Piper attenuatum leaves extract reduced renal crystallization formation in urolithiasis might be due to probable interaction with uromodulin protein: An evidence based in vivo and in silico studies

Urolithiasis can cause excruciating pain and hardly managed by allopathic medicine without surgery. Recently, many of research on validation of traditional medicinal plants provided a hope for management of urolithiasis. In this context, we have found a gap between traditional claims and scientific validation on use of Piper attenuatum (P. attenuatum) towards mangement of renal caliculi. Therefore, present study was planned to determine anti-urolithiatic efficacy of ethanol extract of P. attenuatum (EEPA) leaves on ethylene glycol induced urolithiasis on male Wistar rats. Further, study pertaining to phytochemical analysis followed by molecular docking of selected bioactive phytochemicals of P. attenuatum against human uromodulin (a key potential biomarkers relevant for renal function and chronic kidney disease including urolithiasis) protein. As a result, EEPA (400 mg/kg/bw) was found to significantly improves various urinary (volume: 7.19 ± 0.11 ml/24 hr; calcium: 6.15 ± 0.51 mg/dl; phosphate: 7.83 ± 0.56 mg/dl and oxalate: 1.78 ± 0.03 mg/dl) and serum parameters (creatinine: 1.85 ± 0.04 mg/dl; uric acid: 1.65 ± 0.08 mg/dl and blood urea nitrogen or BUN: 32.20 ± 1.41 mg/dl), when compared with negative control group followed by reverse in changes as an evidence of histological studies. Additionally, molecular docking studies revealed higher binding affinity to some selected phytoconstituents against human uromodulin enzyme. It was further concluded that EEPA leaves exhibits significant antiurolithiatic activity due to presence of aristolactam A II, cepharadione A and B, piperolactam A, norcepharadione B and pipoxide chlorohydrin via strong binding efficiency with uromodulin protein.