摘要
药物与生物膜的作用对于药物在体内的代谢过程至关重要,因此研究两者的作用对人们认识了解药效及改善其生物性能具有重要意义。由于拉曼光谱是研究分子结构以及分子内、分子间相互作用的重要方法,差示扫描量热技术(DSC)是研究外加物质对生物膜组分相变影响的有力工具。因此,本论文将光谱技术与热力学技术相结合从分子水平上研究了几种人参皂苷分子(Rb1、Re、Rf、Rg1和Rh2)分别与四种生物膜(DPPC、DMPC、DPPG和DPPE)的作用及其对膜结构的影响,主要研究成果如下：
1、利用拉曼光谱研究了五种皂苷分子分别对四种磷脂双层膜的影响。各皂苷分子对不同结构的磷脂双层膜极性头部和疏水性尾部的作用也有差异。在药物浓度逐渐增加的情况下,通过峰值比的变化可以得到皂苷分子对脂双层侧链的作用以及对脂双层膜流动性的影响。
2、利用DSC技术对五种皂苷分子分别与四种生物膜的作用进行了检测。在磷脂双层膜从凝胶态到液晶态发生相转变的过程中,通过各热力学参数如主相变温度(Tm)、半峰宽(△T1／2)及相转变焓值(△H)随药物浓度的变化,诠释了各皂苷分子对脂双层热力学属性的影响。
3、将皂苷分子与磷脂双层膜作用的拉曼光谱与DSC技术结合起来讨论,在此基础上研究不同皂苷分子对同一磷脂膜作用的影响,以及同一皂苷分子对不同磷脂膜作用的差异,这对于我们进一步了解皂苷分子与细胞生物膜的作用机制,具有重要意义。
The interaction between drugs and biomembranes is the first step in the progress of various drugs playing their pharmacodynamics. Thus the research on both interaction is very important and necessary on understanding the efficacy and developing their biological properties. Ginsenosides molecules have become the hotspot topic because of their multi-pharmacutical activities and clinical functions. The study on the influence of ginsenosides on the lipids could provide experimental basises for discussing, realizing and resolving this problem. In this thesis, the differential scanning calorimetry techinique and Raman spectroscopy have been emploied the to study the interaction between five kinds of ginsenoside molecules (Rbl, Re, Rf, Rgl and Rh2) with different category phospholipid liposomes (DPPC, DMPC, DPPG and DPPE). Based on the thermodynamics and from spectroscopy view, the study on the interaction between ginsenoside molecules and biomembranes have been investigated in detailed for the first time on the molecular level. The conclusions are listed as follow:
1. During the study on the interactions between five ginsenosides and DPPC, DMPC lipid bilayers respectively, the drug molecules have effects on the polar head group of phospholipids, however, this kind of interaction hasn't changed the conformation of O-C-C-N+ backbone in the choline group of PC bilayers. The polar head group is still extending parallel to the bilayer surface. Ginsenoside Rbl and Rh2 have significantly increased the fluidity of lipid bilayers. Ginsenoside Re, Rf and Rg1 have no such effects. Moreover, the ginsenosides have showed different degree on perturbating DPPC and DMPC lipisomes. For their different alkyl-chain length, the perturbations of ginsenosides are significantly stronger on DMPC than DPPC.
2. In the study of five ginsenosides' separate affection on the DPPG and DPPE lipid bilayers, Rbl and Rh2 also distinctly decrease their phase-transfer temperature and increased the mobility of acyl chains. Ginsenoside Re, Rf and Rgl have little effects on the fluidity of DPPE and DPPG bilayers. On the difference of molecular structures, the protopanaxadiol ginsenosides have stronger effects on the acyl chains of DPPG and DPPE than the protopanaxtriol ones.
3. From the gel phase to liquid crystalline phase transition, the four kinds of phospholipids have differences on the intermolecular attraction because of their different structure. Therefore, the perturbating degree of ginsenosides is different.
4. As for the same lipid bilayer, there are various affections because of different ginsenoside molecular structures. This is related to the multi-pharmacutical activities of ginsenosides.
引文
[1]Fox C B, Horton R A, Harris J M. Detection of Drug-Membrane Interactions in Individual Phospholipid Vesicles by Confocal Raman Microscopy [J]. Analytical Chemistry 2006,78(14):4918-4924.
