玫瑰果对溃疡性结肠炎的影响:基于网络药理学和实验验证的综合分析
Effects of Rosa roxburghii Tratt on Ulcerative Colitis: An Integrated Analysis of Network Pharmacology and Experimental Validation.
发表日期:2023 Aug 02
作者:
Yu-Hong Kang, Ting Zhou, Shou-Xun Wu, Xing-Jie Li, Xiao-Yi Huang, Rui Xia, Yi-Han Ling, He-Ting Zhou, Shu-Wen Zhang, Wen-Ya Yin
来源:
PHARMACOLOGY & THERAPEUTICS
摘要:
罗茨维奇蔷薇是一种传统的中国植物,被用来治疗不同的炎症性疾病。本研究的目的是利用网络药理学和实验证实,研究罗茨维奇蔷薇提取物(RRTE)对溃疡性结肠炎(UC)的作用机制。使用高效液相色谱-四极杆/轨道阱质谱的方法,在从果实中提取活性成分后,快速识别出RRTE中所含的物质。接着,将网络药理学与分子对接相结合,以RRTE中的活性成分为研究对象,探索RRTE对UC的关键靶点和潜在机制。数据以可视化方式呈现。最后,利用DSS诱导的NCM460 UC模型,进一步验证了RRTE在缓解UC中的药理效应。结果显示,鉴定出了RRTE中的25个成分。收集了与RRTE活性成分有关的250个靶点和与UC相关的5376个靶点。此外,蛋白质相互作用(PPI)网络的系统分析表明,表皮生长因子受体(EGFR)、磷酸肌醇-3-激酶调节亚单位1(PIK3R1)和丝氨酸/苏氨酸激酶1(AKT1)是RRTE在治疗UC中的关键靶点。综合调控网络分析显示,RRTE通过EGFR介导的PI3K/Akt通路减轻UC,并且分子对接显示,活性成分能够强烈结合EGFR、PIK3R1和AKT1。此外,RRTE在体外明显减轻了DSS诱导的NCM460细胞损伤,并且显著降低了EGFR、PIK3R1和p-AKT的蛋白表达水平。此外,RRTE显著调节了与凋亡相关的蛋白Apoptotic protease-activating factor 1(Apaf1)、剪切的caspase-3、B细胞淋巴瘤-2(Bcl2)和Bcl2 associated X protein(Bax)的表达。总之,RRTE的成分复杂,通过EGFR介导的PI3K/Akt通路可以缓解UC。
Rosa roxburghii Tratt is a traditional Chinese plant that has been used to treat different inflammatory diseases. The purpose of this study was to investigate the mechanism of action of Rosa roxburghii Tratt extract (RRTE) against ulcerative colitis (UC) using network pharmacology and experimental validation. HPLC-Q/Orbitrap MS was used to rapidly identify the substances contained in RRTE after extracting the active components from the fruit. Then, network pharmacology combined with molecular docking was used to explore the critical target and potential mechanism of RRTE against UC using the active ingredients in RRTE as the research object. Data are presented in a visual manner. Finally, the pharmacological effects of RRTE in alleviating UC were further verified using a DSS-induced UC model of NCM460. The results showed that 25 components in RRTE were identified. A total of 250 targets of the active components and 5376 targets associated with UC were collected. Furthermore, a systematic analysis of the Protein-Protein Interaction (PPI) networks suggests that epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and serine/threonine kinase 1 (AKT1) are critical targets for RRTE in the treatment of UC. A comprehensive regulatory network analysis showed that RRTE alleviated UC through the EGFR-mediated PI3K/Akt pathway, and molecular docking showed that active components could strongly bind to EGFR, PIK3R1, and AKT1. In addition, RRTE alleviated dextran sulfate sodium salt (DSS)-induced cell injury and significantly decreased the protein expression levels of EGFR, PIK3R1, and p-AKT in NCM460 cells in vitro. Furthermore, RRTE significantly regulated the expression of the apoptosis-related proteins Apoptotic protease-activating factor 1 (Apaf1), cleaved caspase-3, B-cell lymphoma-2 (Bcl2), and Bcl2 associated X protein (Bax). In conclusion, the components of RRTE are complex, and RRTE can relieve UC through the EGFR-mediated PI3K/Akt pathway.