Methanol extract from Apium graveolens stimulate glucagon-like peptide-1 secretion (GLP-1), reduced dipeptidyl-peptidase-4 (DPP-4) and protect pancreatic b cells against glucotoxicity and H2O2 toxicity

Introduction: Glucagon-like peptide-1 (GLP-1) plays a critical role in glucose regulation by stimulating insulin secretion in a glucose-dependent manner. It enhances the functionality of pancreatic β-cells, minimizing apoptotic signals while promoting their proliferation and neogenesis. Consequently, leveraging plant-based GLP-1 agonists offers a promising approach to mitigating hyperglycemia in individuals with type 2 diabetes. This study aimed to explore the potential of methanol extract from Apium graveolens (commonly known as celery) to enhance insulin secretion, inhibit dipeptidyl peptidase-4 (DPP-4), and boost GLP-1 levels. Furthermore, it assessed celery's ability to protect pancreatic β cells against glucotoxicity and H2O2-induced toxicity in vitro. Additionally, we sought to identify the flavonoids present in the crude ethanolic extract of celery through HPLC/MS analysis. Methods: We assessed cell viability, cell integrity (using lactate dehydrogenase (LDH) leakage assay), mitochondrial function (via ATP production), and insulin secretion in INS-1 pancreatic β-cells. GLP-1 activation and insulin sensitivity were evaluated in GLUTag cells, while DPP-4 activity was measured using an in vitro inhibitory assay. Results: HPLC/MS analysis revealed the presence of 11 phenolic compounds in celery. Treatment with varying concentrations of celery extract (100, 125, 150, 200 µg/mL) resulted in decreased cell death, significantly improved cell viability, and increased cellular ATP levels, thereby offering protection against glucotoxicity and H2O2-induced toxicity. Additionally, it boosted insulin production and reduced insulin resistance. The inhibitory effect of celery extract on DPP-4 activity, coupled with the increase in GLP-1 halflife, enhances insulin secretion from β cells, outlining celery's potential hypoglycemic mechanism. Conclusion: The findings of this study underscore celery's therapeutic potential as a treatment option for individuals with type 2 diabetes, attributing to its ability to modulate insulin secretion, enhance pancreatic β-cell survival, and inhibit DPP-4, thereby increasing GLP-1 levels. This illuminates a promising avenue for further research and potential diabetes management strategies.