Ursolic Acid Alleviates Orchitis via Modulating Ferroptosis in Peritubular Myoid Cells of Testis

ABSTRACT Chronic stress adversely affects reproductive health, increasing susceptibility to pathologies such as orchitis. Additionally, the maintenance of iron homeostasis is essential for preserving the function of the testicles, and iron overload leads to lipid peroxidation and iron accumulation, which induces testicular cell ferroptosis. Ursolic acid (UA), a pentacyclic triterpenoid compound naturally occurring in various plants, exhibits therapeutic potential as an agent for inflammatory and chronic degenerative diseases. However, its involvement in orchitis and ferroptosis remains unclear. The aim of this research was to elucidate the impact of UA on ferroptosis in testicular inflammation. The histopathological data revealed inflammatory infiltration in the testicular tissues from accidently deceased adult forest musk deer (FMD) under chronic stress. In vitro, UA effectively attenuated tumor necrosis factor‐α (TNF‐α)‐induced inflammation. Additionally, UA suppressed ferroptosis through the regulation of the breakdown of excessive lipid peroxides, enhancement in the activity of antioxidant enzymes, and activation of intracellular iron metabolism. Taken together, the current study elucidates multi‐target and multi‐pathway therapeutic effects of UA on reproductive homeostasis. These findings highlight that UA may serve as a potential functional component in the prevention of chronic stress‐induced diseases.