Phillyrin prevents calcium oxalate kidney stones through the PPARγ signaling pathway.

BACKGROUND: Nephrolithiasis is a significant health issue causing pain, hypertension, and chronic kidney disease. Phillyrin, a bioactive compound from Forsythia suspensa, may offer therapeutic benefits against these conditions. The study was focused on phillyrin efficacy on alleviating kidney stone formation and associated damage. METHODS: HK-2 cells were exposed to calcium oxalate (CaOx) to generate an in vitro kidney cell injury model. The kidney stones were induced in rats by 1% ethylene glycol and 2% ammonium chloride. Cell viability was assessed by CCK-8 assay. Cell apoptosis was detected by JC-1 mitochondrial membrane potential assay. ROS and MDA contents and the activity of SOD and GSH-Px were assayed using matched assay kits. Differentially expressed genes (DEGs) were identified by RNA sequencing (RNA-seq). RESULTS: Phillyrin significantly reduced CaOx-induced apoptosis and oxidative stress in HK-2 cells. Moreover, phillyrin repressed oxidative stress and renal crystal deposition in model rats of kidney stones. RNA-seq revealed DEGs in rat kidneys post-phillyrin treatment, suggesting involvement in key pathways. Phillyrin activated the PPARγ signaling pathway in kidney stone induced rats and CaOx-exposed HK-2 cells. Furthermore, the PPARγ antagonist GW9662 exerted a counteracting impact on phillyrin-mediated anti-apoptosis and anti-oxidative effects in CaOx-exposed HK-2 cells. CONCLUSION: The present study demonstrated that the potential efficacy of phillyrin on alleviating CaOx kidney stone formation and associated oxidative stress. PPARγ signaling is the possible mechanism of action of phillyrin in controlling nephrolithiasis-triggered apoptosis.