Bai Yunpeng, Wang Guangwen, Lan Jinhua, Wu Ping, Liang Guowu, Huang Jinhui, Wu Zheng, Wang Yirong, Chen Chunbo
Center of Scientific Research, Maoming People's Hospital, Maoming 525000, China.
Department of Gastroenterology, Maoming People's Hospital, Maoming 525000, China.
Int J Anal Chem. 2022 Mar 21;2022:9293208. doi: 10.1155/2022/9293208. eCollection 2022.
Ulcerative colitis (UC) is a type of chronic idiopathic inflammatory bowel disease with a multifactorial pathogenesis and limited treatment options. The aim of the present study is to investigate the hydrogen deuterium exchange mass spectrometry (HDX-MS) behaviors of fermented deoxyanthocyanidins and their molecular mechanisms to alleviate UC by using quantum chemistry and network pharmacology.
Tandem MS indicated at least two fragmentation pathways through which deuterated vinylphenol-deoxyanthocyanidins could generate different product ions. Quantum calculations were conducted to determine the transition states of the relevant molecules and analyze their optimized configuration, vibrational characteristics, intrinsic reaction coordinates, and corresponding energies. The potential targets of deoxyanthocyanidins in UC were screened from a public database. The package was used for Gene Ontology (GO) and KEGG pathway analyses, and the protein-protein interactions (PPIs) of the targets were assessed using Search Tool for the Retrieval of Interacting Genes (STRING). Finally, molecular docking was implemented to analyze the binding energies and action modes of the target compounds through the online tool CB-Dock.
Quantum calculations indicated two potential fragmentation pathways involving the six-membered ring and dihydrogen cooperative transfer reactions of the vinylphenol-deoxyanthocyanidins. A total of 146 and 57 intersecting targets of natural and fermented deoxyanthocyanidins were separately screened out from the UC database and significant overlaps in GO terms and KEGG pathways were noted. Three shared hub targets (i.e., PTGS2, ESR1, and EGFR) were selected from the two PPI networks by STRING. Molecular docking results showed that all deoxyanthocyanidins have a good binding potential with the hub target proteins and that fermented deoxyanthocyanidins have lower binding energies and more stable conformations compared with natural ones.
Deoxyanthocyanidins may provide anti-inflammatory, antioxidative, and immune system regulatory effects to suppress UC progression. It is proposed for the first time that fermentation of deoxyanthocyanidins can help adjust the structure of the intestinal microbiota and increase the biological activity of the natural compounds against UC. Furthermore, HDX-MS is a helpful strategy to analyze deoxyanthocyanidin metabolites with unknown structures.
溃疡性结肠炎（UC）是一种慢性特发性炎症性肠病，发病机制多因素且治疗选择有限。本研究旨在利用量子化学和网络药理学研究发酵脱氧花青素的氢氘交换质谱（HDX-MS）行为及其缓解UC的分子机制。
串联质谱表明，氘代乙烯基苯酚-脱氧花青素可通过至少两种裂解途径产生不同的产物离子。进行量子计算以确定相关分子的过渡态，并分析其优化构型、振动特性、内禀反应坐标和相应能量。从公共数据库中筛选出脱氧花青素在UC中的潜在靶点。使用该软件包进行基因本体（GO）和KEGG通路分析，并使用相互作用基因检索工具（STRING）评估靶点的蛋白质-蛋白质相互作用（PPI）。最后，通过在线工具CB-Dock进行分子对接，分析目标化合物的结合能和作用模式。
量子计算表明，乙烯基苯酚-脱氧花青素存在涉及六元环和二氢协同转移反应的两种潜在裂解途径。分别从UC数据库中筛选出146个和57个天然和发酵脱氧花青素的交叉靶点，GO术语和KEGG通路存在显著重叠。STRING从两个PPI网络中选择了三个共享的枢纽靶点（即PTGS2、ESR1和EGFR）。分子对接结果表明，所有脱氧花青素与枢纽靶点蛋白均具有良好的结合潜力，且发酵脱氧花青素与天然脱氧花青素相比具有更低的结合能和更稳定的构象。
脱氧花青素可能具有抗炎、抗氧化和免疫系统调节作用，以抑制UC进展。首次提出，脱氧花青素发酵有助于调整肠道微生物群结构，并增加天然化合物对UC的生物活性。此外，HDX-MS是分析结构未知的脱氧花青素代谢产物的有用策略。