[2]Seydel J K, Wiese M. Drug-membrane interactions:analysis, drug distribution, modeling[M]. Wiley 2002,15.Germaney.
[3]陈英杰,窦德强,靳玲.人参的化学成分及药理活性的研究进展与展望[J].沈阳药科大学化学学报,1999,16(2)：151-156.
[4]Qiu Y K, Dou D Q, Cai L, et al. Dammarane-type saponins from Panax quinquefolium and their inhibition activity on human breast cancer MCF-7 cells [J]. Fitoterapia,2009,80(4):219-222.
[5]Rausch W D, Liuz S, Gille G, et al. Neuroprotective effects of ginsenosides [J]. Acta Neurobiologiae Experimentalis,2006,66(4):369-375.
[6]王红艳,徐绥绪,陈英杰,等.人参单体成分药理活性研究的新进展[J].中国药物化学杂志,1992,2(3)：73-78.
[7]Yamaguchi Y, Higashi M, Kobayashi H. Effects of ginsenosides on impaired performance caused by scopolamine in rats [J]. European Journal of Pharmacology, 1996,312(2):149-151.
[8]Yue Patrick Y K, Mak N K, Cheng Y K, et al. Pharmacogenomics and the Yin/Yang actions of ginseng:anti-tumor, angiomodulating and steroid-like activities of ginsenosides [J]. Chin Med,2007,2:6.
[9]Xia C H, Wang G J, Sun R G, et al. Simultaneous determination of ginsenoside Rgl, Re, Rd, Rbl and ophiopogonin D in rat plasma by liquid chromatography/electrospray ionization mass spectrometric method and its application to pharmacokinetic study of 'SHENMAI' injection [J]. Journal of Chromatography B-Analytical Technologies in the biomedical and life sciences,2008,862(1-2):72-78.
[10]Thanh N T, Murthy H N, Yu K W, et al. Effect of oxygen supply on cell growth and saponin production in bioreactor cultures of Panax ginseng [J]. Journal of Plant Plant Physiology,2006,163(12):1337-1341.
[11]Dharmananda S, HerbalG. The nature of ginseng:traditional use, modern research and the question of dosage [J]. Kew,2002,54:34-51.
[12]Fuzzati N. Analysis methods of ginsenosides [J]. Journal of Chromatography B- Analytical Technologies in the Biomedical and Life Sciences,2004,812(1-2):119-133.
[13]Francis G, Kerem Z, Makkar H, et al. The biological action of saponins in animal systems:a review [J]. British Journal of Nutrition,2002,88(6):587-605.
[14]Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds [J]. Journal of Korean Medical Science,2001,16:28-37.
[15]Cheng Y, Shen L H, Zhang J T. Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rbl and its mechanism of action [J]. Acta Pharmacologica Sinica,2005,26(2): 143-149.
[16]Liu Z Q, Luo X Y, Liu G Z, et al. In Vitro Study of the Relationship between the Structure of Ginsenoside and Its Antioxidative or Prooxidative Activity in Free Radical Induced Hemolysis of Human Erythrocytes [J]. Journal of Agricultural and Food Chemistry,2003,51(9):2555-2558.
[17]Ariel O, Levi Y, Hollander N. Signal transduction by CD58:The transmembrane isoform transmits signals outside lipid rafts independently of the GPI-anchored isoform [J]. Cellular Signalling,2009,21(7):1100-1108.
[18]Lingwood D, Kaiser H J, Levental I, et al. Lipid rafts as functional heterogeneity in cell membranes [J]. Biochemical Society Transactions,2009,37:955-960.
[19]Simons K, Ikonen E. Functional rafts in cell membranes [J]. Nature,1997, 387(6633):569-572.
[20]Ikonen E. Roles of lipid rafts in membrane transport [J]. Current Opinion In Cell Biology,2001,13(4):470-477.
[21]Curatolo W. The physical properties of glycolipids [J]. Biochimica et Biophysica Acta-Reviews on Biomembranes 1987,906(2):111-136.
[22]Brown D A, London E. Functions of lipid rafts in biological membranes [J]. Annual Review of Cell and Developmental Biology,1998,14:111-136.
