A novel cycloastragenol-encapsulated carboxymethyl chitosan-silk fibroin hydrogel combined with sucralfate alleviates MNNG-induced chronic atrophic gastritis by targeting HIF-1α and VEGF signaling pathways.

In order to treat chronic atrophic gastritis (CAG) caused by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the present study successfully fabricated a carboxymethyl chitosan (CMC)-silk fibroin (SF) hydrogel encapsulating cycloastragenol (Cyl) and sucralfate (SC) (Cyl-SC@SF/CMC). This represents a substantial improvement in drug delivery and therapeutic efficacy. The SEM analysis shows the porosity of fabricated Cyl-SC@SF/CMC revealed a network of pores inside the hydrogel. Thermogravimetric and rheological investigations confirmed that the hydrogel was the structure of SF and CFC forming intermolecular hydrogen bonds. A model was developed to stimulate the impact of MNNG on gastric epithelial cells. Furthermore, cell counting kit-8 (CCK-8) assay was employed to evaluate the viability and proliferation of MNNG induced CAG in GES-1 after exposed to fabricated Cyl-SC@SF/CMC hydrogels. The results displayed that Cyl-SC@SF/CMC is superior than SC@SF/CMC in promoting the growth of GES-1 cells while simultaneously reducing MNNG-triggered damage to GES-1 cells and mitochondrial dysfunction. Moreover, cell migration and invasion analysis revealed that Cyl-SC@SF/CMC significantly enhanced migration and suggesting its role in tissue repair and regeneration. Moreover, in CAG rats, Cyl and SC in the hydrogel exerted therapeutic effects by considerably reducing histological damage in gastric tissues as evidenced by histopathological examinations. Furthermore, the pharmacokinetics analysis showed that Cyl-SC@SF/CMC formulation exhibited a higher area under the curve (AUC) and longer mean residence time (MRT) in both blood and gastric tissues compared to SC@SF/CMC, suggesting enhanced therapeutic efficacy. Due to the importance of tumor-induced angiogenesis in the advancement of inflammation and malignance, this study also examines the levels of mRNA and protein expression of the HIF-1α and VEGF signaling pathways in vivo using Western blot qRT-PCR analysis.