Huang Jinke, Wang Yitian, Xu Peng, Liu Jiali, Ma Jinxin, Wang Yu, Liu Zhihong, Lv Mi, Wang Fengyun, Tang Xudong
Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Institute of Clinical Basic Medicine of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
Evid Based Complement Alternat Med. 2022 May 19;2022:2996865. doi: 10.1155/2022/2996865. eCollection 2022.
To investigate the pharmacological mechanism of Zhizhu pill (ZZP) against gastroesophageal reflux disease (GERD), network pharmacology in combination with molecular docking was applied in this study.
Active compounds of ZZP and target genes related to GERD were identified through public databases. Subsequently, the obtained data were used as a basis for further network pharmacological analysis to explore the potential key active compounds, core targets, and biological processes involved in ZZP against GERD. Finally, the results predicted by network pharmacology were validated by molecular docking.
Twenty active components of ZZP were identified to act on 59 targets related to GERD. Enrichment analysis revealed that multiple biological processes including response to oxygen levels, response to oxidative stress, and response to reactive oxygen species were involved in the GERD ZZP treatment with ZZP. ZZP had an impact on the prognosis of GERD mainly through the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and pathways in cancer. Further analysis identified the key components and core targets of ZZP against GERD, of which nobiletin, didymin, luteolin, and naringenin were key components, and PPARG, MMP9, JUN, TP53, PTGS2, EGFR, MAPK3, CASP3, AKT1, and VEGFA were the core targets. Molecular docking verified the stable bonds formed between the key components and the core targets.
The results of this study predict that the therapeutic effects of ZZP in GERD are mediated at least in part via PPARG, MMP9, JUN, TP53, PTGS2, EGFR, MAPK3, CASP3, AKT1, and VEGFA. These results may be useful in providing an experimental basis and new ideas for further research on ZZP in GERD.
为探讨枳术丸（ZZP）治疗胃食管反流病（GERD）的药理机制，本研究采用网络药理学结合分子对接的方法。
通过公共数据库鉴定ZZP的活性成分和与GERD相关的靶基因。随后，将获得的数据作为进一步网络药理学分析的基础，以探索ZZP治疗GERD潜在的关键活性成分、核心靶点和生物学过程。最后，通过分子对接验证网络药理学预测的结果。
鉴定出ZZP的20种活性成分作用于59个与GERD相关的靶点。富集分析显示，包括对氧水平的反应、对氧化应激的反应和对活性氧的反应等多个生物学过程参与了ZZP对GERD的治疗。ZZP主要通过缺氧诱导因子-1信号通路、磷脂酰肌醇-3激酶-蛋白激酶B信号通路和癌症相关通路对GERD的预后产生影响。进一步分析确定了ZZP治疗GERD的关键成分和核心靶点，其中川陈皮素、柚皮芸香苷、木犀草素和柚皮素是关键成分，过氧化物酶体增殖物激活受体γ（PPARG）、基质金属蛋白酶9（MMP9）、原癌基因蛋白（JUN）、肿瘤蛋白p53（TP53）、环氧合酶-2（PTGS2）、表皮生长因子受体（EGFR）、丝裂原活化蛋白激酶3（MAPK3）、半胱天冬酶3（CASP3）、蛋白激酶B（AKT1）和血管内皮生长因子A（VEGFA）是核心靶点。分子对接验证了关键成分与核心靶点之间形成的稳定结合。
本研究结果预测，ZZP对GERD的治疗作用至少部分是通过PPARG、MMP9、JUN、TP53、PTGS2、EGFR、MAPK3、CASP3、AKT1和VEGFA介导的。这些结果可能为进一步研究ZZP治疗GERD提供实验依据和新思路。
