Citrus Auraptene Reduces Helicobacter pylori Colonization of Glandular Stomach Lesions in Mongolian Gerbils

Takeda, Koichi; Utsunomiya, Hirotoshi; Kakiuchi, Seiji; Okuno, Yoshiharu; Oda, Koji; Inada, Ken Ichi; Tsutsumi, Yutaka; Tanaka, Takuji; Kakudo, Kennichi

doi:10.5650/jos.56.253

Cited by 23 publications

(20 citation statements)

References 30 publications

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“…This is the first report indicating that lacinartin possesses anti-bacterial properties. Previous studies have shown that auraptene has antibacterial properties against Helicobacter pylori [24,25] . The exact mechanism by which lacinartin and auraptene inhibit bacterial growth is unknown.…”

Section: Discussionmentioning

confidence: 99%

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

Marquis

Genovese

Epifano

et al. 2012

BMC Complement Altern Med

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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.

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Section: Discussionmentioning

confidence: 99%

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

Marquis

Genovese

Epifano

et al. 2012

BMC Complement Altern Med

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“…3c). 12) Auraptene (1) is a major coumarin in Citrus plants, and numerous studies have demonstrated 1 to have various biological functions in the peripheral tissues, including anti-inflammatory activity, 13,14) anti-carcinogenic activity, 15,16) anti-Helicobacter activity, 17) and regulatory activity toward hepatic lipid metabolism. 18,19) It has also recently been reported that 1 had the ability to promote neurite outgrowth from PC12 cells.…”

mentioning

confidence: 99%

Characterization of Constituents in the Peel ofCitrus kawachiensis(Kawachibankan)

Amakura

Yoshimura

Ouchi

et al. 2013

Bioscience, Biotechnology, and Biochemistry

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“…21) Takeda et al have recently shown that auraptene exhibited anti-H. pylori colonization activity in Mongolian gerbils. 22) In this present study, auraptene inhibited H. pylori adhesion to NCI-N87 cells by only 27% (Fig. 2A).…”

Section: Discussionmentioning

confidence: 39%

“…21) Interestingly, Takeda et al have indicated that an oral administration of auraptene inhibited H. pylori colonization in Mongolian gerbils. 22) However, this study did not clarify its mechanisms of action. We thus attempted in this present study to elucidate the molecular mechanism by which auraptene suppresses CD74 in NCI-N87 human gastric carcinoma cells.…”

mentioning

confidence: 96%

Suppression of CD74 Expression andHelicobacter pyloriAdhesion by Auraptene Targeting Serum Starvation-Activated ERK1/2 in NCI-N87 Gastric Carcinoma Cells

Sekiguchi¹,

Irie²,

Murakami³

2010

Bioscience, Biotechnology, and Biochemistry

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Helicobacter pylori (H. pylori) is a major human pathogen and plays a central role in chronic gastritis and gastric cancer. Since the adhesion of H. pylori to the human gastric epithelium is the initial and critical step of its infection, anti-H. pylori adhesion agents may be effective for the prevention and therapy of H. pylori-associated diseases. CD74 has recently been identified as a new receptor for H. pylori urease, and we have previously reported that several citrus components strongly suppressed CD74 expression in NCI-N87 gastric carcinoma cells. We found in this present study that auraptene (citrus coumarin) disrupted serum starvation-induced extracellular signaling-regulated kinase (ERK) 1/2 activation and attenuated H. pylori adhesion and IL-8 production in a co-culture system. In addition, the knockdown of CD74 expression led to a significant decrease of H. pylori adhesion, but unexpectedly increased IL-8 production. However, PD98059 (a MEK1/2 inhibitor) dramatically down-regulated this cytokine, suggesting MEK/ERK-dependent IL-8 production. Our results suggest that auraptene suppressed H. pylori adhesion and resulting chemokine production by disrupting ERK1/2 activation.

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Citrus Auraptene Reduces Helicobacter pylori Colonization of Glandular Stomach Lesions in Mongolian Gerbils

Cited by 23 publications

References 30 publications

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

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

Characterization of Constituents in the Peel ofCitrus kawachiensis(Kawachibankan)

Suppression of CD74 Expression andHelicobacter pyloriAdhesion by Auraptene Targeting Serum Starvation-Activated ERK1/2 in NCI-N87 Gastric Carcinoma Cells

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