Biwa (Eriobotrya japonica) Leaf Nanoherbal for Diabetes Therapy: In Silico and In Vivo Study on Blood Glucose and Pancreatic Histology

Diabetes mellitus is a global metabolic disorder with an increasing prevalence. This study investigates the antidiabetic potential of Biwa (Eriobotrya japonica) leaf nanoherbal through in silico and in vivo approaches. A total of 12 bioactive compounds from E. japonica leaf extract were screened using in silico approaches to assess their pharmacokinetics, toxicity, and molecular interactions with PTP1B and DPP4. Molecular docking analysis revealed that 11 out of 12 compounds exhibited strong interactions with these key enzymes involved in glucose metabolism, particularly Quinic Acid (–7.7 kcal/mol) and Luteolin (–7.6 kcal/mol) for PTP1B, as well as Oleanolic Acid (–9.2 kcal/mol), Luteolin (–9.1 kcal/mol), and quercetin (–9.0 kcal/mol) for DPP4. For the in vivo study, 30 Wistar rats were divided into 5 groups, where the negative control [C(–)] received physiological saline, while the diabetic control [C(+)] and treatment groups were induced with alloxan (120 mg/kg BW). After diabetes induction, [T1] received E. japonica nanoherbal at 250 mg/kg BW, [T2] received E. japonica nanoherbal at 500 mg/kg BW, and [T3] received glibenclamide at 5 mg/kg BW. Blood glucose levels were monitored, and pancreatic histology was analyzed. The in vivo results showed that nanoherbal treatment significantly reduced blood glucose levels, with the 500 mg/kg BW dose decreasing glucose levels from 277.8 to 157.4 mg/dL on day 14. Histological analysis further demonstrated improved pancreatic islet structure and reduced cellular degeneration in treated groups. These findings suggest that E. japonica nanoherbal has strong antidiabetic potential by targeting glucose-regulating enzymes and enhancing pancreatic histology. HIGHLIGHTS Strong interactions were observed in the molecular docking analysis between the key bioactive compounds of japonica, where Quinic Acid and luteolin exhibited strong binding affinities with PTP1B, while Oleanolic Acid, luteolin, and quercetin showed high affinities for DPP4. A novel nanoherbal formulation enhanced the bioavailability and efficacy of E. japonica bioactive compounds for diabetes therapy. Extensive ADMET profiling ensured the safety and suitability of the bioactive compounds for long-term therapeutic applications. Significant glucose level reduction was achieved in diabetic rats, dropping from 277.80 to 157.40 mg/dL in 14 days with a 500 mg/kg BW dosage. At higher doses, enhanced cellular regeneration in pancreatic tissues was observed, indicating potential protective effects against pancreatic damage caused by diabetes. GRAPHICAL ABSTRACT