FuKe QianJin capsule alleviates endometritis via inhibiting inflammation and pyroptosis through modulating TLR4/ NF-κB /NLRP3 pathway.

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    • Source:
      Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: Limerick : Elsevier Sequoia
      Original Publication: Lausanne, Elsevier Sequoia.
    • Subject Terms:
    • Abstract:
      Ethnopharmacological Relevance: Fuke Qianjin Capsule (FKC), a traditional Chinese medicine commonly employed for treating endometritis, lacks reported treatment mechanisms.
      Aim of the Study: The aim of the present study was to explore the role and mechanism of FKC in lipopolysaccharide (LPS)-induced endometritis.
      Materials and Methods: The main active ingredients of FKC were identified via high-performance liquid chromatography (HPLC) in conjunction with standard substances. Prior to endometritis induction, Sprague Dawley female rats received FKC for 7 days. The endometritis model was established through an intrauterine injection of 1 mg/kg LPS. Concurrently, an LPS-induced RAW264.7 cell inflammation model was utilized, in which the cells were treated with serum containing Fuke Qianjin Capsule. Pathological alterations in the endometrium were assessed via H&E staining and transmission electron microscopy (TEM). The contents of MPO in uterine tissues, and NO release in cells, along with the secretion of IL-18, IL-1β, IL-6, and TNF-α in both tissues and cells, were determined via assay kits. The mRNA levels of Nlrp3, Caspase-1, Gsdmd, and Il-1β in uterine tissues and cells were analyzed via qPCR. The protein levels of TLR4, p65, p-P65, NLRP3, Caspase-1, GSDMD, and IL-1β in these samples were evaluated through Western blot analysis. Immunofluorescence was used to assess the protein levels of p-P65 and NLRP3 in uterine tissues and cells.
      Results: Five primary active components of FKC were identified. Treatment with FKC in vivo mitigated endometrial pathological damage and significantly decreased the levels of MPO, IL-18, IL-1β, IL-6, and TNF-α, as well as the levels of Nlrp3, Caspase-1, Gsdmd, and Il-1β mRNA in tissue samples. Treatment with FKC inhibited the expression of TLR4, p-P65, NLRP3, Caspase-1, GSDMD, and IL-1β, as well as reduced NLRP3 protein fluorescence intensity, and inhibited P65 phosphorylation. In vitro findings demonstrated that FKC-containing serum reduced IL-18, IL-1β, IL-6, and TNF-α levels, as well as reduced Nlrp3, Caspase-1, Gsdmd, and Il-1β mRNA levels. In addition, FKC-containing serum inhibited the protein expression of TLR4, p-P65, NLRP3, Caspase-1, GSDMD, and IL-1β. FKC-containing serum also reduced NLRP3 protein fluorescence intensity and suppressed P65 phosphorylation.
      Conclusion: FKC reverses the LPS induced NLRP3 inflammasome activation, and mitigates inflammation and pyroptosis through the modulation of the TLR4/NF-κB/NLRP3 pathway, thereby alleviating endometritis.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Endometritis; FuKe QianJin capsule; LPS; NLRP3; Pyroptosis
    • Accession Number:
      0 (NLR Family, Pyrin Domain-Containing 3 Protein)
      0 (Toll-Like Receptor 4)
      0 (Drugs, Chinese Herbal)
      0 (Tlr4 protein, rat)
      0 (Nlrp3 protein, rat)
      0 (NF-kappa B)
      0 (Lipopolysaccharides)
      0 (Anti-Inflammatory Agents)
    • Publication Date:
      Date Created: 20241019 Date Completed: 20241113 Latest Revision: 20241113
    • Publication Date:
      20241114
    • Accession Number:
      10.1016/j.jep.2024.118962
    • Accession Number:
      39426577