CAC. Furthermore, focal adhesion kinase (FAK) activation and influence on commensal microbiota are important for UC treatment. Impact on FAK activation by SchB in UC development was evaluated in vivo and vitro. We also conducted 16S rRNA sequencing to detect regulation of gut microbiota by SchB. Enhanced protection of intestinal epithelial barrier by SchB through activating FAK contributed to protective effect on colon for the fact that protection of SchB can be reversed by inhibition of FAK phosphorylation. Furthermore, influence on gut microbiota by SchB also played a significant role in UC prevention. Our results revealed that SchB was potent to prevent UC by enhancing protection of intestinal epithelial barrier and influence on gut microbiota, which led to inhibition of CAC. SchB was potential to become a new treatment for UC and prevention of CAC.
结肠炎相关癌症(CAC)与溃疡性结肠炎(UC)密切相关。五味子乙素(SchB)对 UC 和 CAC 的治疗效果在很大程度上尚不清楚。我们研究了 SchB 对葡聚糖硫酸钠(DSS)诱导的 UC 模型和氧化偶氮甲烷(AOM)/DSS 诱导的 CAC 模型的预防作用。此外,黏着斑激酶(FAK)的激活及其对共生微生物群的影响对于 UC 的治疗很重要。在体内和体外评估了 SchB 对 UC 发展中 FAK 激活的影响。我们还进行了 16S rRNA 测序,以检测 SchB 对肠道微生物群的调节。SchB 通过激活 FAK增强了肠道上皮屏障的保护作用,从而对结肠起到了保护作用,因为 FAK 磷酸化的抑制可以逆转 SchB 的保护作用。此外,SchB 对肠道微生物群的影响在 UC 的预防中也起着重要作用。我们的结果表明,SchB 通过增强肠道上皮屏障的保护作用和对肠道微生物群的影响,从而抑制 CAC,对 UC 具有很强的预防作用。SchB 有可能成为 UC 治疗和 CAC 预防的一种新方法。