Department of Neurosurgery, Wan Fang Hospital, Taipei Medical University, Taipei, ROC, Taiwan.
Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei, ROC, Taiwan.
Sci Rep. 2018 Oct 8;8(1):14927. doi: 10.1038/s41598-018-33204-5.
The incidence of inflammatory bowel disease (IBD) has markedly increased. Our research findings during the past showed that medicinal plant extracts and the derived phytochemical components from Wedelia chinensis (WC) can have strong anti-colitis activities. Here, we further identified the key component phytochemicals from active fractions of different WC preparations (WCHA) that are responsible for the protective effect of WCHA in colitis mice. Of the 3 major compounds (wedelolactone, luteolin and apigenin) in this fraction, luteolin had the highest anti-inflammatory effect in vivo. Using a next-generation sequencing (NGS) (e.g., RNA-seq) system to analyze the transcriptome of colorectal cells/tissues in mice with dextran sulfate sodium (DSS)-induced colitis with/without phytochemicals treatment, luteolin was found to strongly suppress the DSS-activated IL-17 pathway in colon tissue. In addition, co-treatment with wedelolactone and luteolin had a synergistic effect on the expression level of some IL-17 pathway-related genes. Interestingly, our NGS analyses also indicated that luteolin and wedelolactone can specifically suppress the expression of NLRP3 and NLRP1. Using a 3-dimensional cell co-culture system, we further demonstrated that luteolin could efficiently suppress NLRP3 expression via disruption of IL-17A signaling in inflamed colon tissue, which also indicates the pharmacological potential of luteolin and wedelolactone in treating IBD.
炎症性肠病（IBD）的发病率显著增加。我们过去的研究结果表明，药用植物提取物和鸭跖草（WC）衍生的植物化学成分具有很强的抗结肠炎活性。在这里，我们进一步鉴定了不同 WC 制剂（WCHA）活性部分中负责 WCHA 在结肠炎小鼠中保护作用的关键成分植物化学物质。在该部分的 3 种主要化合物（wedelolactone、木犀草素和芹菜素）中，木犀草素在体内具有最高的抗炎作用。使用下一代测序（NGS）（例如，RNA-seq）系统分析葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠结直肠细胞/组织的转录组，发现木犀草素可强烈抑制结肠组织中 DSS 激活的 IL-17 途径。此外，wedelolactone 和木犀草素的共同处理对一些与 IL-17 途径相关的基因的表达水平具有协同作用。有趣的是，我们的 NGS 分析还表明，木犀草素和 wedelolactone 可以特异性抑制 NLRP3 和 NLRP1 的表达。使用三维细胞共培养系统，我们进一步证明木犀草素可以通过破坏炎症结肠组织中的 IL-17A 信号来有效抑制 NLRP3 的表达，这也表明木犀草素和 wedelolactone 在治疗 IBD 方面的药理学潜力。
