panduratin-a and Periodontitis

Novel affordable medications are needed to treat chronic periodontitis, which is one of the most common dental pathologies worldwide. Extracts prepared from the rhizome of the medicinal plant Boesenbergia rotunda (L.) Mansf., commonly known as fingerroot, are used to treat a variety of human pathologies. These extracts contain potent anti-inflammatory compounds, including the chalcone derivative panduratin A (Pa-A), which is the lead compound of a series of analogues, designated panduratins A to Y. The anti-inflammatory properties of the extracts of B. rotunda and the most abundant bioactive products found in these extracts (including Pa-A, 4-hydroxyoanduratin, isopanduratin, and others) have been reviewed. A standardized extract of the plant has promising utility in the treatment of gingival inflammation. The effects are characterized by three actions: (i) a direct antimicrobial effect against fungi and oral pathogens such as Porphyromonas gingivalis, (ii) a marked anti-inflammatory effect via a reduced production of mediators, like prostaglandin E2 and different interleukins, and (iii) a dual bone-preserving effect, with a reduction in bone resorption and an increase in bone formation. Acting as a protease inhibitor, Pa-A is one of the main active ingredients of the extract, implicated in these actions. A Pa-A-standardized extract of B. rotunda has been used in humans for treating dyspepsia. The product is safe and well-tolerated. The development of panduratin-containing dental products, for the prevention and treatment of periodontitis, has been proposed. The structural analogues, Pa-A to-Y, should also be investigated for the treatment of dental inflammation.

Topics: Anti-Inflammatory Agents; Chalcone; Chalcones; Humans; Inflammation; Periodontitis; Plant Extracts; Zingiberaceae

Topics: Administration, Oral; Animals; Chalcones; Dogs; Humans; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Periodontitis; Plant Extracts; Rats; Rats, Sprague-Dawley; Zingiberaceae

Periodontitis is an inflammatory disease caused by microbial lipopolysaccharide (LPS), destroying gingival tissues and alveolar bone in the periodontium. In the present study, we evaluated the anti-inflammatory and anti-osteoclastic effects of panduratin A, a chalcone compound isolated from

Topics: Animals; Cathepsin K; Cell Line; Cell Survival; Chalcones; Fibroblasts; Humans; Inflammation; Interleukin-1beta; Lipopolysaccharides; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Matrix Metalloproteinase 8; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; Osteoclasts; Osteogenesis; Periodontitis; Plant Extracts; RANK Ligand; RAW 264.7 Cells; Signal Transduction; Tartrate-Resistant Acid Phosphatase; Transcription Factors; Zingiberaceae

Porphyromonas gingivalis, a type of Gram-negative periodontopathogen, causes periodontal disease by activating intracellular signaling pathways that produce excessive inflammatory responses such as matrix metalloproteinases (MMPs). Recently, we reported that panduratin A, a chalcone compound isolated from Kaempferia pandurata ROXB., caused the decreased levels of MMP-9 secretion, protein, and gene expression in human oral epidermoid KB cells exposed to P. gingivalis supernatant. In this study, we clarified if mitogen-activated protein kinase (MAPK) signaling mediated MMP-9 expression by examining the effect of specific MAPK inhibitors, i.e. U0126, SB203580, and SP600125, on P. gingivalis supernatant-stimulated MMP-9 expression in KB cells. We next elucidated the molecular mechanism by which panduratin A attenuated signaling pathways involved in MMP-9 expression by performing gelatin zymography, Western blotting, reverse transcription-polymerase chain reaction, and promoter assays. Exposure of KB cells to P. gingivalis supernatant up-regulated the expression of MMP-9 protein and gene, and activation of activator protein-1 (AP-1) element, MAPK phosphorylation (extracellular signal-related kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK)), and transcription factors (Elk1, c-Jun, and c-Fos). A JNK inhibitor (SP600125) significantly attenuated MMP-9 gene expression and AP-1 activity in KB cells in response to P. gingivalis supernatant. Similar to SP600125, panduratin A was found to strongly suppress the level of phosphorylated JNK and block AP-1 activity in P. gingivalis supernatant-stimulated KB cells. In summary, JNK and AP-1 are the major signaling for P. gingivalis supernatant-stimulated MMP-9 expression in KB cells, and panduratin A markedly down-regulates MMP-9 expression through inhibition of these signaling.

Topics: Cell Line, Tumor; Chalcones; Epidermal Cells; Epidermis; Gene Expression; Humans; JNK Mitogen-Activated Protein Kinases; KB Cells; MAP Kinase Signaling System; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mitogen-Activated Protein Kinases; Mouth; Periodontitis; Phosphorylation; Plant Extracts; Porphyromonas gingivalis; Protein Kinase Inhibitors; Rhizome; Transcription Factor AP-1; Transcription Factors; Up-Regulation; Zingiberaceae