The potential of pharmacological activities of the multi-compound treatment for GERD: literature review and a network pharmacology-based analysis

The prevalence of gastroesophageal reflux disease (GERD) is rapidly increasing due to the adoption of a Westernized lifestyle; at the same time, safe and efficient treatment is required due to the side effects and refractoriness of proton pump inhibitors (PPIs). The frequently used multi-compound treatment for GERD in the current traditional Korean medicine (TKM) clinical field comprises Crassostrea gigas Thunberg shell (CGTS), Bambusae Caulis in Taeniam (BCT), Ponciri Fructus Immaturus (PFI), Scutellaria baicalensis Georgi (SBG), medicated leaven (ML) and Glycyrrhizae Radix et Rhizoma (GRR). The current review was based on “Kun-Shin-Choa-Sa” theory and network analysis was conducted to explore the potential pharmacological activities, including efficacy and mechanisms of action of multi-compound treatment against GERD. Hypergeometric test results showed that the targets of multi-compound treatment are significantly associated with GERD gene sets, consistent with the literature review findings. In particular, the enrichment analysis indicated that the SBG targets are related to the IL-17 signaling pathway, bile secretion, small-cell lung cancer, and non-small cell lung cancer, corroborating the literature review, particularly concerning anti-inflammatory effect. In the literature review, CGTS and BCT, classified as “Kun,” play a role in anti-acid, anti-inflammatory, and anti-oxidative effects. The complementary “Shin” herbs, PFI and SBG, showed functions related to improving the prolonged gastric emptying rate, peristalsis, and a gastric cytoprotective effect. With the role of “Choa,” ML was suggested to inhibit H. pylori growth and diminish gastric acid secretion, consistent with the gastric acid secretion pathway in the enrichment analysis. However, the enrichment analysis did not show any significantly related pathways for CGTS and PFI, which may reflect the lack of information in the KEGG database in terms of the link between GERD, its mechanisms, and the abundance of minerals in CGTS. Despite the pharmacological potential of multi-compound treatment, this study should be corroborated by well-designed future experimental studies.