Effects of Gossypetin from Hibiscus sabdariffa on Interleukin-6 Production in Porphyromonas gingivalis Lipopolysaccharide-Stimulated Human Gingival Fibroblasts
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Background: Periodontal disease is a major cause of tooth loss in adults and is a representative oral disease commonly suffered by most people around the world. Mainly the proliferation of Gram-negative bacteria and secreted virulence factors cause an inflammatory response and destroy periodontal tissue. Gossypetin, isolated from Hibiscus sabdariffa L, is known to have various pharmacological effects, including antibacterial and anticancer activities. We aimed to confirm the anti-inflammatory effect of gossypetin through interleukin-6 (IL-6) regulation in human gingival fibroblasts (HGFs) stimulated with lipopolysaccharide (LPS) of Porphyromonas gingivalis, a major cause of adult periodontitis.Methods: CCK-8 assay was performed to confirm the concentration-dependent cytotoxicity of gossypetin against HGFs. The secretion level and mRNA expression of IL-6, an inflammation-related cytokine, and the effect of gossypetin on these in HGFs stimulated with P. gingivalis LPS were confirmed by ELISA and qRT-PCR analysis, respectively. Results: Up to a concentration of 100 μM gossypetin with or without P. gingivalis LPS, the survival rate for HGFs was maintained at over 95% and showed no toxicity. ELISA and qRT-PCR analysis results showed that P. gingivalis LPS increased IL-6 secretion and mRNA levels in HGFs compared to the control group. However, this increase in IL-6 was significantly down-regulated by gossypetin treatment in a dose-dependent manner. In particular, 80 μM gossypetin inhibited IL-6 production to the level of the control group. Conclusion: These results indicated that gossypetin attenuated IL-6 production in HGFs stimulated by P. gingivalis LPS, which may ultimately suppress the inflammatory response in periodontal tissue. Therefore, gossypetin may have potential as a natural ingredient for the prevention and treatment of periodontal disease.
Abstract
Background: Periodontal disease is a major cause of tooth loss in adults and is a representative oral disease commonly suffered by most people around the world. Mainly the proliferation of Gram-negative bacteria and secreted virulence factors cause an inflammatory response and destroy periodontal tissue. Gossypetin, isolated from Hibiscus sabdariffa L, is known to have various pharmacological effects, including antibacterial and anticancer activities. We aimed to confirm the anti-inflammatory effect of gossypetin through interleukin-6 (IL-6) regulation in human gingival fibroblasts (HGFs) stimulated with lipopolysaccharide (LPS) of Porphyromonas gingivalis, a major cause of adult periodontitis.Methods: CCK-8 assay was performed to confirm the concentration-dependent cytotoxicity of gossypetin against HGFs. The secretion level and mRNA expression of IL-6, an inflammation-related cytokine, and the effect of gossypetin on these in HGFs stimulated with P. gingivalis LPS were confirmed by ELISA and qRT-PCR analysis, respectively. Results: Up to a concentration of 100 μM gossypetin with or without P. gingivalis LPS, the survival rate for HGFs was maintained at over 95% and showed no toxicity. ELISA and qRT-PCR analysis results showed that P. gingivalis LPS increased IL-6 secretion and mRNA levels in HGFs compared to the control group. However, this increase in IL-6 was significantly down-regulated by gossypetin treatment in a dose-dependent manner. In particular, 80 μM gossypetin inhibited IL-6 production to the level of the control group. Conclusion: These results indicated that gossypetin attenuated IL-6 production in HGFs stimulated by P. gingivalis LPS, which may ultimately suppress the inflammatory response in periodontal tissue. Therefore, gossypetin may have potential as a natural ingredient for the prevention and treatment of periodontal disease.
