Background:
Calcium oxalate (CaOx)–induced renal injury is a key pathogenic process in urolithiasis and contributes to progressive renal dysfunction. Renal tubular epithelial cell damage, oxidative stress, and lipid nephrotoxicity play central roles in crystal retention and stone formation. Phyllanthus niruri L. (PN), a traditional medicinal plant used in urolithiasis, has demonstrated renoprotective properties; however, its molecular mechanisms remain incompletely understood.
Objective:
To investigate the protective effects and underlying molecular mechanisms of Phyllanthus niruri against calcium oxalate–induced renal injury, with a focus on lipid metabolism–related pathways.
Methods:
Network pharmacology and transcriptomic analyses were employed to identify active compounds and potential therapeutic targets of PN. In vitro experiments were conducted using sodium oxalate–induced injury in human renal tubular epithelial (HK-2) cells, while in vivo validation was performed in a glyoxylate-induced CaOx mouse model. Molecular docking, western blotting, immunofluorescence, histology, and biochemical assays were used to evaluate target modulation and renal injury markers.
Results:
Twenty active compounds of PN were identified, with ellagic acid (EA) emerging as a key bioactive component. Network pharmacology revealed SQLE, HMGCS1, and SCD—key regulators of cholesterol synthesis and lipid metabolism—as putative therapeutic targets. EA demonstrated strong binding affinity to these targets in molecular docking studies. In both cell and animal models, EA significantly reduced CaOx-induced renal tubular injury, oxidative stress, lipid accumulation, and total renal calcium content. EA treatment downregulated the expression of SQLE, HMGCS1, SCD, and p53, while improving renal histology and biochemical markers without affecting serum creatinine adversely.
Conclusion:
Ellagic acid, a major active component of Phyllanthus niruri, exerts significant renoprotective effects against calcium oxalate–induced renal injury by modulating lipid metabolism and reducing oxidative stress and tubular damage. These findings provide mechanistic evidence supporting the role of Phyllanthus niruri as a protective adjunct in the prevention and management of urolithiasis-related renal injury.
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