Baicalin inhibits Listeria monocytogenes-induced embryonic loss through the JNK/NEK7-NLRP3/GSDMD pathway

Enhua Zhang1, Jing Chen1, Wen Liu1

  • 1School of Basic Medical Sciences, Hebei University, Baoding 071001, China.

PubMed
Abstract

Insights

Baicalin (BA) protects against Listeria monocytogenes (LM)-induced embryo loss by inhibiting the NLRP3 inflammasome pathway. This study reveals BA

Area of Science:

  • Immunology
  • Reproductive Biology
  • Pharmacology

Background:

  • Listeria monocytogenes (LM) infection can lead to embryo loss by activating the NLRP3 inflammasome at the maternal-fetal interface.
  • Baicalin (BA), derived from Scutellaria baicalensis, is known for its fetal-preserving properties.
  • The precise mechanism by which BA might counteract LM-induced embryonic loss remains unclear.

Purpose of the Study:

  • To investigate whether baicalin (BA) can inhibit Listeria monocytogenes (LM)-induced embryonic loss.
  • To elucidate the molecular mechanisms underlying BA's potential protective effects against LM infection during pregnancy.

Main Methods:

  • In vivo studies involved administering BA to pregnant mice before LM infection and assessing pregnancy outcomes and NLRP3 inflammasome markers.
  • In vitro studies treated macrophages with BA and LM to analyze NLRP3 activation, gasdermin D (GSDMD) cleavage, NEK7-NLRP3 binding, and JNK phosphorylation.
  • Key molecular targets including NLRP3, ASC, caspase-1, GSDMD, IL-1β, NEK7, and JNK were quantified.

Main Results:

  • BA significantly reduced LM-induced embryo loss in mice, correlating with decreased NLRP3, ASC, caspase-1 activation, GSDMD cleavage, IL-1β release, and NEK7-NLRP3 interactions.
  • In vitro, BA suppressed LM-induced NLRP3 inflammasome activation, NEK7-NLRP3 interactions, and JNK phosphorylation in macrophages, while NEK7 expression remained constant.
  • BA's modulation of JNK phosphorylation was found to influence NLRP3 inflammasome-associated protein expression and NEK7-NLRP3 interactions.

Conclusions:

  • The JNK/NEK7-NLRP3/GSDMD signaling pathway is crucial for baicalin's protective effect against Listeria monocytogenes-induced embryonic loss.
  • This study provides a novel mechanistic insight into combating LM-associated infectious diseases during pregnancy.
  • Baicalin emerges as a potential therapeutic agent for preventing embryo loss caused by LM infections.