Total flavonoids of Desmodium styracifolium attenuate nephrolithiasis via reducing calcium oxalate crystallization and renal inflammation

Introduction Desmodium styracifolium , known as Guangjinqiancao in Chinese, is a widely used traditional medicinal herb in Southern China for clearing heat and excreting dampness. It has been historically prescribed for the treatment of urological disorders, particularly urolithiasis (Shi Lin). While the clinical efficacy of D. styracifolium is well-documented, the precise mechanisms of its primary active fraction, total flavonoids of D. styracifolium (TFDS), regarding crystallization and inflammation remain to be fully elucidated. This study aims to investigate the therapeutic mechanism of TFDS in alleviating nephrolithiasis by systematically evaluating its effects on calcium oxalate (CaOx) crystallization kinetics, crystal-cell interaction, and renal inflammatory responses. Methods The inhibitory effects of TFDS on calcium oxalate monohydrate (COM) crystallization were quantified in vitro , assessing crystal nucleation and growth. Flow cytometry and microscopy were utilized to evaluate the effect of TFDS on crystal adhesion and endocytosis in renal tubular epithelial cells. RT-qPCR was used to assess the expression of inflammatory cytokines. Furthermore, an ethylene glycol and ammonium chloride-induced rat model of nephrolithiasis was employed to evaluate the anti-lithogenic effect of TFDS in vivo , utilizing ultrasonography, serum/urine biochemistry, and histopathological analysis. Results In vitro assays demonstrated that TFDS significantly inhibits COM crystal formation and growth in a dose-dependent manner. Notably, TFDS promoted the dissolution of pre-formed crystals and effectively blocked the adhesion and internalization of crystals by renal cells. Moreover, TFDS treatment suppressed the crystal-induced upregulation of pro-inflammatory cytokines (IL-6, IL-8, TNF-α). In vivo experiments demonstrated that the administration of TFDS significantly attenuated renal crystal retention, reduced tissue damage, and improved renal function. Conclusion TFDS exerts a potent anti-lithogenic effect by targeting multiple stages of the crystallization process—inhibiting crystal nucleation and growth, promoting dissolution, and preventing cellular adhesion and endocytosis,and suppressing associated inflammation. These findings provide a scientific cognition for the traditional use of D. styracifolium and elucidate the mechanism of action for TFDS-based therapies in managing nephrolithiasis.