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

  • Int Immunopharmacol. 2026 Jan 1;168(Pt 2):115921. doi: 10.1016/j.intimp.2025.115921.
Enhua Zhang  1 ,  Jing Chen  1 ,  Wen Liu  1 ,  Tingting Cai  2 ,  Siyun Niu  3 ,  Zheng Gao  4 ,  Wenyan Li  5
Affiliations
  • 1. School of Basic Medical Sciences, Hebei University, Baoding 071001, China.
  • 2. Department of Clinical Laboratory, Affiliated Hospital of Hebei University, Baoding 071001, China.
  • 3. School of Basic Medical Sciences, Hebei University, Baoding 071001, China. Electronic address: [email protected].
  • 4. School of Basic Medical Sciences, Hebei University, Baoding 071001, China. Electronic address: [email protected].
  • 5. School of Basic Medical Sciences, Hebei University, Baoding 071001, China. Electronic address: [email protected].
PMID: 41289943 DOI: 10.1016/j.intimp.2025.115921
Abstract

Background: Listeria monocytogenes (LM) infections can cause embryo loss by activating the NOD-like Receptor thermal protein domain associated protein 3 (NLRP3) inflammasome at the maternal-fetal interface. Baicalin (BA), the primary active component of Scutellaria baicalensis, has been confirmed to play a critical role in fetal preservation. Nevertheless, whether BA can inhibit LM-induced embryonic loss and the potential molecular mechanism remain elusive.

Methods: In vivo, pregnant BALB/c mice were administered with BA on gestational day (GD) 0.5 for 6 consecutive days and infected with LM on GD 6.5. Pregnancy outcomes were analyzed and NLRP3 inflammasome-associated protein and Pyroptosis related indexes were measured on GD 9.5. In vitro, macrophages were treated with BA and (or) LM. NLRP3 activation, gasdermin D (GSDMD) cleavage, NIMA-related kinase 7 (NEK7)-NLRP3 binding and JNK phosphorylation were tested in cells.

Results: BA significantly reduced LM-induced mouse embryo loss, accompanied by the decrease of NLRP3 and ASC protein expression, Caspase-1 activation, GSDMD cleavage, IL-1β release and NEK7-NLRP3 interactions in uteri. In vitro experiments showed that BA alleviated LM-induced NLRP3 inflammasome-associated protein expressions, NEK7-NLRP3 interactions and JNK phosphorylation in macrophages. Interestingly, NEK7 expression levels remained unchanged in all experimental groups. Additionally, BA-mediated modulation of JNK phosphorylation could alter the expression of NLRP3 inflammasome-associated proteins and NEK7-NLRP3 interactions.

Conclusion: Our data indicated that JNK/NEK7-NLRP3/GSDMD signaling pathway plays a key role in BA-mediated alleviation of LM-induced embryonic loss, which provided a novel perspective for combating LM-associated infectious diseases.

Keywords
Baicalin; Embryonic loss; JNK; Listeria monocytogenes; NEK7; NLRP3 inflammasome.
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