Hebei Key Laboratory of Specialty Animal Germplasm Resources Exploration and Innovation (Under Planning), College of Animal Science and Technology, Hebei Normal University of Science & Technology, Qinhuangdao, 066004, China.
Shijiazhuang Zhongnongtongchuang (ZNTC) Biotechnology Co., Ltd., Shijiazhuang, 052463, China.
J Physiol Biochem. 2021 May;77(2):283-294. doi: 10.1007/s13105-021-00796-y. Epub 2021 Feb 17.
The ulcerative colitis (UC) is a typical inflammatory bowel disease (IBD) causing great damages, while strictosamide (STR) is a natural alkaloid that possesses strong anti-inflammatory property in infection and inflammation-related diseases. Our study is aimed at evaluating the anti-inflammatory activity of STR in the course of UC. Briefly, male Balb/c mice were treated with 3.5% dextran sulfate sodium (DSS) for 6 consecutive days to establish an acute model of UC, and the administration of gradient concentrations of STR was subsequently performed. Accordingly, colonic pathological alterations including the reduced ratio of colon weight/length, decreased disease activity index (DAI), and attenuated H&E damage were found in UC mice after STR treatment. Based on the analyses of real-time PCR and western blot, downregulation of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) was also determined in the colonic tissue of UC mice after the treatment of STR. ELISA and immunohistochemical staining further suggest the relief of inflammation in UC mice with decreased expressions of MPO and iNOS after STR treatment. In addition, STR was also validated to significantly inhibit NF-κB signaling in UC mice by western blot and Electrophoretic Mobility Shift Assay (EMSA). Meanwhile, restricted inflammation was also determined in STR-treated IEC6 and HT-29 cells. The utilization of PDTC, an inhibitor of NF-κB, further demonstrated that STR ameliorated the inflammation by inhibiting the NF-κB signaling in vitro. In summary, our study suggests that STR could be a potential candidate for IBD therapy.
溃疡性结肠炎(UC)是一种典型的炎症性肠病(IBD),会造成严重损害,而斯图诺醇(STR)是一种天然生物碱,在感染和炎症相关疾病中具有很强的抗炎特性。我们的研究旨在评估 STR 在 UC 病程中的抗炎活性。简而言之,雄性 Balb/c 小鼠用 3.5%葡聚糖硫酸钠(DSS)连续处理 6 天,以建立急性 UC 模型,随后给予梯度浓度的 STR 进行处理。因此,在 STR 处理后,UC 小鼠的结肠组织中观察到结肠病理改变,包括结肠重量/长度比降低、疾病活动指数(DAI)降低和 H&E 损伤减轻。基于实时 PCR 和 Western blot 分析,在 STR 处理后的 UC 小鼠结肠组织中还发现促炎细胞因子(TNF-α、IL-1β和 IL-6)下调。ELISA 和免疫组织化学染色进一步表明,STR 处理后 UC 小鼠的 MPO 和 iNOS 表达减少,炎症得到缓解。此外,Western blot 和电泳迁移率变动分析(EMSA)还表明 STR 可显著抑制 UC 小鼠的 NF-κB 信号。同时,STR 处理的 IEC6 和 HT-29 细胞也显示出炎症受限。NF-κB 抑制剂 PDTC 的利用进一步证明 STR 通过抑制 NF-κB 信号转导在体外改善了炎症。总之,我们的研究表明 STR 可能是治疗 IBD 的潜在候选药物。