Network pharmacology study and preclinical validation highlight the anti-diabetic potential of Persicaria...

Persicaria lapathifolia (L.) Delarbre is a widely distributed species found across Asia, Africa, and Europe, including northeastern India, and has been reported to exhibit antioxidant potential and in-vitro anti-diabetic activity. This study aimed to perform comprehensive phytochemical characterization, network pharmacology analysis, and preclinical validation to investigate the anti-diabetic potential of P. lapathifolia leaf extract. The prepared extract was characterized for GC-MS, LC-MS, HPTLC, and FTIR. Network pharmacology (Cytoscape) identified key bioactive targets, which were validated in-vitro via glucose uptake, GLUT4 translocation, and AMPK/Akt activation. Acute oral toxicity was assessed as per OECD 425 guidelines to ensure safety. For in-vivo evaluation, diabetes was induced in rats using streptozotocin (STZ, 55 mg/kg b.w., i.p.). Animals were then treated for 21 days with either a low-dose (66.6 mg/kg b.w., p.o.), a high-dose (200 mg/kg b.w., p.o.) of the extract, or metformin (5 mg/kg b.w., p.o.). Following treatment, animals were evaluated biochemically and histopathologically. Phytochemical profiling confirmed the presence of key bioactive compounds, including Quercetin and Kaempferol. Network pharmacology revealed 357 common targets associated with diabetes, with strong involvement of AMPK and Akt signaling pathways. In-vitro, the extract enhanced glucose uptake, promoted GLUT4 translocation, and activated AMPK/Akt pathways. In-vivo, it notably lowered blood glucose, preserved lipid levels, and restored liver and pancreatic structure without toxicity, showing efficacy similar to metformin. Overall, these findings highlight that P. lapathifolia shows strong potential as a natural anti-diabetic agent, warranting further studies to isolate its active constituents and elucidate the underlying mechanisms.