Baicalin Induces Mesenchymal-Epithelial Transition in Chronic Pancreatitis Through Upregulation of E-Cadherin.

Abstract

Introduction: Baicalin has achieved the potential in the treatment of chronic pancreatitis (CP).To explore the potential of Baicalin on the induction of mesenchymal-epithelial transition (MET) in chronic pancreatitis.

Materials: To explore the causal association between CP and E-cadherin through bidirectional Mendelian randomization (MR). CDH1, the encoding gene of E-cadherin, we used weighted gene co-expression network analysis (WGCNA) to obtain CDH1-related genes in fibroblasts with CP. To predict the targets of Baicalin through SwissTargetPrediction. Molecular docking and molecular dynamics simulations were used to validate the binding of Baicalin and its targets.

Results: E-cadherin is a protective factor against CP, and the results indicated that NQO2 may be the key to Baicalin treating CP by regulating E-cadherin. Molecular docking results showed that the binding energy of binding baicalein to NQO2 is -11.7 kJ/mol. Molecular dynamics simulations indicated that baicalein and NQO2 interact with each other through van der Waals and Coulomb forces, and CDH1 and NQO2 interact with each other through hydrogen bonds.

Discussion: This study confirmed the causal relationship between E-cadherin and CP, providing a mechanistic explanation for the efficacy of Baicalin in CP. Although Baicalin could not directly bind to CDH1, we revealed its potential to indirectly restore E-cadherin by interacting with NQO2, a gene associated with CDH1 identified in CP fibroblasts. Baicalin-NQO2-CDH1 presented a novel axis treating CP. However, limitations include reliance on public data; the validation is still required.

Conclusion: Baicalin has the potential in the treatment of CP by inducing pancreatitis fibroblasts MET.