Exploring the Mechanism of Shi-San-Wei-He-Zhong-Wan in the Treatment of Functional Dyspepsia Based on Network Pharmacology and Experimental Validation

Purpose: The incidence of Functional Dyspepsia (FD) is gradually increasing, yet there are currently no effective treatment methods available. This study explored the effective components, potential targets, and pathways of Shi-San-Wei-He-Zhong-Wan (SSWHZW) in the treatment of FD, aiming to provide new insights into its treatment. Methods: First, the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and GeneCards databases were utilized to identify the major active components of SSWHZW and potential therapeutic targets of FD. Subsequently, functional enrichment analyses were performed to elucidate the mechanisms of SSWHZW on FD. Molecular docking simulations were then conducted to assess the binding affinity of key targets and major active components. Next, an FD animal model was established, and the therapeutic effects of SSWHZW were validated using Hematoxylin and Eosin (HE) staining and Enzyme-linked Immunosorbent Assay (ELISA). Finally, Western blot analysis was performed to validate the involvement of key signaling pathways. Results: A total of 229 active ingredients and 283 putative targets were identified from SSWHZW, of which 173 overlapped with the targets of FD and were considered potential therapeutic targets. Key ingredients, such as quercetin, kaempferol, wogonin, and baicalein, were identified as pivotal components of SSWHZW, potentially acting on the 173 overlapping targets and influencing FD through related signaling pathways. Functional enrichment analysis revealed that the PI3K-Akt signaling pathway, VEGF signaling pathway, and NF-kappa B signaling pathway may be involved in the mechanism of SSWHZW in treating FD. Molecular docking predicted that all five ingredients could firmly bind with the top-ranked target TP53 in the Protein- protein Interaction (PPI) network. Further experiments demonstrated that SSWHZW protected the intestinal tissues of FD rats from inflammatory damage by inhibiting the PI3K/AKT signaling pathway. Conclusion: Based on network pharmacology, this study explored the multi-component, multitarget, and multi-pathway characteristics of SSWHZW in treating FD. The findings suggest that SSWHZW exerts its anti-FD effects by inhibiting the expression of the PI3K/AKT signaling pathway, providing new insights and methods for further research on the mechanism of SSWHZW in treating FD.