Exploring the Protective Mechanisms of Chayote (<i>Sechium edule</i>) Juice in Mitigating Streptozotocin‐Induced Pancreatic Dysfunction

ABSTRACT Chayote ( Sechium edule ) has been traditionally used in Mexico to manage diabetes, owing to its hypoglycemic, anti‐oxidant, and anti‐inflammatory properties. However, the specific effects and mechanisms of chayote juice (SEJ) in preventing pancreatic dysfunction remain underexplored. This study investigated the pancreatic protective effects and underlying mechanisms of SEJ in multiple low‐dose streptozotocin (MLD‐STZ)‐induced diabetic mouse model and H 2 O 2 ‐treated mouse insulinoma cell line (MIN‐6). C57BL/6 mice were administered MLD‐STZ to induce pancreatic dysfunction and treated with SEJ. Diabetic parameters, pancreatic islet morphology, and protein expressions were evaluated. H 2 O 2 ‐treated MIN‐6 cells were used to assess SEJ's protective mechanisms at the cellular level. Molecular docking studies were performed to elucidate interactions between SEJ phenolic compounds and key proteins involved in oxidative stress. SEJ significantly preserved pancreatic islet structure and insulin levels, reducing blood glucose levels. Mechanistically, SEJ suppressed the expression of apoptosis markers (caspase‐3, PARP, BAX) and inflammatory markers (NF‐κB, iNOS, NLRP3) in the pancreas and MIN6 cells, indicating protection of the pancreas and β‐cells. Furthermore, SEJ upregulates endogenous anti‐oxidant proteins (Nrf‐2, HO‐1), which are essential for mitigating oxidative stress‐induced cell stress in diabetes circumstances. Molecular docking indicated that vicenin‐2 in SEJ exhibit strong binding affinities to KEAP‐1, Nrf‐2, and HO‐1 proteins. SEJ demonstrates substantial pancreatic protective effects through its anti‐oxidant, anti‐apoptotic, and anti‐inflammatory actions. These findings suggest that chayote juice could be developed as a functional food for diabetes management.