Network Pharmacology Dissection of Multiscale Mechanisms for Jiaoqi Powder in Treating Ulcerative Colitis.
Network Pharmacology Dissection of Multiscale Mechanisms for Jiaoqi Powder in Treating Ulcerative Colitis.
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DOI：
10.1016/j.jep.2021.114109
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发表时间：
2021-04
影响因子：
5.4
通讯作者：
Shuting Wen;Zhuotai Zhong;Long He;Dike Zhao;Xu Chen;Hong Mi;Fengbin Liu
中科院分区：
文献类型：
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作者：
Shuting Wen;Zhuotai Zhong;Long He;Dike Zhao;Xu Chen;Hong Mi;Fengbin Liu
民族药理学相关性溃疡性结肠炎(UC)的发病率在全球范围内呈上升趋势，使其成为严重的公共卫生挑战。目前，还没有公认的治疗UC的方法。因此，探索UC治疗新的治疗策略具有重要的临床意义。交气散(JQP)是一种经典的中药方剂，常作为治疗消化道出血的补充和替代药物使用。因此JQP是治疗UC的一种潜在的替代药物。本研究的目的是探讨JQP对溃疡性结肠炎的保护作用，并用系统药理学的方法进一步探讨其作用机制。通过靶标捕捞、网络构建和富集分析，获得了JQP对UC的可能靶标和可能的作用机制。采用葡聚糖硫酸钠(DSS)诱导C57BL/6小鼠结肠炎的动物模型，进一步验证JQP的治疗作用机制。采用聚合酶链式反应、组织学染色、免疫组织化学、酶联免疫分析、流式细胞仪等方法，对JQP治疗UC的药理机制进行了研究。同样，还确定了2104个与UC相关的目标。PPI网络的构建导致了JQP的184个可能的治疗靶点的确定。在这184个核心目标中，有69个根据其DC值进行了进一步筛选。基因本体论(GO)、功能和京都基因和基因组百科全书(KEGG)途径分析表明，核心靶标主要集中在免疫反应和炎症信号通路上。随后的动物活体实验表明，健脾平通过显著降低弥漫性结肠炎大鼠诱导高水平表达核因子-κB/p65、IL-1β、IL-6和肿瘤坏死因子-α的能力，改善结肠炎的症状和组织学改变。JQP还能降低DSS小鼠COX-2、CCL2、CXCL2、HIF-1α、MMP3、MMP9水平，调节Th17/Treg细胞平衡。结论JQP可通过改善黏膜炎症反应、修复肠屏障、调节Th17/Treg免疫平衡来治疗UC。本研究结果为UC的治疗提供了新的见解，并进一步阐明了中药药物开发的理论和实践意义。
Ethnopharmacological relevanceThe incidence of ulcerative colitis (UC) is increasing worldwide, making it a serious public health challenge. Currently, there are no accepted curative treatments for UC. As such, the exploration of new therapeutic strategies for UC treatment is of considerable clinical importance. Jiaoqi powder (JQP) is a classic Chinese medicinal formula commonly used as a complementary and alternative medicine for treating gastrointestinal bleeding. JQP is thus a potential alternative medicine for UC treatment. However, the protective mechanism underlying the action of JQP has not been elucidated, thereby, necessitating further studies to decipher the mechanisms involved in the complex interplay among its components.Aim of the studyTo explore the protective effect of JQP against UC and to further investigate its mechanismin silicoandin vivousing a systems pharmacology approach.Materials and methodsA systems pharmacology approach was used to predict the active components of JQP. Putative targets and the potential mechanism of JQP on UC were obtained through target fishing, network construction, and enrichment analyses. An animal-based model of dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice was further used to validate the treatment mechanisms of JQP. The underlying pharmacological mechanisms of JQP in UC were determined using polymerase chain reaction tests, histological staining, immunohistochemistry, enzyme-linked immunoassays, and flow cytometry analysis.ResultsIn this study, 17 effective components and 941 potential targets of JQP were identified. Similarly, 2104 UC-related targets were also identified. Construction of PPI networks led to the identification of 184 putative therapeutic targets of JQP. Sixty-nine core targets among these 184 were further screened based on their DC values. Gene ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the core targets were primarily enriched in immune response and inflammatory signalling pathways. Subsequent animal-basedin vivoexperiments revealed that JQP ameliorated symptoms and histological changes in DSS colitis by significantly impairing DSS's ability to induce high expression levels of NF-κB/p65, IL-1β, IL-6, and TNF-α. JQP also reduced the levels of COX-2, CCL2, CXCL2, HIF-1α, MMP3 and MMP9 and regulated the Th17/Treg cell balance in DSS-induced mice.ConclusionsThis study demonstrated that JQP could treat UC by improving the mucosal inflammatory response, repairing the intestinal barrier, and modulating the Th17/Treg immune balance. The results of this study provide new insights into UC treatment and further elucidate the theoretical and practical implications of the pharmaceutical development of TCMs.