Integrated experimental and network pharmacology evaluation of a defined phytochemical combination in diabetes-related models

Aim This study evaluated a predefined combination of curcumin, quercetin, forskolin, and gymnemic acid using both experimental and computational approaches. Methods The phytochemical combination of curcumin, quercetin, forskolin, gymnemic acid was assessed through diabetes-related enzyme inhibition and free radical scavenging assays. Acute and 90-day oral toxicity studies were conducted to evaluate safety. Two independent cohorts of rats induced with streptozotocin one over 120 days and the other over 90 day- were used to examine outcomes related to glycaemia, biochemistry, oxidative stress, inflammation, histology, and pancreatic insulin-immunoreactivity outcomes. Network pharmacology and molecular docking methods were employed to generate mechanistic hypotheses. Results PCC inhibited the activities of α-amylase, α-glucosidase, DPP-IV, and aldose reductase. Inhibition of glucose-6-phosphatase, PTP1B, cholesterol esterase, and pancreatic lipase was minimal or undetected. PCC demonstrated scavenging activity against DPPH and ABTS radicals. No consistent treatment-related toxicity was observed during the 90 days of dosing at doses up to 600 mg/kg/day, the highest tested. Both streptozotocin cohorts showed that PCC improved glycaemia and some selected metabolic and oxidative stress measures, as well as pancreatic insulin immunoreactivity and inflammatory markers; however, these findings do not indicate β-cell regeneration or a mechanism for type 2 diabetes. Network and docking analyses generated only predicted associations. Conclusion The predefined PCC exhibited selective inhibition of diabetes-related enzymes, demonstrated free radical scavenging activity, and showed preliminary effects in vivo . The computational findings are exploratory but hypothesis-generating and require pharmacokinetic and molecular validation. Neither synergy nor direct engagement of the predicted molecular targets was established.