In silico and in vivo anti-hyperuricemic and anti-gouty arthritic effects of Adhatoda vasica extract: Forecasting drug candidates and mechanistic insights into urate transporter 1 and xanthine oxidase inhibition

• Adhatoda vasica may be suggested as a promising potential to treat hyperuricemia and gouty arthritis for its anti-inflammatory and antioxidant properties • Adhatoda vasica alleviates hyperuricemia and gouty arthritis by inhibiting urate transporter 1 and xanthine oxidase • Adhatoda vasica also reveals a protective effect against hyperuricemia and gouty arthritis induced renal damage • Twenty-one Adhatoda vasica phytochemicals are identified via FT-IR and GC‑MS, four of which demonstrate strong binding affinities to URAT1 and XO, coupled with favorable pharmacokinetics, confirmed drug‑likeness, and lower predicted toxicity than the standard hyperuricemic drug benzbromarone Adhatoda vasica is abundant in alkaloids and flavonoids that exhibit robust anti-inflammatory and antioxidant activity, underscoring its potential as a promising treatment for inflammatory ailments. Therefore, the present study sought to explore the therapeutic potential of ethanolic Adhatoda vasica extract in hyperuricemic and gouty arthritic rodents, which was further validated through a computer-aided mechanism. Hyperuricemia and gouty arthritis were induced with potassium oxonate and monosodium urate in the models. Serum creatinine and uric acid levels were assessed, alongside urate transporter 1 (URAT1) and xanthine oxidase (XO) expression of the rodents. Histological studies demonstrated nephroprotective and anti-inflammatory effects, characterized by improved renal morphology and reduced interleukin-6 expression in a dose-dependent manner. Phytochemicals were identified through in vitro, FT-IR, and GC-MS analysis, revealing 21 bioactive compounds belonging to various groups like phenol, alcohol, aldehyde, fatty acid, alkaloid, steroid, terpene, and nitrogen compounds. Four compounds (PubChem CIDs: 66099, 5282826, 9817754, and 534587) showed strong binding affinity in molecular docking analysis via BIOVIA Discovery Studio and DataWarrior. These candidates exhibited favorable pharmacokinetic profiles, drug-likeness, and low toxicity, as assessed by SwissADME, AdmetSAR, and ProToxII, surpassing the standard drug Benzbromarone. The result suggested that Adhatoda vasica may alleviate serum uric acid in hyperuricemia and gouty arthritis by inhibiting URAT1 and XO. Overall, Adhatoda vasica demonstrates notable potential as a natural therapeutic agent for hyperuricemia and gout, justifying additional exploration for use in drug development or as a dietary supplement.