Ethnopharmacological relevance

Lagotis integra W. W. Smith (L. integra W. W. Smith) is an important origin plant of the famous Tibetan medicine HERBA LAGOTIS. It was documented to treat “Chi Ba” disease clinically, the symptoms of which are similar to ulcerative colitis (UC).

Aims of this study

To screen out the active components and study the mechanisms of L. integra W. W. Smith treating UC.

Materials and methods

The components of L. integra W. W. Smith were comprehensively analyzed using UHPLC-Q-TOF/MS method. The mechanisms were investigated using network pharmacology method including target prediction, protein-protein interaction network analysis and gene enrichment analysis. Then, the mechanisms were verified using Dextran Sulfate Sodium (DSS)-induced UC model. Finally, the core active components were further screened out through molecular docking.

Results

The results showed that 32 major components were identified including 8 flavonoids, 9 phenylpropanoid glycosides, 13 iridoid glycosides and 1 phenolic acid. 76 potential core therapeutic targets and top 5 key targets, which were AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor (VEGFA), tumor necrosis factor-α (TNF-α), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), were screened out according to network pharmacology analysis. Animal experiments confirmed that those compounds could downregulate the expression levels of the 5 key target proteins in colonic tissue of mice to exert excellent anti-UC effect. Molecular docking results showed that the main active components were echinacoside, hemiphroside B, plantamajoside, plantainoside D, 10-O-trans-isoferuloyl catalpol and scutellarioside II.

Conclusions

For the first time, our study provides insights into the effective materials and molecular mechanisms of L. integra W. W. Smith treating UC, which contributes to the understanding of its pharmacodynamics.

中文翻译：

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基于网络药理学、分子对接和实验验证的藏药Lagotis integra WW Smith治疗DSS诱导的溃疡性结肠炎的有效材料和机制研究

民族药理学相关性

西洋参( L. integra W. W. Smith)是著名藏药药草的重要原产植物。据记载，临床上可治疗“赤巴”病，其症状与溃疡性结肠炎（UC）相似。

本研究的目的

筛选活性成分并研究L. integra WW Smith治疗UC的作用机制。

材料和方法

使用 UHPLC-Q-TOF/MS 方法对L. integra WW Smith的成分进行了全面分析。采用网络药理学方法研究其机制，包括靶点预测、蛋白质-蛋白质相互作用网络分析和基因富集分析。然后，使用葡聚糖硫酸钠（DSS）诱导的UC模型验证了这些机制。最后通过分子对接进一步筛选出核心活性成分。

结果

结果表明，共鉴定出32个主要成分，其中黄酮类8个，苯丙烷苷9个，环烯醚萜苷13个，酚酸1个。76个潜在核心治疗靶点和前5个关键靶点，分别是AKT丝氨酸/苏氨酸激酶1（AKT1）、血管内皮生长因子（VEGFA）、肿瘤坏死因子-α（TNF-α）、表皮生长因子受体（EGFR）和根据网络药理学分析筛选出caspase-3（CASP3）。动物实验证实，这些化合物可以下调小鼠结肠组织中5个关键靶蛋白的表达水平，发挥优异的抗UC作用。分子对接结果表明，主要活性成分为松果菊苷、半红花苷B、植物苦参苷、车前草苷D、10-O-反式-异阿魏酰梓醇和黄芩苷 II。

结论

我们的研究首次提供了对L. integra WW Smith 治疗 UC 的有效材料和分子机制的见解，这有助于理解其药效学。