Liu Wenjuan, Zhang Xiaoying, Ma Tiancheng, Wang Jinyu, Lv Xinyan, Wu Bo, Yan Tingxu, Jia Ying
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China.
School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, China.
J Ethnopharmacol. 2022 Jul 15;293:115282. doi: 10.1016/j.jep.2022.115282. Epub 2022 Apr 9.
The prescription of Wei-Tong-Xin (WTX) is improved based on the prescription "Wanyingyuan", a famous decoction documented in the book of Huatuozhongzangjing in the Han dynasty. Many years of clinical verification have demonstrated that WTX can be used to treat gastrointestinal diseases, especially gastric ulcer (GU). However, the potential pharmacological mechanism is undefined.
This research was conducted to explore the pharmacological mechanisms under the consideration of the therapeutical effect of WTX against GU by combining the network pharmacology strategy and in-vivo verified experiments.
A prediction network describing the relationship between WTX and GU was established based on information collected from multiple databases. Then, the intersecting protein-protein interaction (PPI) network of the drug-disease overlapping gene targets was constructed, and several key targets related to both WTX and GU were obtained. Besides, the Gene Ontology (GO) biological enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the key target genes and pathways of WTX against GU. Then, the candidate targets and signaling pathways of network pharmacology were validated in a rat model of GU induced by indomethacin following the results and available proof.
There are 243 targets obtained from the 65 active ingredients in WTX, and 1362 disease targets related to GU were identified. Then, 6 key targets were determined with the PPI interaction network, which was structured from 126 overlapping gene targets. GO and KEGG analyses revealed that the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signaling pathway might play a crucial role in the therapeutic mechanism of GU. In vivo verified experiments, WTX significantly reduced the ulcer area and improved the histopathological appearance of gastric tissues. Moreover, down-regulated the protein levels of IL6, TNF-α, and Caspase 3 in the gastric tissues while up-regulating the expression of p-PI3K, p-AKT, p-P53, and VEGFA compared to the model group.
WTX, an ancient traditional Chinese medicine (TCM) compound prescription, may affect the inflammatory response and apoptosis process by regulating PI3K/AKT signaling pathway and related gene targets. Therefore, it is an effective drug candidate for the modern treatment of GU.
胃通欣（WTX）方剂是在汉代《华陀中藏经》记载的著名方剂“万应元”基础上改良而来。多年临床验证表明，WTX可用于治疗胃肠道疾病，尤其是胃溃疡（GU）。然而，其潜在的药理机制尚不明确。
本研究旨在结合网络药理学策略和体内验证实验，探讨WTX治疗GU的疗效背后的药理机制。
基于从多个数据库收集的信息，建立了一个描述WTX与GU之间关系的预测网络。然后，构建了药物 - 疾病重叠基因靶点的交叉蛋白质 - 蛋白质相互作用（PPI）网络，获得了几个与WTX和GU均相关的关键靶点。此外，进行了基因本体（GO）生物富集分析和京都基因与基因组百科全书（KEGG）通路分析，以研究WTX治疗GU的关键靶基因和通路。然后，根据结果和现有证据，在吲哚美辛诱导的GU大鼠模型中验证网络药理学的候选靶点和信号通路。
从WTX的65种活性成分中获得了243个靶点，并鉴定出1362个与GU相关的疾病靶点。然后，通过由126个重叠基因靶点构建的PPI相互作用网络确定了6个关键靶点。GO和KEGG分析表明，磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/AKT）信号通路可能在GU的治疗机制中起关键作用。在体内验证实验中，WTX显著减小了溃疡面积，改善了胃组织的组织病理学外观。此外，与模型组相比，WTX下调了胃组织中IL6、TNF-α和Caspase 3的蛋白水平，同时上调了p-PI3K、p-AKT、p-P53和VEGFA的表达。
WTX作为一种古老的中药复方制剂，可能通过调节PI3K/AKT信号通路及相关基因靶点来影响炎症反应和细胞凋亡过程。因此，它是现代治疗GU的有效候选药物。