[23]Leekumjorn S, Sum A K. Molecular studies of the gel to liquid-crystalline phase transition for fully hydrated DPPC and DPPE bilayers [J]. Biochimica et Biophysica acta-Biomembranes,2007,768(2):354-365.
[24]Singer S J, Nicolson G L. The fluid mosaic model of the structure of cell membranes [Z].1972:173.
[25]隋森芳.膜分子生物学[M].高等教育出版社,2003：5.
[26]Gabius H J, Gabius S. Glycosciences:status and perspectives [M]. Chapman & Hall. London,1997.
[27]Bondar O P, Rowe E S. Differential scanning calorimetric study of the effect of vitamin D-3 on the thermotropic phase behavior of lipids model systems [J]. Biochimica et biophysica acta-Biomembranes,1995,1240(2):125-132.
[28]Lucio M, Nunes C, Gaspar D, et al. Effect of anti-inflammatory drugs in phosphatidylcholine membranes:A fluorescence and calorimetric study [J]. Chemical Physics Letters,2009,471(4-6):300-309.
[29]Chian-Chen C Y. Magnolol encapsulated by different acyl chain length of liposomes on inhibiting proliferation of smooth muscle cells [J]. Journal of the Taiwan Institute of Chemical Engineers,2009,40(4):380-386.
[30]Jain M K, In R C. Membrane fluidity in biology [M]. Academic Press, America, 1983,1:1-37.
[31]Seydel U, Labischinski H, Kastowsky M, et al. Phase behavior,supramolecular-conformation of lipopolysaccharide [J]. Immunobiology,1993, 187(3-5):191-211.
[32]Seydel U, Wiese A, Schromm A B, et al. A biophysical view on the function and activity of endotoxins [J]. Endotoxin in Health and Disease,1999:195-220.
[33]Blume A. Thermochim. Acta,1991,193:299-347.
[34]Israelachvili J N. Intermolecular and Surface Forces [M]. Academic Press,1991.
[35]Epand R F, Ramamoorthy A, Epand R M. Membrane lipid composition and the interaction of pardaxin:The role of cholesterol [J]. Protein and Peptide Letters,2006, 13(1):1-5.
[36]Silvius J R, Del G D, Lafleur M. Cholesterol at different bilayer concentrations can promote or antagonize lateralsegregation of phospholipids of differing acyl chain length [J]. Biochemistry,1996,35(48):15198-15208.
[37]Wonerow P, Obergfell A, Wilde J I, et al. Differential role of glycolipid-enriched membrane domains in glycoprotein VI-and integrin-mediated phospholipase C gamma 2 regulation in platelets [J]. Biochemical Journal,2002,364(3):755-765.
[38]Yamamura S, Handa K, Hakomori S. A close association of GM3 with c-Src and Rho in GM3-enriched microdomains at the B16 melanoma cell surface membrane:a preliminary note [J]. Biochem. Biophys. Res. commun,1997,236:218-222.
[39]Iwabuchi K, Handa K, Hakomori S. Separation of " glycosphingolipid signaling oomain" from caveolin-containing membrane fraction in mouse melanoma B16 Cells and Its Role in Cell adhesion coupled with signaling [J]. J. Biol. Chem.,1998,273: 33766-33773.
[40]Tsunoda T, Imura T, Kadota M, et al. Effects of lysozyme and bovine serum albumin on membrane characteristics of dipalmitoylphosphatidylglycerol liposomes [J]. Colloids and Surfaces B-Biointerfaces,2001,20(2):155-163.
[41]Lohner K. Development of novel antimicrobial agents:emerging strategies [M]. Horizon Scientific Press,2001.
[42]Conrad R S, Howard M J, Garrison R C, et al. The effects of daptomycin on chemical composition and morphology of staphylococcus aureus [J]. Proc. Okla. Acad. Sci.,1998,78:15-22
[43]Yeagle P L. The membranes of cells [M]. Academic Press Inc.,1993.
[44]Bulkin B J. Raman spectroscopic study of human erythrocythrocyte-membranes [J]. Biochimica et Biophysica acta,1972,274(2):649.
