Zhou Ming
Nanjing University of Chinese Medicine, School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing 210023, China.
Evid Based Complement Alternat Med. 2022 Jun 17;2022:7536042. doi: 10.1155/2022/7536042. eCollection 2022.
Although modified Liu Jun Zi decoction (MLD) has favorable outcomes for chronic atrophic gastritis (CAG) in clinics, the identification of its active ingredients and the molecular mechanism of pharmacology are still unknown and need to be solved urgently. In the study, we screened 170 active components of MLD based on oral bioavailability ≥30% and drug-likeness ≥0.18 via the TCMSP platform. We further establish a dataset containing 315 CAG targets from PharmGkb, GeneCard, OMIM, DrugBank database, and Therapeutic Target database. Network pharmacology found that there are 110 active components of MLD and 26 potential targets for CAG in the "ingredient-target" network. The results of gene ontology analysis show that these targets are involved mainly in reactive oxygen species metabolic process, regulation of vasculature development, and T cell activation. KEGG pathways analysis indicates that these signaling pathways in the treatment of CAG include HIF-1 signaling pathway, neurodegeneration-multiple diseases pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. Finally, docking of the active component quercetin and clinical medicine Omeprazole with the core targets was carried out. We found that quercetin, a crucial active ingredient in MLD, has good binding activity with potential targets of CAG, and its molecular conformation is stable, which is better than the binding energy of Omeprazole. So, the active ingredients of MLD exhibit good potential drugs for the treatment of CAG.
虽然加味六君子汤(MLD)在临床上对慢性萎缩性胃炎(CAG)有良好疗效,但其活性成分的鉴定及药理分子机制仍不清楚,亟待解决。本研究通过中药系统药理学数据库与分析平台(TCMSP),基于口服生物利用度≥30%和类药性≥0.18筛选出MLD的170种活性成分。我们进一步建立了一个数据集,包含来自PharmGkb、GeneCard、OMIM、DrugBank数据库和治疗靶点数据库的315个CAG靶点。网络药理学研究发现,在“成分-靶点”网络中,MLD有110种活性成分和26个CAG潜在靶点。基因本体分析结果表明,这些靶点主要参与活性氧代谢过程、血管发育调控和T细胞活化。京都基因与基因组百科全书(KEGG)通路分析表明,这些治疗CAG的信号通路包括缺氧诱导因子-1(HIF-1)信号通路、神经退行性变-多种疾病通路、丝裂原活化蛋白激酶(MAPK)信号通路和磷脂酰肌醇-3激酶/蛋白激酶B(PI3K-Akt)信号通路。最后,将活性成分槲皮素和临床药物奥美拉唑与核心靶点进行对接。我们发现,槲皮素作为MLD中的关键活性成分,与CAG潜在靶点具有良好的结合活性,其分子构象稳定,优于奥美拉唑的结合能。因此,MLD的活性成分在治疗CAG方面显示出良好的潜在药物特性。