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Garlic allyl derivatives interact with membrane lipids to modify the membrane fluidity

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Journal of Biomedical Science

Abstract

As a novel approach to the mode of medicinal action of garlic, its constituents were comparatively studied with respect to their interactions with membrane lipids to modify the membrane fluidity. Allyl derivatives rigidified tumor cell and platelet model membranes consisting of unsaturated phospholipids and cholesterol at 20–500 μM with the potency being diallyl trisulfide (DATS) > diallyl disulfide (DADS) by preferentially acting on the hydrocarbon cores of lipid bilayers. They were also effective in rigidifying candida cell model membranes prepared with ergosterol and phospholipids at 100–500 μM with the potency being DADS > DATS > diallyl sulfide (DAS), but not bacteria cell model membranes without ergosterol. Alliin, a precursor of these DASs, was not active on any membranes at 500 μM. Both relative intensity and selectivity in membrane effects correlated with those in antiproliferative, antiplatelet and antimicrobial effects. In cell culture experiments, membrane-active DASs inhibited the growth of tumor cells cultured for 24 and 48 h at 20–500 μM to show the potency being DATS > DADS, together with rigidifying cell membranes by acting on their deeper regions more intensively. However, membrane-inactive allyl derivatives were not growth-inhibitory on tumor cells. The membrane lipid interactions of DASs appear to be one of possible mechanisms underlying different effects of garlic.

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Abbreviations

DAS:

Diallyl sulfide

DADS:

Diallyl disulfide

DATS:

Diallyl trisulfide

DPPC:

1,2-Dipalmitoylphosphatidylcholine

POPC:

1-Palmitoyl-2-oleoylphosphatidylcholine

POPE:

1-Palmitoyl-2-oleoylphosphatidylethanolamine

SOPS:

1-Stearoyl-2-oleoylphosphatidylserine

POPG:

1-Palmitoyl-2-oleoylphosphatidylglycerol

SM:

Sphingomyelin

DPH:

1,6-Diphenyl-1,3,5-hexatriene

TMA-DPH:

1-(4-Trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene

2-AS:

2-(9-Anthroyloxy)stearic acid

6-AS:

6-(9-Anthroyloxy)stearic acid

9-AS:

9-(9-Anthroyloxy)stearic acid

12-AS:

12-(9-Anthroyloxy)stearic acid

16-AP:

16-(9-Anthroyloxy)palmitic acid

PBS:

Phosphate-buffered saline of pH 7.4

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Acknowledgement

This study was partly supported by a grant from the San-Ei Gen Foundation for Food Chemical Research.

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Authors and Affiliations

  1. Department of Dental Basic Education, Asahi University School of Dentistry, Building 3, 1851 Hozumi, Mizuho, Gifu, 501-0296, Japan

    Hironori Tsuchiya

  2. Department of Oral Pathology, Asahi University School of Dentistry, Mizuho, Gifu, Japan

    Motohiko Nagayama

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  1. Hironori Tsuchiya
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  2. Motohiko Nagayama
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Correspondence to Hironori Tsuchiya.

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Tsuchiya, H., Nagayama, M. Garlic allyl derivatives interact with membrane lipids to modify the membrane fluidity. J Biomed Sci 15, 653–660 (2008). https://doi.org/10.1007/s11373-008-9257-8

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