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

## TL;DR

Astragaloside IV, a compound from traditional Chinese medicine, protects against endometritis caused by T. pyogenes by reducing inflammation and oxidative stress through the Nrf2/HO-1 pathway.

## Contribution

This study is the first to demonstrate that Astragaloside IV alleviates T. pyogenes-induced endometritis via the Nrf2/HO-1 signaling pathway.

## Key findings

- AS-IV reduces T. pyogenes-induced endometrial damage by suppressing inflammation, apoptosis, and oxidative stress.
- Transcriptomic analysis shows AS-IV's effects are linked to inflammation, apoptosis, and oxidative stress pathways.
- Nrf2 and HO-1 mediate the protective effects of AS-IV, confirmed by Nrf2 inhibition experiments.

## Abstract

The increasing antimicrobial resistance of T. pyogenes, 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 T. pyogenes-induced endometritis has yet to be elucidated. In the current study, T. pyogenes 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 T. pyogenes-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 T. pyogenes-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 T. pyogenes-induced inflammatory and oxidative damage by activating the Nrf2/HO-1 signaling pathway.