Safety evaluation of ursolic acid: Absence of acute oral and reproductive toxicity in a rodent model.

Ursolic acid (UA), a natural pentacyclic triterpenoid, exhibits diverse pharmacological activities including anti-inflammatory, antioxidant, and anti-hyperglycaemic effects. More recently, its potential applications in hepatoprotection and anticancer therapy have garnered significant interest. However, its reproductive toxicity profile remains inadequately characterized and inconsistent across studies. This study aimed to evaluate the acute oral toxicity of UA and its effects on male reproductive organ histopathology and sperm quality parameters (motility, viability, morphology) in rodents. Acute oral toxicity was first determined using a limit test at 12,500 mg kg-1 body weight. For the reproductive toxicity study, male Sprague-Dawley rats were administered UA at doses of vehicle (0.5 % CMC-Na), 125 or 250 mg kg-1 UA for 30 days. A positive-control group received cyclophosphamide (40 mg kg-1 day-1) for 5 days. Sperm motility, viability and morphology were evaluated, and the reproductive organs were examined histopathologically. Results show that no treatment-related mortality or clinical signs were observed in the UA-treated animals. Sperm parameters and testicular architecture remained unchanged across UA groups compared with controls, with normal spermatogenesis and absence of lesions. In contrast, cyclophosphamide-induced significant reductions in sperm motility and concentration. These results demonstrate that UA does not induce reproductive toxicity under the conditions tested (250 mg kg-1 day-1) providing a toxicological basis for its safe use.