[45]Spiro T G, Gaber B P. Laser raman-scattering as a probe of protein-structure [J]. Annual revies of Biochemistry,1977,46:553-572.
[46]Snyder R G, Scherer J R, Gaber B P. Effects of chain packing and chain mobility on the raman-spectra of biomembranes [J]. Biochimica et Biophysic Acta,1980,601(1): 47-53.
[47]Yager P, Peticolas W L. Statistical mechanical analysis of raman spectroscopic order parameter changes in pressure-induced lipid bilayer phase-transitions [J]. Biophysical Journal,1980,31(3):359-370.
[48]Lis L J, Kauffman J W, Shriver D F. Effedt of ions on phospholipid layer structure as indicated by raman-spectroscopy [J]. Biochimica et biophysica acta,1975,406(4): 453-464.
[49]Zhao B, Li X M, Zhao D Q, et al. Interaction of scopolamine and cholesterol with sphingomyelin bilayers by FT-Raman spectroscopy [J]. Spectroscopy Letters,1998, 31(8):1825-1837.
[50]赵雨,赵大庆,席时权,等.鞘磷脂与胆固醇相互作用的拉曼光谱研究[J].光散射学报,1999,11(2)：165-169.
[51]Li X M, Zhao B, Zhao D Q, et al Interaction of La3+ and cholesterol with dipalmitoylphosphatidylglycerol bilayers by FT-Raman spectroscopy [J]. Thin Solid Films,1996,284-285:762-764.
[52]Kyrikou I, Hadjikakou S K, Kovala-Demertzi D, et al. Effects of non-steroid anti-inflammatory drugs in membrane bilayers [J]. Chemistry and Physics of Lipids, 2004,132(2):157-169.
[53]Gardikis K, Hatziantoniou S, Viras K, et al. Effect of a bioactive curcumin derivative on DPPC membrane:A DSC and Raman spectroscopy study [J]. Thermochimica acta,2006,447(1):1-4.
[54]Csiszar A, Koglin E, Meier R J, et al. The phase transition behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) model membrane influenced by 2,4-dichlorophenol-an FT-Raman Spectroscopy Study [J]. Chemistry and Physics of Lipids,2006,139(2):115-124.
[55]Ianoul A, Westwick H, Nowacka L, et al. Interactions of lactoferricin B derivatives with model cell membrane studied by Raman spectroscopy [J]. Journal of Raman Spectroscopy,2007,38(2):200-204.
[56]Yuan C B, Zhao D Q, Ni J Z. A Raman study of the effect of trivalent lanthanide lions on the conformational disorder in acyl chains of phospholipid bilayers [J]. Chemieal Research in Chinese Universities,1994,10(4):377.
[57]Akutsu H. Direct determination by Raman-scattering of the conformation of the choline group in phospholipid-bilayers [J]. Biochemistry,1981,20(26):7359-7366.
[58]Lamba O P, Borchman D, Sinha S K, et al. Structure and molecular conformation of anhydrous and of aqueous sphingomyelin bilayers determined by infrared and Raman spectroscopy [J]. Journal of molecular structure,1991,248(1):1-24.
[59]Inoue T, Yanagihara S, Misono Y, et al. Effect of fatty acids on phase behavior of hydrated dipalmitoylphosphatidylcholine bilayer:saturated versus unsaturated fatty acids [J]. Chemistry and Physics of Lipids,2001,109(2):117-133.
[60]Mimeault M, Bonenfant D. FT-IR spectroscopic analyses of the temperature and pH influences on stratum corneum lipid phase behaviors and interactions [J]. Talanta,2002, 56(3):395-405.
[61]Cieslik-Boczula K, Czarnik-Matusewicz B, Perevozkina M, et al. ATR-IR spectroscopic study of the structural changes in the hydrophobic region of ICPAN/DPPC bilayers [J]. Journal of Molecular Structure,2008,878(1-3):162-168.
[62]Tanphalchttr N, Namking M, Tupper S, et al. Gossypol effects on the structure and dynamics of phospholipid bilayers:A FT-IR study [J]. Chemistry and Physics of Lipids, 1995,75:119-125.
[63]Blume A, Hubner W, Messner G. Fourier-transform infrared-spectroscopy of C-13=O-labeled phospholipids hydrogen-bonding to carbonyl groups [J]. Biochemistry, 1988,27(21):8239-8249.
