Computer-Assisted Screening of Active Compounds in Traditional Chinese Medicine Targeting SNX10 as a Promising...

Inflammatory bowel diseases (IBD) are chronic and recurrent gastrointestinal disorders affecting millions worldwide, imposing significant social and economic burdens. Safe and effective medications for IBD prevention and treatment are urgently needed. SNX10 has emerged as a potential therapeutic target, while traditional Chinese medicine (TCM) active compounds offer unique advantages in drug development due to their inherent safety and therapeutic properties. This study aimed to identify TCM compounds targeting SNX10 using molecular docking, molecular dynamics (MD) and MMGBSA binding free energy calculations. From a pool of 300 + TCM compounds, vitexin-4″-O-glucoside, scutellarin, diosmin and alpha-hederin were identified as promising candidates. Alpha-hederin exhibited the strongest binding affinity (-50.19 kJ/mol) via robust electrostatic and hydrophobic interactions, as revealed by MMGBSA, correlating with its superior efficacy in alleviating DSS-induced IBD in mice. Additionally, surface plasmon resonance (SPR) results showed that alpha-hederin can directly bind to SNX10 with a dissociation constant (Kd) of 3.02 μM. RNA-sequencing results show that alpha-hederin works by reducing inflammation and promoting gut cell proliferation. These findings not only propose novel TCM candidates for IBD management but also reinforce SNX10 as a therapeutic target and provide a scalable screening framework for TCM-based drug discovery.