Extracts of Aspidopterys tomentosa Attenuate Nephrolithiasis via Inhibiting Endoplasmic Reticulum Stress

Objectives: Aspidopterys obcordata has been traditionally used by the Dai people in Xishuangbanna, China, for the prevention and treatment of renal calculi. This study aimed to investigate the inhibitory effect of A. tomentosa extracts on calcium oxalate stone formation. Methods: The extracts of A. tomentosa (EA) were obtained via 95% ethanol reflux extraction, followed by multi-polar solvent extraction and elution. The HK-2 cell injury model induced by calcium oxalate and the renal calculus mouse model established by intraperitoneal injection of glyoxylic acid were established to assess drug efficacy. EA intervention was performed to evaluate its effects on calcium oxalate crystal deposition, renal tubular injury, cell apoptosis, and serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Furthermore, the potential mechanism underlying, particularly the regulation of PERK/ATF4/CHOP signaling pathway and endoplasmic reticulum stress-mediated apoptosis, was investigated. Results: EA treatment significantly reduced renal calcium oxalate crystal deposition, alleviated renal tubular injury, inhibited cell apoptosis, and decreased Scr and BUN levels. Mechanistically, the protective effects of EA were mediated by the downregulation of the PERK/ATF4/CHOP signaling pathway and the suppression of endoplasmic reticulum stress-mediated apoptosis. Conclusions: These findings provide experimental evidence supporting that A. tomentosa can be developed as a promising agent for the prevention of nephrolithiasis.