The TLR4-NLRP3 signaling pathway plays an essential role in the development of inflammation and especially endometritis. Rosmarinic acid (RA) can have potent anti-inflammatory effects in the drug-loading system. The purpose of this was to evaluate the anti-inflammatory effects of RA loaded to exosomes (RLE) on lipopolysaccharide (LPS)-induced endometritis in mice. RA was loaded into serum-derived exosome, using sonication methods. Animals in the treatment groups were subjected to uterine horn injection of RA, exosome, RA combination with exosome (R+E), and RA loaded to exosome (RLE) in uterine horn by two dosages in each group (5 and 10 mg/kg of RA or exosome), 24 h after inducing endometritis. Histopathological analysis, MPO production, immunohistochemistry, and qPCR were used to determine whether the treatment groups were adequate in controlling inflammation. The results showed that treatment groups, and mainly RLE10 and R10 +E10 groups, could modulate pathological changes, inhibit myeloperoxidase (MPO) activity, and significantly reduce the gene and protein expression of TLR4, NLRP3, inflammatory cytokines such as IL-1β, IL-18, and TNF-α, and lastly, GSDM-D as a pyroptosis factor. In conclusion, RA loaded and combination with exosomes at a dosage of 10 mg/kg (RLE10 and R10 +E10) improved endometritis in mice through a suppressing TLR4-NLRP3 signaling pathway.
Keywords: Endometritis; Immunohistochemistry; NLRP3; Rosmarinic acid; Sonication.
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