Wang Hai-Yan, Zhao Hai-Mei, Wang Yao, Liu Yi, Lu Xiu-Yun, Liu Xue-Ke, Chen Fang, Ge Wei, Zuo Zheng-Yun, Liu Duan-Yong
Party and School Office, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
School of Basic Medical Sciences, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
Front Pharmacol. 2019 Mar 6;10:170. doi: 10.3389/fphar.2019.00170. eCollection 2019.
The nuclear factor (NF)-κB signaling pathway plays an important role in the initialization and development phase of inflammatory injuries, including inflammatory bowel disease (IBD). Sishen Wan (SSW) is a classic Chinese patent medicine listed in the Chinese Pharmacopoeia, which is usually used to treat chronic colitis; however, it is unclear whether SSW can treat IBD the NF-κB signaling pathway. In the present study, the therapeutic effect of SSW was demonstrated by the decreased index of colonic weight, macroscopic and microscopic score, and pathological observation in chronic colitis induced by trinitrobenzene sulfonic acid. In colonic mucosa of rats with chronic colitis, SSW reduced the levels of calprotectin and eliminated oxidative lesions; downregulated expression of interferon-γ, interleukin (IL)-1β and IL-17; increased expression of IL-4; and suppressed expression of NF-κB p65, and NF-κB essential modulator (NEMO)-like kinase (NLK). Furthermore, SSW inhibited ubiquitinated NEMO, ubiquitin-activated enzyme, and E2i activation, and phosphorylation of downstream proteins (cylindromatosis protein, transforming growth factor-β-activated kinase and P38). These results show that the therapeutic effects of SSW in chronic colitis were mediated by inhibiting the NEMO/NLK signaling pathway to suppress NF-κB activation.
核因子（NF）-κB信号通路在包括炎症性肠病（IBD）在内的炎症性损伤的起始和发展阶段发挥着重要作用。四神丸（SSW）是《中国药典》中收录的一种经典中成药，常用于治疗慢性结肠炎；然而，尚不清楚SSW是否能通过NF-κB信号通路治疗IBD。在本研究中，通过三硝基苯磺酸诱导的慢性结肠炎模型中结肠重量指数、大体和显微镜评分的降低以及病理观察，证实了SSW的治疗效果。在慢性结肠炎大鼠的结肠黏膜中，SSW降低了钙卫蛋白水平并消除了氧化损伤；下调了干扰素-γ、白细胞介素（IL）-1β和IL-17的表达；增加了IL-4的表达；并抑制了NF-κB p65和NF-κB必需调节因子（NEMO）样激酶（NLK）的表达。此外，SSW抑制了泛素化的NEMO、泛素激活酶和E2i的激活以及下游蛋白（圆柱瘤蛋白、转化生长因子-β激活激酶和P38）的磷酸化。这些结果表明，SSW在慢性结肠炎中的治疗作用是通过抑制NEMO/NLK信号通路来抑制NF-κB激活介导的。