[64]Janiak M J, Small D M, Shipley G G. Temperature and compositional dependence of the structure of hydrated dimyristoyl lecithin [J]. Jounal of Biological Chemistry, 1979,254(13):6068-6078.
[65]Lefe Vre T, Subirade M. Interaction of b-lactoglobulin with phospholipid bilayers:a molecular level elucidation as revealed by infrared spectroscopy [J]. International Journal of Biological Macromolecules,2000,28:59-67.
[66]Katarzyna C B, Aleksander K. The effect of 3-pentadecylphenol on DPPC bilayers ATR-IR and P-31 NMR studies [J]. Biophysical Chemistry,2009,140(1-3):51-56.
[67]Bensikaddour H, Snoussi K, Lins L, et al. Interactions of ciprofloxacin with DPPC and DPPG:Fluorescence anisotropy, ATR-FTIR and P-31 NMR spectroscopies and conformational analysis [J]. Biochimica et Biophysica Acta-Biomembranes,2008, 1778(11):2535-2543.
[68]Binning G, Quate C F. Atomic force microscope [J]. Physical Review Letters,1986, 56:930-933.
[69]Engel A. Microscopic assessment of membrane protein structure and function [J]. Histochemistry and Cell Biology,2003,120(2):93-102.
[70]Ikai A. Biological applications of atomic force microscopy [J]. Tanpakushitsu Kakusan Koso,1994,39(7):1298-1304.
[71]Dufrene Y F, Boland T, Schneider J W, et al. Characterization of the physical properties of model biomembranes at the nanometer scale with the atomic force microscope [J]. Faraday Discussions,1998:79-94.
[72]Nielsen L K, Bjornholm T, Mouritsen O G. Critical phenomena-Fluctuations caught in the act [J]. Nature,2000,404(6776):352.
[73]Takeyasu K, Omote H, Nettikadan S, et al. Molecular imaging of Escherichia coli FOF1-ATPase in reconstituted membranes using atomic force microscopy [J]. Febs Letters,1996,392(2):110-113.
[74]Nagao E, Kaneko O, Dvorak J A. Plasmodium falciparum-infected erythrocytes: Qualitative and quantitative analyses of parasite-induced knobs by atomic force microscopy [J]. Journal of Structural Biology,2000,130(1):34-44.
[75]Yang J, Tamm L K, Tillack T W, et al. New approach for atomic force microscopy of membrane-proteins-the imaging of cholera-toxin [J]. Journal of Molecular Biology, 1993,229(2):286-290.
[76]Tokumasu F, Jin A J, Dvorak J A. Lipid membrane phase behaviour elucidated in real time by controlled environment atomic force microscopy [J]. Journal of Electron Microscopy,2002,51(1):1-9.
[77]Parimi S, Barnes T J, Prestidge C A. PAMAM Dendrimer Interactions with Supported Lipid Bilayers:A Kinetic and Mechanistic Investigation [J]. Langmuir,2008, 24(23):13532-13539.
[78]Epand R F, Savage P B, Epand R M. Bacterial lipid composition and the antimicrobial efficacy of cationic steroid compounds (Ceragenins) [J]. Biochimica et Biophysica Acta-Biomembranes,2007,1768(10):2500-2509.
[79]Maswadeh H, Demetzos C, Dimas K, et al. In-vitro cytotoxic/cytostatic activity of anionic liposomes containing vinblastine against leukaemic human cell lines [J]. Journal of Pharmacy and Pharmacology,2002,54(2):189-196.
[80]Bonora S, Di Foggia M, Iafisco M. DSC and Raman study on the interaction of DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane] with liposomal phospholipids [J]. Pesticide Biochemistry and Physiology,2008,92(3):144-149.
[81]Panicker L. Influence of the leprosy drug, dapsone on the model membrane dipalmitoyl phosphatidylethanolamine [J]. Thermochimica Acta 2006,447(2):123-130.
[82]Klajnert B, Janiszewska J, Urbanczyk-I ipkowska Z, et al. DSC studies on interactions between low molecular mass peptide dendrimers and model lipid membranes [J]. International Journal of Pharmaceutics,2006,327(1-2):145-152.
