Potential Mechanisms Responsible for the Antinephrolithic Effects of an Aqueous Extract of Fructus Aurantii

The potential effects of Fa extract on the prevention and treatment of CaOx nephrolithiasis were analyzed in an ethylene glycol- (EG-) induced CaOx crystallization model in rats and an in vitro assay. Multiple biochemical variables were measured in the urine and kidney. Kidney sections were subjected to histopathological and immunohistochemical analyses. Urolithiasis-related osteopontin (OPN) was evaluated by Western blotting. The in vitro assay revealed the significant inhibition of crystal formation (3.50 ± 1.43) and dilution of formed crystals (12.20 ± 3.35) in the group treated with 1 mg/mL Fa extract compared with the control group (52.30 ± 4.71 and 53.00 ± 4.54, resp.) (p < 0.05). The in vivo experiments showed that prophylactic treatment with Fa aqueous extract significantly prevented EG-induced renal crystallization and pathological alterations compared with nephrolithic rats (p < 0.05). Significantly lower levels of oxidative stress, oxalate, and OPN expression as well as increased citrate and urine output levels were observed in both the low- and high-dose prophylactic groups (p < 0.05). However, in the low- and high-dose therapeutic groups, none of these indexes were significantly improved (p > 0.05) except for urinary oxalate in the high-dose therapeutic groups (p < 0.05). Fa extract prevented CaOx crystallization and promoted crystal dissolution in vitro. Additionally, it was efficacious in preventing the formation of CaOx nephrolithiasis in rats.