Dual antibiofilm and antimetalloproteinase-9 activities of panduratin A in experimental periodontal disease models: A potent natural periodontotherapeutic

Abstract

We examined the efficacy of panduratin A, a chalcone compound isolated from Kaempferia pandurata Roxb., on inhibition of oral biofilms and MMP expression by conducting experimental periodontal disease models in vitro and in vivo. Oral biofilms were formed by multi-species oral colonizers, including Streptococcus mutans, S. sanguis, and Actinomyces viscosus. Human gingival fibroblasts and oral epithelial cells induced by Porphyromonas gingivalis were employed as the in vitro oral culture models for the expression of MMPs and their signaling pathways. The effect of panduratin A on attenuating the expression of MMP-dependent gingival inflammation was also evaluated by conducting in vivo test using lipopolysaccharide (LPS)-induced rat gingiva. Our findings suggest that panduratin A possesses anti-biofilm activity by eliminating oral bacterial colonization during early dental plaque formation. Panduratin A may control periodontal inflammation involving MMP-2 and MMP-9 induction in human gingival fibroblasts and oral epithelial cells in vitro. In oral epithelial cells, panduratin A decreases MMP-9 gene expression by suppressing P. gingivalis supernatant-stimulated AP-1 activation which may be mediated by blocking ERK1/2 and JNK phosphorylation. Meanwhile, in gingival fibroblasts, panduratin A inhibits P. gingivalis supernatant-stimulated MMP-2 gene expression through down-regulating CREB signaling that may be facilitated by attenuation of p38 phosphorylation. Panduratin A also attenuates the expression of MMP-9 secretion, protein, and mRNA in LPS-induced rat gingival inflammation in vivo, thus subsequently resulting in the improvement of the gingival tissue morphology. With dual potent activities as antibiofilm and anti-MMP-9 agent, panduratin A could be applied as a promising candidate in periodontotherapy.