[83]Lepore L S, Ellena J F, Cafiso D S. Comparison of the lipid acyl chain dynamics between small and large unilamellar vesicles [J]. Biophysical Journal,1992,61: 767-775.
[84]Mellier A. Infrared study of phospholipid hydration-new thermodynamic data about the main phase-transition of saturated phosphatidylcholine water multidispersions [J]. Chemistry and Physics of Lipids,1989,51(1):23-29.
[85]Garidel P, Richter W, Rapp G, et al. Structural and morphological investigations of the formation of quasi-crystalline phases of 1, 2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) [J]. Physical Chemistry Chemical Physics,2001,3(8):1504-1513.
[86]张志鸿等.膜生物物理[M].高等教育出版社,1987,49.
[87]Prochazka M, Stepanek J, Turpin P Y. Interaction of phospholipid dispersions with water-soluble porphyrins as monitored by their Raman temperature profiles [J]. Chemistry and Physics of Lipids,2004,132(2):145-156.
[88]Roche Y, Peretti P, Bernard S. DSC and Raman studies of the side chain length effect of ubiquinones on the thermotropic phase behavior of liposomes [J]. Thermochimica Acta,2006,447(1):81-88.
[89]Kyrikou I, Benetis N P, Chatzigeorgiou P, et al. Interactions of the dipeptide paralysin β-Ala-Tyr and the aminoacid Glu with phospholipid bilayers [J].Biochimica et Biophysica Acta-Biomembranes,2008,1778(1):113-124.
[90]Gardikis K, Hatziantoniou S, Viras K, et al. A DSC and Raman spectroscopy study on the effect of PAMAM dendrimer on DPPC model lipid membranes [J]. International Journal of Pharmaceutics,2006,318(1-2):118-123.
[91]Stott B M, Vu M P, McLemore C O, et al. Use of fluorescence to determine the effects of cholesterol on lipid behavior in sphingomyelin liposomes and erythrocyte membranes [J]. Journal of Lipid Research,2008,49(6):1202-1215.
[92]Wang S X, Cai G P, Sui S. F. Intrinsic fluorescence study of the interaction of human apolipoprotein H with phospholipid vesicles [J]. Biochemistry,1999,38(29): 9477-9484.
[93]王苏民,黄芬.31P-核磁共振波谱研究山莨菪碱对磷脂酰乙醇胺脂质体多形性的影响[J].科学通报,1985：1107-1109.
[94]何琦,黄芬.山蓑若碱与神经鞘磷脂脂质体的相互作用[J].生物物理学报,1986,2(1)：14-19.
[95]Kyrikou I, Georgopoulos A, Hatziantoniou S, et al. A comparative study of the effects of cholesterol and sclareol, a bioactive labdane type diterpene, on phospholipid bilayers [J]. Chemistry and Physics of Lipids,2005,133(2):125-134.
[96]Qu X B, Zhao Y, Song Y, et al. Raman spectroscopy study on the structure of ginsenoside Rg3 [J]. Spectroscopy and spectral analysis,2008,28(3):569-571.
[97]Jiang Q S, Huang X N, Dai Z K, et al. Inhibitory effect of ginsenoside Rb-1 on cardiac hypertrophy induced by monocrotaline in rat [J]. Journal of Ethnopharmacology, 2007,111(3):567-572.
[98]Shen L H, Zhang J T. Ginsenoside Rgl increases ischemia-induced cell proliferation and survival in the dentate gyrus of adult gerbils [J]. Neuroscience Letters, 2003,344(1):1-4.
[99]Nakata H, Kikuchi Y, Tode T, et al. Inhibitory effects of ginsenoside Rh-2 on tumor growth in nude mice bearing human ovarian cancer cells [J]. Japanese Journal of Cancer Research,1998,89(7):733-740.
[100]Radad K, Gille G, Moldzio R, et al. Ginsenosides Rbl and Rgl effects on survival and neurite growth of MPP+-affected mesencephalic dopaminergic cells [J]. Journal of Neural Transmission,2004,111(1):37-45.
