Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2012

Open Access 01-12-2012 | Research article

The plant coumarins auraptene and lacinartin as potential multifunctional therapeutic agents for treating periodontal disease

Authors: Annie Marquis, Salvatore Genovese, Francesco Epifano, Daniel Grenier

Published in: BMC Complementary Medicine and Therapies | Issue 1/2012

Login to get access

Abstract

Background

Periodontal diseases are bacterial infections leading to chronic inflammation disorders that are frequently observed in adults. In the present study, we evaluated the effect of auraptene and lacinartin, two natural oxyprenylated coumarins, on the growth, adherence properties, and collagenase activity of Porphyromonas gingivalis. We also investigated the capacity of these compounds to reduce cytokine and matrix metalloproteinase (MMP) secretion by lipopolysaccharide (LPS)-stimulated macrophages and to inhibit MMP-9 activity.

Methods

Microplate dilution assays were performed to determine the effect of auraptene and lacinartin on P. gingivalis growth as well as biofilm formation stained with crystal violet. Adhesion of FITC-labeled P. gingivalis to oral epithelial cells was monitored by fluorometry. The effects of auraptene and lacinartin on LPS-induced cytokine and MMP secretion by macrophages were determined by immunological assays. Fluorogenic assays were used to evaluate the capacity of the two coumarins to inhibit the activity of P. gingivalis collagenase and MMP-9.

Results

Only lacinartin completely inhibited P. gingivalis growth in a complex culture medium. However, under iron-limiting conditions, auraptene and lacinartin both inhibited the growth of P. gingivalis. Lacinartin also inhibited biofilm formation by P. gingivalis and promoted biofilm desorption. Both compounds prevented the adherence of P. gingivalis to oral epithelial cells, dose-dependently reduced the secretion of cytokines (IL-8 and TNF-α) and MMP-8 and MMP-9 by LPS-stimulated macrophages, and inhibited MMP-9 activity. Lacinartin also inhibited P. gingivalis collagenase activity.

