Targeting diabetic pathways: In silico and in vivo study of bioactive compounds from Jatropha curcas leaf

The global burden of diabetes mellitus, a chronic metabolic disorder, is exceptionally high, particularly within Southeast Asia. The limitations and side effects of conventional therapies have driven interest in herbal alternatives such as Jatropha curcas. Utilizing both in silico and in vivo approaches, this research sought to determine how physic nut leaf extracts exert their antidiabetic effects and modulate pathways associated with diabetic microvascular complications. Phytochemicals from physic nut leaves were identified through databases and screened for drug-likeness (Rule of Five), pharmacokinetics, and toxicity. Promising compounds were further analyzed using network pharmacology to examine their roles in diabetes-related signalling pathways. In vivo validation was performed in 25 alloxan-induced diabetic Wistar rats, divided into five groups: control, standard (Metformin), and three extract doses (600, 900, and 1,200 mg/kg body weight), administered for 2 weeks. Outcomes measured included blood glucose levels (pre- and post-treatment) and Vascular Endothelial Growth Factor (VEGF levels). In silico results highlighted several bioactive compounds, including Jatrophone, Jatrophatrione, and its isomers. The C-1 epimer of Jatrophatrione may modulate diabetes-related pathways, particularly GPCR (G Protein-Coupled Receptors)-associated signalling involving AKT1 (Protein Kinase B alpha), with favourable safety and pharmacokinetic profiles. The in vivo approach showed that the extract at 1,200 mg/kg BW revealed the greatest reduction in blood glucose and serum VEGF levels, suggesting potential antihyperglycemic activity and possible modulation of pathways associated with diabetic microvascular complications. Overall, physic nut leaf extract demonstrated promising antidiabetic potential in the present experimental model.