基于肠道菌群和NF-кB信号通路调控的维药薰鲁香治疗溃疡性结肠炎药效物质基础及作用机制研究

溃疡性结肠炎(UC)是一种慢性非特异性炎性肠病，临床上缺乏有效治疗药物。改善肠道菌群失调及其引起的肠道炎症是治疗UC的重要策略。维药薰鲁香临床治疗UC效果显著且副作用小，然而其抗UC药效物质基础及作用机制尚不明确。课题组前期研究发现薰鲁香富含萜类成分，其甲醇提物可改善葡聚糖硫酸钠（DSS）介导UC小鼠疾病活动指数及结肠组织病理学变化，抑制LPS活化RAW264.7细胞中NF-кB的异常激活；且文献研究表明薰鲁香具有调节肠道菌群的潜力。因此本课题拟利用DSS介导UC小鼠模型进行活性追踪，采用多种色谱和光谱技术探明药效部位化学成分；通过分子生物学和肠道菌群基因组测序技术，在动物和细胞水平研究主要活性成分对肠道菌群失调及NF-кB信号通路关键蛋白表达的影响。本项目的开展将阐明薰鲁香治疗UC的药效物质基础及其作用机制，同时也可为抗UC新型药物的研发提供有价值的模板结构。

Ulcerative colitis (UC) is a serious chronic inflammatory bowl disease. However, up to date, there are absent effective drugs for the treatment of UC in clinic. Ameliorating gut microbiota dysbiosis and inflammation are considered efficient strategies in UC treatment. Uygur medicine mastich has been clinically used to treat UC in Xinjiang area with less side effects. However, the material basis and the underlying mechanism of mastich against UC are not clear yet, which seriously hinder the development and usage of it beyond Xinjiang area. Our preliminary study revealed that mastich was abundant in terpenoids, and the crude extract of mastich could improve disease active index and colonic pathological changes in DSS-induced UC mice. In addition, crude extract of mastich was found capable of inhibiting abnormal activation of NF-кB in LPS-activated RAW 264.7 cell. Furthermore, published data suggested that mastich possessed prebiotic potential. Therefore, in the current study, based on DSS-induced UC mice model, we initiate bioassay-guided investigation on bioactive constituents from mastich with anti-UC potential..Multiple chromatographic and spectral method will be used to isolate and identify pure compounds from the effective fractions of mastic extract. The impacts of major bioactive constituents on the gut microbiota and NF-кB signaling pathway will be determined with cell culture system and UC mice by using molecular biological and 16s rRNA geneome sequencing technologies. The current study will advance scientific knowledge of material basis of mastich and its potential mechanism of action in UC treatment, and promote the discovery of leading compounds for UC treatment from natural source.