Conclusions

By acting on multiple targets, including pathogenic bacteria, tissue-destructive enzymes, and the host inflammatory response, auraptene and lacinartin may be promising natural compounds for preventing and treating periodontal diseases.
Appendix
Available only for authorised users
Literature
1.
go back to reference Highfield J: Diagnosis and classification of periodontal disease. Aust Dent J. 2009, 54 (Suppl 1): S11-26.CrossRefPubMed Highfield J: Diagnosis and classification of periodontal disease. Aust Dent J. 2009, 54 (Suppl 1): S11-26.CrossRefPubMed
2.
go back to reference Burt B: Position paper: epidemiology of periodontal diseases. J Periodontol. 2005, 76 (8): 1406-1419.CrossRefPubMed Burt B: Position paper: epidemiology of periodontal diseases. J Periodontol. 2005, 76 (8): 1406-1419.CrossRefPubMed
3.
go back to reference Feng Z, Weinberg A: Role of bacteria in health and disease of periodontal tissues. Periodontol 2000. 2006, 40: 50-76. 10.1111/j.1600-0757.2005.00148.x.CrossRefPubMed Feng Z, Weinberg A: Role of bacteria in health and disease of periodontal tissues. Periodontol 2000. 2006, 40: 50-76. 10.1111/j.1600-0757.2005.00148.x.CrossRefPubMed
4.
go back to reference Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE: Defining the normal bacterial flora of the oral cavity. J Clin Microbiol. 2005, 43 (11): 5721-5732. 10.1128/JCM.43.11.5721-5732.2005.CrossRefPubMedPubMedCentral Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE: Defining the normal bacterial flora of the oral cavity. J Clin Microbiol. 2005, 43 (11): 5721-5732. 10.1128/JCM.43.11.5721-5732.2005.CrossRefPubMedPubMedCentral
5.
go back to reference Holt SC, Ebersole JL: Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the "red complex", a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000. 2005, 38: 72-122. 10.1111/j.1600-0757.2005.00113.x.CrossRefPubMed Holt SC, Ebersole JL: Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the "red complex", a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000. 2005, 38: 72-122. 10.1111/j.1600-0757.2005.00113.x.CrossRefPubMed
6.
go back to reference Garlet GP: Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 2010, 89 (12): 1349-1363. 10.1177/0022034510376402.CrossRefPubMed Garlet GP: Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 2010, 89 (12): 1349-1363. 10.1177/0022034510376402.CrossRefPubMed
7.
go back to reference Kornman KS, Page RC, Tonetti MS: The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000. 1997, 14: 33-53. 10.1111/j.1600-0757.1997.tb00191.x.CrossRefPubMed Kornman KS, Page RC, Tonetti MS: The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000. 1997, 14: 33-53. 10.1111/j.1600-0757.1997.tb00191.x.CrossRefPubMed
8.
go back to reference Pandey KB, Rizvi SI: Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009, 2 (5): 270-278. 10.4161/oxim.2.5.9498.CrossRefPubMedPubMedCentral Pandey KB, Rizvi SI: Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009, 2 (5): 270-278. 10.4161/oxim.2.5.9498.CrossRefPubMedPubMedCentral
9.
go back to reference Scalbert A, Johnson IT, Saltmarsh M: Polyphenols: antioxidants and beyond. Am J Clin Nutr. 2005, 81 (1 Suppl): 215S-217S.PubMed Scalbert A, Johnson IT, Saltmarsh M: Polyphenols: antioxidants and beyond. Am J Clin Nutr. 2005, 81 (1 Suppl): 215S-217S.PubMed
10.
go back to reference El Gharras H: Polyphenols: food sources, properties and applications – a review. Int J Food Sci Technol. 2009, 44 (12): 2512-2518. 10.1111/j.1365-2621.2009.02077.x.CrossRef El Gharras H: Polyphenols: food sources, properties and applications – a review. Int J Food Sci Technol. 2009, 44 (12): 2512-2518. 10.1111/j.1365-2621.2009.02077.x.CrossRef
11.
go back to reference Bravo L: Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev. 1998, 56 (11): 317-333.CrossRefPubMed Bravo L: Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev. 1998, 56 (11): 317-333.CrossRefPubMed
12.
go back to reference Cos P, De Bruyne T, Hermans N, Apers S, Berghe DV, Vlietinck AJ: Proanthocyanidins in health care: current and new trends. Curr Med Chem. 2004, 11 (10): 1345-1359.CrossRefPubMed Cos P, De Bruyne T, Hermans N, Apers S, Berghe DV, Vlietinck AJ: Proanthocyanidins in health care: current and new trends. Curr Med Chem. 2004, 11 (10): 1345-1359.CrossRefPubMed
13.
