Background: Zhulingtang (ZLT), a traditional Chinese medicine formula, was used to evaluate the antilithic effects of experimentally induced calcium oxalate (CaOx) nephrolithiasis in ethylene glycol (EG)-fed rats. Materials and Methods: A total of 35 male Sprague-Dawley rats were randomly divided into 4 groups. Rats in group 1 (n = 8) served as the normal control. Rats in group 2 (n = 11) were treated with gastric gavages of starch as placebo and 0.75% EG as a stone inducer. Rats in group 3 (n = 8) were given 0.75% EG and a low dose (305 mg/kg) of ZLT. Rats in group 4 (n = 8) were treated with EG and a high dose (915 mg/kg) of ZLT. Twenty-four-hour urine and blood samples were collected at the beginning and at the end of the experiment for biochemical analysis. The histological appearances of the kidneys were observed under a polarized light microscope, and the crystal deposits were evaluated by a semiquantitative scoring method, computer assisted with ImageScoring software. Results: Our results revealed that rats fed with 0.75% EG for 4 weeks successfully produced renal deposition of CaOx. The severities of crystal deposition were significantly reduced in the 2 ZLT-fed groups compared with the placebo group (p = 0.025 and 0.047, respectively). Rats in the low-dose ZLT and placebo groups exhibited significantly lower serum phosphorus in comparison with the control rats (p = 0.005 and 0.03, respectively). Rats of the placebo group (EG + starch) encountered growth retardation, with their body weights slowly increasing, expressed as 160.63 ± 23.06 g, compared with 179.63 ± 13.41 g in normal rats (p < 0.001). Conclusion: ZLT reduced the severity of CaOx crystallization and slowed down the body weight loss effects. Therefore, the traditional Chinese medicine herbal formula ZLT may be an effective reagent for renal stone prophylaxis. Although the mechanism of ZLT in crystal inhibition remains unclear, macromolecules may be involved.

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