Penning decoction ameliorated pyroptosis in mice with lipopolysaccharide-induced endometritis through inhibition of the TLR4/NF-κB/NLRP3 pathway.

Objectives: Endometritis, stemming from bacterial infection, manifests as persistent inflammation and may cause infertility. Penning decoction (PND) has been approved for clinical treatment of patients with endometritis. However, the mechanism by which it prevents endometritis remains unknown. This study aimed to examine the impact of PND on lipopolysaccharide (LPS)-induced endometritis and elucidate the underlying mechanisms involved.

Methods: Firstly, ultra-performance liquid chromatography‒quadrupole‒time‒of‒flight mass spectrometry (UPLC‒Q‒TOF‒MS) analysis, in which both positive and negative ion modes were used to identify the chemical compounds in PND, was performed. The antipyroptotic effects of PND were validated in LPS-induced endometritis mice. Additionally, mouse endometrial epithelial cells (MEECs) were used to explore the molecular mechanism of PND in serum in vitro.

Results: A total of 145 chemical compounds, including flavones, saponins, polysaccharides, alkaloids, and glycosides, were identified in positive and negative ion modes. The results showed that LPS could induce pyroptosis in endometritis in vivo and in vitro. Treatment with PND or serum containing PND could significantly ameliorate LPS-induced pyroptosis by inhibiting the activation of the TLR4/NF-κB/NLRP3 signaling pathway.

Conclusion: Our results demonstrated that PND may improve LPS-induced endometritis by inhibiting the TLR4/NF-κB/NLRP3 pathway, which provides a potentially effective drug for the clinical treatment of endometritis.