go back to reference Genovese S, Epifano F: Auraptene: a natural biologically active compound with multiple targets. Curr Drug Targets. 2011, 12 (3): 381-386.CrossRefPubMed Genovese S, Epifano F: Auraptene: a natural biologically active compound with multiple targets. Curr Drug Targets. 2011, 12 (3): 381-386.CrossRefPubMed
14.
go back to reference Borges F, Roleira F, Milhazes N, Santana L, Uriarte E: Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity. Curr Med Chem. 2005, 12 (8): 887-916. 10.2174/0929867053507315.CrossRefPubMed Borges F, Roleira F, Milhazes N, Santana L, Uriarte E: Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity. Curr Med Chem. 2005, 12 (8): 887-916. 10.2174/0929867053507315.CrossRefPubMed
15.
go back to reference Komatsu S, Tanaka S, Ozawa S, Kubo R, Ono Y, Matsuda Z: Biochemical studies on grape fruits, Citrus aurantium. Nippon Kagaku Kaishi. 1930, 51: 478-498. 10.1246/nikkashi1921.51.478.CrossRef Komatsu S, Tanaka S, Ozawa S, Kubo R, Ono Y, Matsuda Z: Biochemical studies on grape fruits, Citrus aurantium. Nippon Kagaku Kaishi. 1930, 51: 478-498. 10.1246/nikkashi1921.51.478.CrossRef
16.
go back to reference Nagao K, Yamano N, Shirouchi B, Inoue N, Murakami S, Sasaki T, Yanagita T: Effects of citrus auraptene (7-geranyloxycoumarin) on hepatic lipid metabolism in vitro and in vivo. J Agric Food Chem. 2010, 58 (16): 9028-9032. 10.1021/jf1020329.CrossRefPubMed Nagao K, Yamano N, Shirouchi B, Inoue N, Murakami S, Sasaki T, Yanagita T: Effects of citrus auraptene (7-geranyloxycoumarin) on hepatic lipid metabolism in vitro and in vivo. J Agric Food Chem. 2010, 58 (16): 9028-9032. 10.1021/jf1020329.CrossRefPubMed
17.
go back to reference Ogawa K, Kawasaki A, Yoshida T, Nesumi H, Nakano M, Ikoma Y, Yano M: Evaluation of auraptene content in citrus fruits and their products. J Agric Food Chem. 2000, 48 (5): 1763-1769. 10.1021/jf9905525.CrossRefPubMed Ogawa K, Kawasaki A, Yoshida T, Nesumi H, Nakano M, Ikoma Y, Yano M: Evaluation of auraptene content in citrus fruits and their products. J Agric Food Chem. 2000, 48 (5): 1763-1769. 10.1021/jf9905525.CrossRefPubMed
18.
go back to reference Epifano F, Genovese S, Curini M: Auraptene: Phytochemical and pharmacological properties. Phytochemistry Research Progress. Edited by: Matsumoto T. 2008, Nova Science Publishers Inc, Hauppaughe,NY (USA), 145-162. Epifano F, Genovese S, Curini M: Auraptene: Phytochemical and pharmacological properties. Phytochemistry Research Progress. Edited by: Matsumoto T. 2008, Nova Science Publishers Inc, Hauppaughe,NY (USA), 145-162.
19.
go back to reference Tanaka T, Kawabata K, Kakumoto M, Matsunaga K, Mori H, Murakami A, Kuki W, Takahashi Y, Yonei H, Satoh K: Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by citrus auraptene in rats. Carcinogenesis. 1998, 19 (3): 425-431. 10.1093/carcin/19.3.425.CrossRefPubMed Tanaka T, Kawabata K, Kakumoto M, Matsunaga K, Mori H, Murakami A, Kuki W, Takahashi Y, Yonei H, Satoh K: Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by citrus auraptene in rats. Carcinogenesis. 1998, 19 (3): 425-431. 10.1093/carcin/19.3.425.CrossRefPubMed
20.
go back to reference Genovese S, Epifano F, Curini M, Dudra-Jastrzebska M, Luszczki JJ: Prenyloxyphenylpropanoids as a novel class of anticonvulsive agents. Bioorg Med Chem Lett. 2009, 19 (18): 5419-5422. 10.1016/j.bmcl.2009.07.110.CrossRefPubMed Genovese S, Epifano F, Curini M, Dudra-Jastrzebska M, Luszczki JJ: Prenyloxyphenylpropanoids as a novel class of anticonvulsive agents. Bioorg Med Chem Lett. 2009, 19 (18): 5419-5422. 10.1016/j.bmcl.2009.07.110.CrossRefPubMed
21.
go back to reference Darveau RP, Hancock RE: Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains. J Bacteriol. 1983, 155 (2): 831-838.PubMedPubMedCentral Darveau RP, Hancock RE: Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains. J Bacteriol. 1983, 155 (2): 831-838.PubMedPubMedCentral
22.
go back to reference Darveau RP: Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol. 2010, 8 (7): 481-490. 10.1038/nrmicro2337.CrossRefPubMed Darveau RP: Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol. 2010, 8 (7): 481-490. 10.1038/nrmicro2337.CrossRefPubMed
23.
go back to reference Pihlstrom BL, Michalowicz BS, Johnson NW: Periodontal diseases. Lancet. 2005, 366 (9499): 1809-1820. 10.1016/S0140-6736(05)67728-8.CrossRefPubMed Pihlstrom BL, Michalowicz BS, Johnson NW: Periodontal diseases. Lancet. 2005, 366 (9499): 1809-1820. 10.1016/S0140-6736(05)67728-8.CrossRefPubMed
