Mechanistic and Translational Evaluation of a Flavonoid Lead from

ABSTRACT Urolithiasis is a recurrent renal disorder characterized by calcium oxalate crystal deposition, oxidative stress, inflammation, and renal epithelial injury. Despite available therapies, recurrence rates remain high. Bryophyllum pinnatum (Lam.) Oken, traditionally used in urinary disorders, contains bioactive flavonoids with reported antioxidant and diuretic properties. However, the specific flavonoid(s) responsible for anti-urolithiatic activity and their mechanistic pathways remain unidentified. This study aims to isolate and characterize a flavonoid lead compound from B. pinnatum and evaluate its anti-urolithiatic activity through in vitro crystal assays, renal epithelial cell protection studies, and an ethylene glycol-induced rat model. Mechanistic pathways involving oxidative stress, inflammatory signaling, apoptosis, and renal transporter modulation will be explored. Translational biomarkers (KIM-1, NGAL, osteopontin) will be assessed to bridge preclinical findings with clinical relevance. The study is expected to validate a mechanistically defined phytopharmaceutical lead candidate for kidney stone prevention. Keywords: Urolithiasis, Bryophyllum pinnatum