2014年药物研发最热门靶点证实，TGFβ/Smad信号通路已成为治疗溃疡性结肠炎(UC)的关键靶点，并且NF-κB通过对炎性介质的调控在UC炎症反应中起着关键作用。最新研究报道，穿心莲提取物HMPL-004成功获得美国FDA批准用于治疗UC的III期临床试验。本课题组以中药有效成分穿心莲内酯为母核进行结构修饰，合成并筛选出具有明显抗炎作用的穿心莲内酯-α-硫辛酸耦合物(AL-1)。前期研究证实AL-1对UC具有明显的治疗作用；进一步机制研究显示，AL-1可显著抑制p65和IκBα的磷酸化水平。但是，关于AL-1如何调控TGFβ1/Smad和NF-κB信号通路治疗UC的具体机制及NF-κB具体作用位点的研究尚未完全阐明。因此，本课题以TGFβ1/Smad和NF-κB信号通路为切入点，从分子、细胞和整体动物水平，进一步揭示AL-1改善UC的分子作用机理，为UC的有效防治提供科学依据。

In 2014, the most popular targets for drug development had confirmed that TGFβ/Smad signaling pathway had become the key target for treatment of ulcerative colitis (UC), and NF-κB played an important role in the inflammation of UC. Andrographis extract HMPL-004 successfully obtained approval from the FDA of USA, which could be used for the Phase III clinical trials of UC. Therefore, on the basis of andrographolide (the active ingredient of andrographis), we synthesized and screened andrographolide-α-lipoic acid conjugates (AL-1) which had a significant role in the treatment of UC. Our results showed AL-1 could significantly inhibit the phosphorylation of p65 and IκBα. However, it has not been fully elucidated how TGFβ1/Smad and NF-κB signaling pathway is regulated in the treatment of UC. Therefore, according to the TGFβ1/Smad and NF-κB signaling pathway, we’ll reveal the molecular mechanism of AL-1 on treatment of UC from the molecular, cellular and animal level, and it will provide more adequate scientific evidences for the treatment of UC.