[101]Shinkai K, Akedo H, Mukai M, et al. Inhibition of in vitro tumor cell invasion by ginsenoside Rg(3) [J]. Japanese Journal of Cancer Research,1996,87(4):357-362.
[102]Brandenburg K, Garidel P, Howe J, et al. What can calorimetry tell us about changes of three-dimensional aggregate structures of phospholipids and glycolipids? [J]. Thermochimica Acta,2006,445(2):133-143.
[103]Goniotaki M, Hatziantoniou S, Dimas K, et al. Encapsulation of naturally occurring flavonoids into liposomes:physicochemical properties and biological activity against human cancer cell lines [J]. Journal of Pharmacy and Pharmacology,2004,56(10): 1217-1224.
[104]Matsingou C, Hatziantoniou S, Georgopoulos A, et al. Labdane-type diterpenes: thermal effects on phospholipid bilayers, incorporation into liposomes and biological activity [J]. Chemistry and Physics of Lipids,2005,138(1-2):1-11.
[105]Bonora S, Torreggiani A, Fini G. DSC and Raman study on the interaction between polychlorinated biphenyls (PCB) and phospholipid liposomes [J]. Thermochimica Acta, 2003,408(1-2):55-65.
[106]Nakata H, Kikuchi Y, Tode T, et al. Inhibitory effects of ginsenoside Rh-2 on tumor growth in nude mice bearing human ovarian cancer cells [J]. Japanese Journal of Cancer Research,1998,89(7):733-740.
[107]Odashima S, Nakayabu Y, Honjo N. Induction of phenotypic reverse transformation by ginsenosides in cultured Morris hepatoma cells [J]. Eur J Cancer,1979,15:885-892.
[108]Max J J, Chapados C. Glucose and fructose hydrates in aqueous solution by IR spectroscopy [J]. Journal of Physical Chemistry A,2007,111(14):2679-2689.
[109]Shang X H, Hui G, Zhao Y, et al. Structure and Vibrational Spectroscopy of Ginsenoside Re:Density Functional Theory Study [J]. Spectroscopy and Spectral Analysis,2009,29(10):2765-2768.
[110]Holopainen J M, Lemmich J, Richter F, et al. Dimyristoylphosphatidylcholine/C16: 0-ceramide binary liposomes studied by differential scanning calorimetry and wide-and small-angle X-ray scattering [J]. Biophysical Journal,2000,78(5):2459-2469.
[111]Shin H R, Kim J Y, Yun T K, et al. The cancer-preventive potential of Panax
ginseng:a review of human and experimental evidence [J]. Cancer Causes & Control, 2000,11(6):565-576.
[112]Wang X M, Sakuma T, Asafu-Adjaye E, et al. Determination of ginsenosides in plant extracts from Panax ginseng and Panax quinquefolius L. by LC/MS/MS [J]. Analytical Chemistry,1999,71(8):1579-1584.
[113]Lucio M, Nunes C, Gaspar D, et al. Effect of anti-inflammatory drugs in phosphatidylcholine membranes:A fluorescence and calorimetric study [J]. Chemical Physics Letters,2009,471(4-6):300-309.
[114]Hosokawa T, Sami M, Kato Y, et al. Alteration in the temperature-dependent content release property of thermosensitive liposomes in plasma [J]. Chemical & Pharmaceutical Bulletin,2003,51(11):1227-1232.
[115]Garidel P, Blume A. Miscibility of phosphatidylethanolamine-phosphatidylglycerol mixtures as a function of pH and acyl chain length [J]. European Biophysics Journal with Biophysics Letters,2000,28(8):629-638.
[116]Ortiz A, Teruel J A, Espuny M J, et al. Interacionsof a Rhodococcus sp. biosurfactant trehalose lipid with phosphatidylethanolamine membranes [J]. Biochimica et Biophysica Acta-Biomembranes,2008,1778:2806-2813.
[117]Rogers H J., Perkins H. R., Ward J B. Microbial cell walls and membranes [J]. Biosynthesis of Peptidoglycan,1980,University Press, Cambridge.
[118]Leekumjorn S, Sum A K. Molecular studies of the gel to liquid-crystalline phase transition for fully hydrated DPPC and DPPE bilayers [J]. Biochimica et biophysica acta-Biomembranes,2007,1768(2):354-365.