Yunvjian decoction attenuates lipopolysaccharide-induced periodontitis by suppressing NFκB/NLRP3/IL-1β pathway

Ethnopharmacological relevance: Yunvjian decoction (YNJ) is a traditional Chinese herbal prescription that has been used in the clinical treatment of periodontitis. However, the underlying molecular mechanism of YNJ in the periodontitis treatment is not well understood. Aim of the study: The purpose of this study was to evaluate the therapeutic effects of YNJ against periodontitis and its underlying molecular mechanisms. Materials and methods: Orthodontic ligation and lipopolysaccharide (LPS)-induced periodontitis rat model was established. YNJ groups were gavaged with YNJ decoction (5 g/kg/d or 10 g/kg/d) for four months. The rats in positive control group were gavaged with metronidazole (MDZ, 100 mg/kg/d) for four months. The maxilla was scanned by micro-computed tomography. The chemical compositions of YNJ were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The molecular mechanism of YNJ were predicted using network pharmacological analysis and validated using immune-staining and Western blot. Results: YNJ treatment decreased the distance between cementoenamel junction and alveolar bone crest on the sagittal slide of the periodontitis rats. Western blot showed YNJ downregulated the protein levels of the bone resorption marker (receptor activator of nuclear factor-kappa B ligand), while upregulated the levels of the bone formation markers (bone morphogenetic protein 2, runt-related transcription factor 2, alkaline phosphatase, and osteoprotegerin) in alveolar bone of the periodontitis rats. Hematoxylin and eosin, immunohistochemical staining, and Western blot analysis indicated that YNJ attenuated the inflammation and decreased the levels of interleukin-6 and tumor necrosis factor-alpha in the alveolar bone. In addition, a total of 61 compounds were identified from YNJ. Network pharmacology indicated that the nucleotide binding oligomerization domain-like receptor signaling pathway was the main pathway for YNJ in the treatment of periodontitis. The experiments confirmed that YNJ administration inhibited LPS induced-pyroptosis in alveolar bone through suppressing the phosphorylation of nuclear factor kappa B, reduced expression of NOD-like receptor family pyrin domain containing 3, and Caspase-1, subsequently suppressing the interleukin-1 beta secretion. Conclusion: YNJ is an effective therapeutic strategy for periodontitis and acts by inhibiting pyroptosis and NF kappa B/ NLRP3/IL-1 beta pathway in alveolar bone.

Automated summary

The study found that Yunvjian decoction (YNJ) has significant therapeutic effects in the treatment of periodontitis. The results showed that YNJ can inhibit bone resorption, promote bone formation, and reduce inflammation in periodontitis rats. Network pharmacology analysis identified the nucleotide binding oligomerization domain-like receptor signaling pathway as the main mechanism of YNJ in treating periodontitis. Additionally, experiments confirmed that YNJ inhibits pyroptosis and suppresses the NF kappa B/NLRP3/IL-1 beta pathway in alveolar bone.