Astragaloside IV Alleviates Trueperella pyogenes-Induced Endometritis via the Nrf2/HO-1 Signaling Pathway

The increasing antimicrobial resistance of <i>T. pyogenes</i>, one of the principal pathogens associated with endometritis, presents a formidable challenge in veterinary medicine. Astragaloside IV (AS-IV) is a triterpene saponin compound isolated from the traditional Chinese medicine Astragalus membranaceus. While recognized as the primary bioactive constituent of Astragalus membranaceus with diverse pharmacological properties, its potential to counteract <i>T. pyogenes</i>-induced endometritis has yet to be elucidated. In the current study, <i>T. pyogenes</i> infection models were successfully established in both mouse uteri and cultured goat endometrial epithelial cells (gEECs). Integrating histopathology, molecular biology and transcriptomic technology, this study characterized the multifaceted biological effects of AS-IV. Transcriptomic analysis indicates that the regulatory effects of AS-IV on <i>T. pyogenes</i>-induced infection are primarily associated with the enrichment of signaling pathways related to inflammation, apoptosis, and oxidative stress. Subsequent validation demonstrated that AS-IV treatment effectively alleviated <i>T. pyogenes</i>-induced endometrial damage by suppressing inflammation, apoptosis, and oxidative stress. These effects were mediated through Nrf2 and its downstream target HO-1, a mechanism further confirmed by the loss of protection upon Nrf2 inhibition. In summary, AS-IV protects the endometrium against <i>T. pyogenes</i>-induced inflammatory and oxidative damage by activating the Nrf2/HO-1 signaling pathway.