Synergistic Nephroprotective and Litholytic Efficacy of Sonchus arvensis and Orthosiphon stamineus: An LC-MS Profiling, In Silico, and In Vivo Study

Kidney stone disease remains a global health challenge characterized by high recurrence rates, necessitating alternative therapies from natural products. Sonchus arvensis and Orthosiphon stamineus contain bioactive flavonoids with antioxidant, anti-crystallization, and nephroprotective properties; however, their combined synergistic litholytic potential remains underexplored despite prevalent traditional use. This study evaluated the anti-nephrolithiasis potential of combined S. arvensis and O. stamineus leaf extracts using in silico and in vivo approaches. Leaves were extracted with ۷۰% ethanol, and major bioactive compounds were identified via UPLC-MS/MS for phytochemical profiling. Molecular docking targeted glycolate oxidase (PDB ID ۲YVS). In the in vivo study, ethylene glycol-induced urolithiasis rats received oral treatments for ۱۴ days at varying combination ratios. Renal function biomarkers and kidney weight index were assessed via parametric and non-parametric statistics. The ۱:۱ ratio proved most efficacious, significantly reducing serum creatinine, blood urea nitrogen (BUN), and urea to near-normal levels (p < ۰.۰۵). This was accompanied by a ۲۸.۵% reduction in the kidney weight index, indicating attenuation of renal hypertrophy and edema. These in vivo outcomes were corroborated by in silico multi-target synergy analysis. Specifically, Artemisitene from O. stamineus demonstrated a stable binding affinity (-۷.۳۴ kcal/mol), while Epiandrosterone from S. arvensis exhibited potent molecular interaction with a predicted inhibition constant (Ki) of ۳۸۶ nM, supported by robust hydrogen bonds and van der Waals forces. In conclusion, the ۱:۱ S. arvensis and O. stamineus ethanolic extract formulation represents the most optimal synergistic combination for renal stone dissolution and cellular protection, offering a highly effective candidate for nephrolithiasis therapy.

کلیدواژه ها:

Litholytic efficacy ، Sonchus arvensis ، Orthosiphon stamineus ، LC-MS ، Molecular docking