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Abstract：
To investigate the therapeutic effects of phellodendrine in ulcerative colitis (UC) through the AMPK/mTOR pathway. Volunteers were recruited to observe the therapeutic effects of Compound Cortex Phellodendri Liquid (Huangbai liniment). The main components of Compound Cortex Phellodendri Liquid were analysed via network pharmacology. The target of phellodendrine was further analysed. Caco-2 cells were cultured, and H2 O2 was used to stimulate in vitro cell model. Expression levels of LC3, AMPK, p-AMPK, mTOR and p-mTOR were detected via Western blotting and through immunofluorescence experiments. The therapeutic effects of phellodendrine were analysed via expression spectrum chip sequencing. The sequencing of intestinal flora further elucidated the therapeutic effects of phellodendrine. Compared with the control group, Compound Cortex Phellodendri Liquid could substantially improve the healing of intestinal mucosa. Network pharmacology analysis revealed that phellodendrine is the main component of Compound Cortex Phellodendri Liquid. Moreover, this alkaloid targets the AMPK signalling pathway. Results of animal experiments showed that phellodendrine could reduce the intestinal damage of UC compared with the model group. Findings of cell experiments indicated that phellodendrine treatment could activate the p-AMPK /mTOR signalling pathway, as well as autophagy. Expression spectrum chip sequencing showed that treatment with phellodendrine could promote mucosal healing and reduce inflammatory responses. Results of intestinal flora detection demonstrated that treatment with phellodendrine could increase the abundance of flora and the content of beneficial bacteria. Phellodendrine may promote autophagy by regulating the AMPK-mTOR signalling pathway, thereby reducing intestinal injury due to UC.
摘要：
探讨黄柏碱通过AMPK/mTOR通路对溃疡性结肠炎(UC)的治疗作用。招募志愿者观察复方黄柏液（黄柏擦剂）的治疗效果。采用网络药理学方法对复方黄柏液的主要成分进行分析。进一步分析黄柏碱的靶标。培养Caco-2细胞，用H2O2刺激体外细胞模型。LC3、AMPK、p-AMPK,通过蛋白质印迹和免疫荧光实验检测mTOR和p-mTOR。通过表达谱芯片测序分析黄柏碱的治疗效果。肠道菌群的测序进一步阐明了黄柏碱的治疗作用。与对照组相比,复方黄柏液能显著改善肠黏膜愈合。网络药理学分析表明黄柏碱是复方黄柏液的主要成分。此外，这种生物碱靶向AMPK信号通路。动物实验结果表明黄柏碱与模型组比较,可减轻UC的肠道损伤。细胞实验结果表明黄柏碱处理可以激活p-AMPK/mTOR信号通路,以及自噬。表达谱芯片测序显示黄柏碱可促进粘膜愈合，减轻炎症反应。肠道菌群检测结果表明，黄柏碱治疗可增加菌群丰度和有益菌含量。黄柏碱可能通过调节AMPK-mTOR信号通路促进自噬,从而减少由于UC引起的肠损伤。
