Betulin inhibits the production of inflammatory cytokines in human gingival fibroblasts and ligature-induced periodontitis

Chronic inflammation of the tissues surrounding and supporting the teeth is known as periodontal disease. Human gingival fibroblasts (HGFs) are among the greatest prevalent cells in gingival tissue and play a crucial role in oral infections. Data from the GSE dataset revealed that the inflammatory cytokines IL-1β, IL-6, and IL-8 were up-regulated in periodontitis patients compared to healthy individuals. Betulin, a lupane-type pentacyclic triterpene alcohol extracted from the birch trees, inhibits lipopolysaccharide (LPS; component of gram-negative bacteria)-induced synthesis of IL-1β, IL-6, and IL-8 in HGFs. We also demonstrated that the MAPK and AP-1 signaling cascades mediate betulin's inhibition of inflammatory cytokine production in HGFs. Importantly, betulin reduces the expression of inflammatory cytokines and prevents the progression of ligature-induced periodontitis in vivo. This study provides evidence that betulin is a promising candidate for the management of periodontal disease.