Total flavonoids of Grona styracifolia (Osbeck) H.Ohashi and K.Ohashi capsules alleviate renal urolithiasis by modulating autophagy and endoplasmic reticulum stress.

BACKGROUND: Calcium oxalate nephrolithiasis represents the most common form of kidney stone disease, characterized by limited therapeutic interventions and a high rate of recurrence. Grona styracifolia (Osbeck) H.Ohashi and K.Ohashi [syn.: Desmodium styracifolium (Osbeck) Merr.; Fabaceae], a traditional Chinese medicinal plant has been empirically used to treat urolithiasis; however, the mechanisms underlying its efficacy remain poorly elucidated. OBJECTIVE: To investigate the anti-lithogenic mechanisms of total flavonoids of G. styracifolia capsules (DS) in calcium oxalate (CaOx) crystal deposition and their renal-associated injury. METHODS: Sprague-Dawley rats were subjected to an ethylene glycol-induced CaOx nephrolithiasis model. The animals received DS treatment (50, 100, and 200 mg/kg) for 1 month. Thereafter, Renal histopathology was evaluated using hematoxylin and eosin staining. Furthermore, biochemical parameters such as calcium, inorganic phosphorus, creatinine, and urea nitrogen levels were assessed. Endoplasmic reticulum stress markers and autophagy-related proteins were assessed using quantitative PCR and Western blotting. RESULTS: The DS treatment significantly reduced CaOx crystal deposition and the associated renal injury compared to untreated controls. In addition, treated animals demonstrated improved renal function, as evidenced by decreased levels of calcium, creatinine, inorganic phosphorus, and urea nitrogen. Histological examination revealed attenuated renal fibrosis and improved kidney morphology. Mechanistic investigations have indicated that the administration of DS is linked to the modulation of endoplasmic reticulum stress and autophagy, processes that are disrupted by the formation of kidney stones and urinary obstruction. CONCLUSION: The DS significantly mitigate CaOx nephrolithiasis by modulating endoplasmic reticulum stress and autophagy. This finding highlights its traditional therapeutic application and suggests its potential development as a phytotherapeutic agent for the prevention of kidney stones.