Background. 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. Methods. 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. Results. 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. Conclusions. 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.

Objectives. Systematic reviews/meta-analyses (SRs/MAs) are still controversial on the effectiveness of Banxia Xiexin decoction (BXD) to treat gastroesophageal reflux disease (GERD). To assess the evidence reliability and inform the clinical use of BXD, we performed a meta-analysis from previous SRs/MAs to collate, critically appraise, and synthesize the effectiveness of BXD treatment in GERD. Methods. SRs/MAs were collected by searching major medical databases. The included studies were evaluated in terms of methodological quality and quality of evidence using criteria from the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system, respectively. Results. Six SRs/MAs were included in this study. The methodological quality of SRs/MAs was generally unsatisfactory. Unregistered protocols, failure to provide a list of excluded trials, and lack of a comprehensive search strategy were the main limitations of previous SRs/MAs. No high-quality evidence was found to support the effect of BXD on GERD patients. The qualitative data synthesis relied on low-quality trials with a small sample size, which was the main factor for evidence degradation. Conclusions. BXD seems to have promising efficacy to treat GERD patients. Although the quality of SRs/MAs was generally low and defects were frequent, our study highlights areas where methodologies need to be improved.