title: Effect of glycyrrhetinic acid on lipid raft model at the air/water interface.
abstract: To investigate an interfacial behavior of the aglycon of glycyrrhizin (GC), glycyrrhetinic acid (GA), with a lipid raft model consisting of equimolar ternary mixtures of N-palmitoyl sphingomyelin (PSM), dioleoylphosphatidylcholine (DOPC), and cholesterol (CHOL), Langmuir monolayer techniques were systematically conducted. Surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms showed that the adsorbed GA at the air/water interface was desorbed into the bulk upon compression of the lipid monolayer. In situ morphological analysis by Brewster angle microscopy and fluorescence microscopy revealed that the raft domains became smaller as the concentrations of GA in the subphase (CGA) increased, suggesting that GA promotes the formation of fluid networks related to various cellular processes via lipid rafts. In addition, ex situ morphological analysis by atomic force microscopy revealed that GA interacts with lipid raft by lying down at the surface. Interestingly, the distinctive striped regions were formed at CGA=5.0 μM. This phenomenon was observed to be induced by the interaction of CHOL with adsorbed GA and is involved in the membrane-disrupting activity of saponin and its aglycon. A quantitative comparison of GA with GC (Sakamoto et al., 2013) revealed that GA interacts more strongly with the raft model than GC in the monolayer state. Various biological activities of GA are known to be stronger than those of GC. This fact allows us to hypothesize that differences in the interactions of GA/GC with the model monolayer correlate to their degree of exertion for numerous activities.
authors.affiliation: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: s.sakamoto@phar.kyushu-u.ac.jp.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Uto
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shoyama
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000388:Air; D002784:Cholesterol / Q000737:chemistry*; D006034:Glycyrrhetinic Acid / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry; D013109:Sphingomyelins / Q000737:chemistry; D013499:Surface Properties; D014867:Water
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D012503:Saponins; D013109:Sphingomyelins; C033171:palmitoylsphingomyelin; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D019695:Glycyrrhizic Acid; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine; D006034:Glycyrrhetinic Acid
keywords: Glycyrrhetinic acid (GA); Glycyrrhizin (GC); Langmuir monolayer; Lipid raft; Membrane-disrupting activity