24.
go back to reference Epifano F, Menghini L, Pagiotti R, Angelini P, Genovese S, Curini M: In vitro inhibitory activity of boropinic acid against Helicobacter pylori. Bioorg Med Chem Lett. 2006, 16 (21): 5523-5525. 10.1016/j.bmcl.2006.08.043.CrossRefPubMed Epifano F, Menghini L, Pagiotti R, Angelini P, Genovese S, Curini M: In vitro inhibitory activity of boropinic acid against Helicobacter pylori. Bioorg Med Chem Lett. 2006, 16 (21): 5523-5525. 10.1016/j.bmcl.2006.08.043.CrossRefPubMed
25.
go back to reference Takeda K, Utsunomiya H, Kakiuchi S, Okuno Y, Oda K, Inada K, Tsutsumi Y, Tanaka T, Kakudo K: Citrus auraptene reduces Helicobacter pylori colonization of glandular stomach lesions in Mongolian gerbils. J Oleo Sci. 2007, 56 (5): 253-260. 10.5650/jos.56.253.CrossRefPubMed Takeda K, Utsunomiya H, Kakiuchi S, Okuno Y, Oda K, Inada K, Tsutsumi Y, Tanaka T, Kakudo K: Citrus auraptene reduces Helicobacter pylori colonization of glandular stomach lesions in Mongolian gerbils. J Oleo Sci. 2007, 56 (5): 253-260. 10.5650/jos.56.253.CrossRefPubMed
26.
go back to reference Wu L, Wang X, Xu W, Farzaneh F, Xu R: The structure and pharmacological functions of coumarins and their derivatives. Curr Med Chem. 2009, 16 (32): 4236-4260. 10.2174/092986709789578187.CrossRefPubMed Wu L, Wang X, Xu W, Farzaneh F, Xu R: The structure and pharmacological functions of coumarins and their derivatives. Curr Med Chem. 2009, 16 (32): 4236-4260. 10.2174/092986709789578187.CrossRefPubMed
27.
go back to reference Mladenka P, Macakova K, Zatloukalova L, Rehakova Z, Singh BK, Prasad AK, Parmar VS, Jahodar L, Hrdina R, Saso L: In vitro interactions of coumarins with iron. Biochimie. 2010, 92 (9): 1108-1114. 10.1016/j.biochi.2010.03.025.CrossRefPubMed Mladenka P, Macakova K, Zatloukalova L, Rehakova Z, Singh BK, Prasad AK, Parmar VS, Jahodar L, Hrdina R, Saso L: In vitro interactions of coumarins with iron. Biochimie. 2010, 92 (9): 1108-1114. 10.1016/j.biochi.2010.03.025.CrossRefPubMed
28.
go back to reference Andrian E, Grenier D, Rouabhia M: Porphyromonas gingivalis-epithelial cell interactions in periodontitis. J Dent Res. 2006, 85 (5): 392-403. 10.1177/154405910608500502.CrossRefPubMed Andrian E, Grenier D, Rouabhia M: Porphyromonas gingivalis-epithelial cell interactions in periodontitis. J Dent Res. 2006, 85 (5): 392-403. 10.1177/154405910608500502.CrossRefPubMed
29.
go back to reference Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA: Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001, 74 (4): 418-425.PubMed Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA: Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001, 74 (4): 418-425.PubMed
30.
go back to reference Genovese S, Curini M, Epifano F: Prenyloxyphenylpropanoids as a novel class of anti-inflammatory agents. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry. 2010, 9 (2): 158-165.CrossRef Genovese S, Curini M, Epifano F: Prenyloxyphenylpropanoids as a novel class of anti-inflammatory agents. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry. 2010, 9 (2): 158-165.CrossRef
31.
go back to reference Okada H, Murakami S: Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med. 1998, 9 (3): 248-266. 10.1177/10454411980090030101.CrossRefPubMed Okada H, Murakami S: Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med. 1998, 9 (3): 248-266. 10.1177/10454411980090030101.CrossRefPubMed
32.
go back to reference Kawabata K, Murakami A, Ohigashi H: Auraptene decreases the activity of matrix metalloproteinases in dextran sulfate sodium-induced ulcerative colitis in ICR mice. Biosci Biotechnol Biochem. 2006, 70 (12): 3062-3065. 10.1271/bbb.60393.CrossRefPubMed Kawabata K, Murakami A, Ohigashi H: Auraptene decreases the activity of matrix metalloproteinases in dextran sulfate sodium-induced ulcerative colitis in ICR mice. Biosci Biotechnol Biochem. 2006, 70 (12): 3062-3065. 10.1271/bbb.60393.CrossRefPubMed
Metadata
Title
The plant coumarins auraptene and lacinartin as potential multifunctional therapeutic agents for treating periodontal disease
Authors
Annie Marquis
Salvatore Genovese
Francesco Epifano
Daniel Grenier
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2012
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-12-80

Other articles of this Issue 1/2012

BMC Complementary Medicine and Therapies 1/2012 Go to the issue