Ginsenoside Compound K Plays an Anti-Inflammatory Role in Gingival Epithelial Cells Stimulated With Porphyromonas...

Globally prevalent periodontitis, an inflammatory disease, may be associated with glucose metabolism disorders. Pyruvate kinase M2 (PKM2), the key enzyme of glycolysis, is potentially implicated in periodontitis pathogenesis, although its precise role is unclear. Ginsenoside compound K (CK) has strong anti-inflammatory effects. Prior studies indicate that CK down-regulates PKM2 expression, yet it remains unclear whether CK can regulate PKM2 to modulate the inflammatory response. Furthermore, CK's role in periodontitis lacks pharmacological investigation.

A periodontitis cell model was established by stimulating human gingival epithelial cells (HGECs) with Porphyromonas gingivalis (Pg), and subsequently intervened with CK. Western blotting assessed the expressions of PKM2, phospho-PKM2 (Tyr105), nuclear factor kappa-B P65 (NF-κB P65), and phosphorylated NF-κB p65 (Ser536). Enzyme-linked immunosorbent assay measured interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in culture supernatants.

Pg stimulation induced NF-κB p65 (Ser536) activation and the secretion of IL-1β and TNF-α in HGECs and promoted PKM2 (Tyr105) phosphorylation. PKM2 was found to be the upstream regulator of NF-κB p65, and NF-κB p65 activated PKM2 through positive feedback to promote IL-1β and TNF-α production, forming a feedback regulatory loop. CK inhibited Pg-induced inflammation and NF-κB p65 (Ser536) and PKM2 (Tyr105) phosphorylation in HGECs. Furthermore, PKM2 overexpression significantly reversed CK's anti-inflammatory effects.

The PKM2/NF-κB p65 pathway is involved in regulating the expression of inflammatory cytokines in Pg-stimulated HGECs and serves as a crucial inflammatory regulatory pathway in the Pg-stimulated HGECs model. CK exhibits anti-inflammatory activity by inhibiting the PKM2-mediated NF-κB signaling pathway and has potential as PKM2 modulator for treating periodontitis and other inflammatory diseases.