참고문헌 (22)
- Pihlstrom BL, "Periodontal diseases", Lancet, 366, pp.1809~1820 (2005)[DOI]
- Kinane DF, "Periodontal diseases", Nat Rev Dis Primers, 3, pp.17038~ (2017)[DOI]
- Lovegrove JM, "Dental plaque revisited: bacteria associated with periodontal disease", J N Z Soc Periodontol, (87), pp.7~21 (2004)
- Genco RJ, "Risk factors for periodontal disease", Periodontol 2000, 62, pp.59~94 (2013)[DOI]
- How KY, "Porphyromonas gingivalis : an overview of periodontopathic pathogen below the gum line", Front Microbiol, 7, pp.53~ (2016)[DOI]
- Xu W, "Roles of Porphyromonas gingivalis and its virulence factors in periodontitis", Adv Protein Chem Struct Biol, 120, pp.45~84 (2020)[DOI]
- Bozkurt SB, "Porphyromonas gingivalis lipopolysaccharide induces a proinflammatory human gingival fibroblast phenotype", Inflammation, 40, pp.144~153 (2017)[DOI]
- Andrukhov O, "Different effects of P. gingivalis LPS and E. coli LPS on the expression of interleukin-6 in human gingival fibroblasts", Acta Odontol Scand, 72, pp.337~345 (2014)[DOI]
- Liu J, "Beyond toll-like receptors : Porphyromonas gingivalis induces IL-6, IL-8, and VCAM-1expression through NOD-mediated NF-B and ERK signaling pathways in periodontal fibroblasts", Inflammation, 37, pp.522~533 (2014)[DOI]
- Naruishi K, "Biological effects of interleukin-6 on Gingival Fibroblasts : cytokine regulation in periodontitis", J Cell Physiol, 233, pp.6393~6400 (2018)[DOI]
- Xie X, "Gossypetin is a novel MKK3 and MKK6 inhibitor that suppresses esophageal cancer growth in vitro and in vivo", Cancer Lett, 442, pp.126~136 (2019)[DOI]
- Huang K, "Anticancer effects of gossypetin from Hibiscus sabdariffa in oral squamous cell carcinoma", J Appl Oral Sci, 31, pp.e20230243~ (2023)[DOI]
- Diyah NW, "Design of gossypetin derivatives based on naturally occurring flavonoid in Hibiscus sabdariffa and the molecular docking as antibacterial agents", J Basic Clin Physiol Pharmacol, 32, pp.707~714 (2021)[DOI]
- Proença C, "Gossypetin is a novel modulator of inflammatory cytokine production and a suppressor of osteosarcoma cell growth", Antioxidants (Basel), 12, pp.1744~ (2023)[DOI]
- Hoare A, "Chronic inflammation as a link between periodontitis and carcinogenesis", Mediators Inflamm, 2019, pp.1029857~ (2019)[DOI]
- 김아름, "The Interactive Effect of These Bacterial Substrates on the Growth of Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis", 치위생과학회지, 15(2), pp.209~219 (2015), 한국치위생과학회
- Beutler B, "Endotoxin, toll-like receptor 4, and the afferent limb of innate immunity", Curr Opin Microbiol, 3, pp.23~28 (2000)[DOI]
- Herath TD, "Tetra-and penta-acylated lipid A structures of Porphyromonas gingivalis LPS differentially activate TLR4-mediated NF-B signal transduction cascade and immunoinflammatory response in human gingival fibroblasts", PLoS One, 8, pp.e58496~ (2013)[DOI]
- Qiu C, "Lipopolysaccharide preparation derived from Porphyromonas gingivalis induces a weaker immuno-inflammatory response in BV-2 microglial cells than Escherichia coli by differentially activating TLR2", 4-mediated NF-B, Front Cell Infect Microbiol, pp.2021, 11[DOI]
- Winning L, "Periodontitis and systemic disease", BDJ Team, 2, pp.15163~ (2015)[DOI]
- Sawada S, "Enhancement of gingival inflammation induced by synergism of IL-1 and IL-6", Biomed Res, 34, pp.31~40 (2013)[DOI]
- Nakamura A, "Anti-inflammatory effect of lanoconazole on 12-O-tetradecanoylphorbol-13-acetate-and 2, 4, 6-trinitrophenyl chloride-induced skin inflammation in mice", Mycoses, 63, pp.189~196 (2020)[DOI]