Abstract：
This study compared the therapeutic difference effects of the raw and scorched rhubarb for the treatment of ulcerative colitis(UC) and explored their difference in chemical components and mechanisms by using ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-QE-Orbitrap-MS) and network pharmacology. The UC therapeutic effects of Shaoyao Decoction with the raw rhubarb or the scorched rhubarb were evaluated by dextran sulfate sodium(DSS)-induced mouse model. The results showed that Shaoyao Decoction with either the raw rhubarb or the scorched rhubarb could relieve the UC symptoms of mice to different extents, while the scorched rhubarb-based formula showed advantages in reducing hemorrhagic diarrhea and inflammation levels. UPLC-QE-Orbitrap-MS was used to identify a total of 78 small molecules in the water decoction of the raw and scorched rhubarb. Multivariate statistical methods were used to screen components increasing significantly after the scorching process. The seven compounds included five free anthraquinones, gallic acid, and 5-hydroxymethylfurfural(HMF). Meanwhile, the nine compounds decreasing scorching were mainly combined anthraquinones and catechins-related compounds. Network pharmacology and molecular docking suggested that free anthraquinones, gallic acid, and 5-HMF may act on core targets such as B-cell lymphoma-2(BCL2), epidermal growth factor receptor(EGFR), tumor necrosis factor(TNF), and caspase-3(CASP3) and influence the signaling pathways such as phosphoinositide-3-kinase/protein kinase B(PI3K/Akt), hypoxia inducible factor-1(HIF-1), TNF, and mitogen-activated protein kinase(MAPK), so as to regulate the inflammation response, oxidative stress, and cell apoptosis to relieve UC symptoms. This study compared the therapeutic effects and chemical components of the raw and scorched rhubarb, providing the clinical reference for using rhubarb to treat UC.
摘要：
本研究采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱(UPLC-QE-Orbitrap-MS)和网络药理学方法,比较生大黄和烤焦大黄治疗溃疡性结肠炎(UC)的疗效差异,并探讨其化学成分差异及机制。通过葡聚糖硫酸钠（DSS）诱导的小鼠模型评价芍药汤与生大黄或烧焦大黄的UC治疗效果。结果表明，芍药汤加生大黄或烧焦大黄均能不同程度地缓解小鼠UC症状，而以烤焦大黄为基础的配方在降低出血性腹泻和炎症水平方面显示出优势。UPLC-QE-Orbitrap-MS用于鉴定生大黄和烧焦大黄的水汤剂中总共78个小分子。采用多变量统计方法筛选焦烧过程后显著增加的成分。这7种化合物包括5种游离蒽醌,没食子酸,和5-羟甲基糠醛(HMF)。同时,减少灼热的9个化合物主要是蒽醌和儿茶素相关化合物。网络药理学和分子对接表明，游离蒽醌，没食子酸,5-HMF可能作用于B细胞淋巴瘤-2（BCL2）等核心靶标，表皮生长因子受体（EGFR），肿瘤坏死因子(TNF),和caspase-3（CASP3），并影响信号通路，如磷酸肌醇-3-激酶/蛋白激酶B（PI3K/Akt），缺氧诱导因子-1(HIF-1),TNF,和丝裂原活化蛋白激酶（MAPK），从而调节炎症反应，氧化应激，细胞凋亡减轻UC症状。本研究比较了生大黄和烧焦大黄的治疗效果和化学成分，为大黄治疗UC提供临床参考。
