Inhibitory Effects of Panduratin A on Periodontitis-Induced Inflammation and Osteoclastogenesis through Inhibition of MAPK Pathways In Vitro

Abstract

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 , in human gingival fibroblast-1 (HGF-1) and RAW 264.7 cells. Treatment of panduratin A to LPS-stimulated HGF-1 significantly reduced the expression of interleukin-1β and nuclear factor-kappa B (NF-κB), subsequently leading to the inhibition of matrix metalloproteinase-2 (MMP-2) and MMP-8 compared with that in the LPS control (** < 0.01). These anti-inflammatory responses were mediated by suppressing the mitogen-activated protein kinase (MAPK) signaling and activator protein-1 complex formation pathways. Moreover, receptor activator of NF-κB ligand (RANKL)-stimulated RAW 264.7 cells treated with panduratin A showed significant inhibition of osteoclastic transcription factors such as nuclear factor of activated T-cells c1 and c-Fos as well as osteoclastic enzymes such as tartrate-resistant acid phosphatase and cathepsin K compared with those in the RANKL control (** < 0.01). Similar to HGF-1, panduratin A suppressed osteoclastogenesis by controlling MAPK signaling pathways. Taken together, these results suggest that panduratin A could be a potential candidate for development as a natural anti-periodontitis agent.

4-Hydroxypanduratin A and Isopanduratin A Inhibit Tumor Necrosis Factor α-Stimulated Gene Expression and the Nuclear Factor κB-Dependent Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

“…Panduratin A and its derivatives have been shown to exhibit anti-tumor activity toward a number of cancer cell lines. 10,11,13,14,28,29) In contrast, panduratin A, 4-hydroxypanduratin A, and isopanduratin A inhibited TNF-α plus actinomycin D-induced cell death in L929 cells. 30) Panduratin A and 4-hydroxypanduratin A have also been shown to reduce L-glutamate toxicity in N18-RE-105 cells.…”

“…Panduratin A has been shown to inhibit LPS-induced IκBα phosphorylation and its degradation in RAW264.7 cells, 12) as well as the TNF-α-stimulated translocation of p65 and p50 to the nucleus in A549 cells. 13,14) A previous study reported that panduratin A reduced the expression of NF-κB in LPS-stimulated gingival fibroblast-1 cells. 15) Collectively, these findings indicated that panduratin A inhibited the NF-κB signaling pathway.…”

“…10) Previous studies demonstrated that panduratin A inhibited the NF-κB signaling pathway in the murine monocyte cell line RAW264.7 and human lung adenocarcinoma A549 cells. [12][13][14] The expression of NF-κB was reduced by panduratin A in lipopolysaccharide (LPS)-induced human gingival fibroblast-1 cells. 15) However, in contrast to panduratin A, the biological activities of 4-hydroxypanduratin A and isopanduratin A on the NF-κB signaling pathway remain unclear.…”

Inhibitory Effects of Curcuma xanthorrhiza Supercritical Extract and Xanthorrhizol on LPS-Induced Inflammation in HGF-1 Cells and RANKL-Induced Osteoclastogenesis in RAW264.7 Cells

“…To assess the anti-osteoclastic activities of CXS and XAN, we used RAW264.7 cells with RANKL as an osteoclastogenesis inducer [5]. RANKL treatment elevated both the protein and mRNA levels of the osteoclastic transcription factors and bone degradation enzymes, NFATc1, c-Fos, cathepsin K, and TRAP, whereas CXS and XAN treatments decreased the expression levels (Figs.…”

“…The interaction between LPS and TLR activates the nuclear factor kappa B (NF-κB) or mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathway [4]. The NF-κB and MAPK/AP-1 pathways subsequently upregulate interleukin (IL)-1β, a major cytokine, and matrix metalloproteinases (MMPs), which are protein degradation enzymes, consequently destroying the periodontal ligament [4,5].…”