Abstract
Periodontitis is a set of chronic inflammatory diseases caused by the accumulation of Gram-negative bacteria on teeth, resulting in gingivitis, pocket formation, alveolar bone loss, tissue destruction, and tooth loss. In this study, the contents of ginsenosides isolated from Panax ginseng fruit extract were quantitatively analyzed, and the anti-inflammatory effects were evaluated in human periodontal ligament cells. The major ginsenosides, Re, Ra8, and Rf, present in ginseng fruit were simultaneously analyzed by a validated method using high-performance liquid chromatography with a diode-array detector; Re, Ra8, and Rf content per 1 g of P. ginseng fruit extract was 1.01 ± 0.03, 0.33 ± 0.01, and 0.55 ± 0.04 mg, respectively. Ginsenosides-Re, -Ra8, and -Rf inhibited the production of pro-inflammatory factors and the expression of important cytokines in periodontitis by inducing the expression of heme oxygenase 1 (HO-1), promoting osteoblast differentiation of periodontal ligament cells, suppressing alveolar bone loss, and promoting the expression of osteoblast-specific genes, such as alp, opn, and runx2. An inhibitory effect of these ginsenosides on periodontitis and alveolar bone loss was observed via the regulation of HO-1 and subsequent epidermal growth factor receptor (EGFR) signaling. Silencing EGFR with EGFR siRNA confirmed that the effect of ginsenosides on HO-1 is mediated by EGFR. In conclusion, this study evaluated the contents of ginsenosides-Re, -Ra8, and -Rf isolated from P. ginseng fruit extract. Therefore, these results provide important basic data for future P. ginseng fruit component studies and suggest that ginsenosides Re, Ra8, and Rf have potential as future treatment options for periodontitis.
Highlights
Periodontitis is a multifactorial chronic disease caused by the accumulation of Gramnegative bacteria on teeth [1] that usually occurs in early adulthood but can start in childhood or adolescence [2]
To investigate the role of epidermal growth factor receptor (EGFR) signaling in the regulation of heme oxygenase 1 (HO-1) expression, we examined whether EGFR is regulated by ginsenosides
In addition to the anti-inflammatory effect of ginsenosides via the regulation of HO-1 expression in Porphyromonas gingivalis (PG)-LPS-stimulated human periodontal ligament (HPDL) cells, we evaluated the effect of ginsenosideinduced HO-1 expression on other important treatment strategies for periodontitis such as the inhibition of alveolar bone loss
Summary
Periodontitis is a multifactorial chronic disease caused by the accumulation of Gramnegative bacteria on teeth [1] that usually occurs in early adulthood but can start in childhood or adolescence [2]. The structure of Gram-negative bacteria is different from that of other bacteria and is surrounded by two cell membranes with a thin layer of peptidoglycan bonded between them [5]. These Gram-negative bacteria are involved in several stages such as inflammation and alveolar bone loss due to the fact of periodontitis, tooth loss, and periodontal tissue destruction. The model for induction of periodontitis using Porphyromonas gingivalis (PG)lipopolysaccharide (LPS) belonging to Gram-negative bacteria is known as a representative model in typical experimental periodontitis studies [6]
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