Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin, 150040, People's Republic of China.
Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin, 150040, People's Republic of China.
J Pharm Biomed Anal. 2020 Jul 15;186:113277. doi: 10.1016/j.jpba.2020.113277. Epub 2020 Apr 3.
Psoriasis is a chronic, immune-mediated inflammatory skin disease and highly depends on inflammation and angiogenesis as well as other pathways. Our previous study showed that the withanolides from the leaves of Datura metel L. exhibited significant therapeutically effect on psoriasis, but the mechanisms concerning this effect have not been systematically studied. The purpose of this paper was to investigate the possible mechanism of withanolides for treating psoriasis using an integrated metabolomics and network pharmacology strategy. Untargeted metabolomics profiling of serum with UHPLC/Orbitrap MS and a multivariate data method were performed to discover the potential biomarkers and metabolic pathways. Afterward, the compound-target-pathway network of withanolides for psoriasis was constructed by virtue of network pharmacology. Finally, the crucial pathways were selected by integrating the results of metabolomics and network pharmacology, and then validated by ELISA and western blot analysis. The results showed that withanolides could exert excellent effects on psoriasis through regulating two types of pathways, angiogenesis and inflammation, including sphingolipids metabolism and HIF-1α/VEGF pathway, reflected by inhibiting the production of inflammatory cytokines (IL-1β, IL-6, IL-8, IFN-γ, TNF-α, HIF-1α and VEGF), as well as reducing the protein expressions of HIF-1α and VEGF. Our study successfully explained the polypharmcological mechanisms underlying the efficiency of withanolides from the D. metel L. leaves on treating psoriasis. Meanwhile, it was also valuable for performing a systematical investigation of herb medicines, as well as for efficiently predicting the therapeutic mechanisms of traditional Chinese medicine.
银屑病是一种慢性、免疫介导的炎症性皮肤病，高度依赖炎症和血管生成以及其他途径。我们之前的研究表明，曼陀罗叶中的醉茄内酯对银屑病具有显著的治疗作用，但这一作用的机制尚未得到系统研究。本文旨在采用整合代谢组学和网络药理学策略，研究醉茄内酯治疗银屑病的可能机制。采用 UHPLC/Orbitrap MS 和多变量数据分析方法对血清进行非靶向代谢组学分析，以发现潜在的生物标志物和代谢途径。之后，利用网络药理学构建醉茄内酯治疗银屑病的化合物-靶-途径网络。最后，通过整合代谢组学和网络药理学的结果，选择关键途径，并通过 ELISA 和 Western blot 分析进行验证。结果表明，醉茄内酯通过调节血管生成和炎症两种途径（包括鞘脂代谢和 HIF-1α/VEGF 途径），抑制炎症细胞因子（IL-1β、IL-6、IL-8、IFN-γ、TNF-α、HIF-1α 和 VEGF）的产生，降低 HIF-1α 和 VEGF 的蛋白表达，从而对银屑病发挥良好的治疗作用。本研究成功解释了曼陀罗叶醉茄内酯治疗银屑病的多药效机制。同时，这也为草药的系统研究以及中药治疗机制的有效预测提供了有价值的参考。
