Bioactive Compounds from Carica papaya (Papaya) Fruit Peel Target Key Enzymes in Diabetes and Dyslipidemia: A Molecular Insight

Background: Diabetes mellitus is a chronic condition causing hyperglycemia and disrupted metabolism due to insulin deficiencies. The treatment strategies mainly include dietary regulation and scientific validation of traditional medicines. The objective of this research was to investigate the phytochemicals and assess the hypoglycemic and hypolipidemic effects of the ethanolic extract of Carica papaya fruit peel. Methods: After preliminary phytochemical investigation, the extract’s phytoconstituents were confirmed using liquid chromatography mass spectroscopy (LC-MS), equipped with an electrospray ionization source. Molecular docking was conducted to assess the potential antidiabetic and antihyperlipidemic effects of the identified ligands. The in vitro assays included spectrophotometric evaluation of α-amylase, α-glucosidase, and pancreatic lipase inhibition. Results: The LC-MS investigation revealed four principal bioactive compounds such as Longistylin C, Neohesperidin dihydrochalcone, Assamsaponin A, and Soyasaponin A1. The molecular docking with target proteins resulting in docking score between −6.7 and −11.3 kcal/mol. In vitro studies demonstrated the extract has α-amylase inhibition with IC 50 values of 0.089 mg/ml ( P < 0.05), α-glucosidase inhibition IC 50 values of 0.140 mg/ml ( P < 0.05), and pancreatic lipase inhibition IC 50 values of 279.6 µg/ml. Conclusions: C. papaya contains bioactive substances that exhibit potential antidiabetic and antihyperlipidemic effects by inhibiting the essential enzymes associated with diabetes and dyslipidaemia. In vitro experiments demonstrated concentration-dependent inhibition of α-amylase and α-glucosidase, with modest inhibition of pancreatic lipase, indicating C. papaya peel as a potential natural adjuvant for the management of metabolic diseases.