β-环糊精及衍生物作为生物活性分子研究进展
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摘要
β-环糊精为环状低聚糖,具有疏水内腔与亲水外层,其疏水内腔可与胞内胆固醇等脂质形成包合物,促进胞内蓄积脂质外排,调控胞内脂质稳态。近年来以β-环糊精及其衍生物为生物活性分子用于治疗尼曼-皮克C型疾病、阿尔兹海默病、缺血缺氧性脑病、动脉粥样硬化、癌症等疾病受到广泛关注。本文综述了β-环糊精及其衍生物作为生物活性分子在脂质失衡相关疾病治疗中的研究进展,为开发调控胞内脂质稳态类生物活性分子提供参考。
β-Cyclodextrins are cyclic oligosaccharides that have a lipophilic cavity and a hydrophilic external surface.β-Cyclodextrins have the ability to encapulate hydrophobic molecule such as cholesterol,sphingolipids intracellularly,and promote the efflux of cholesterol and other lipids from the cell,finally regulate the homeostasis of cholesterol and other lipids.In recent years,researches on pharmacodynamics of β-cyclodextrins as well as their derivatives that have been used as active pharmaceutical ingredient for Niemann-Pick Type C disease,Alzheimer's disease,hypoxic-ischemic encephalopathy,atherosclerosis,cancer and other diseases have made some progress.This article summarized the research progress of β-cyclodextrins as well as their derivatives used as active pharmaceutical ingredient in various diseases,and aimed to provide reference for the advancement of β-cyclodextrin as well as their derivatives in the clinical research of various diseases through regulating lipid homeostasis.
β-Cyclodextrins are cyclic oligosaccharides that have a lipophilic cavity and a hydrophilic external surface.β-Cyclodextrins have the ability to encapulate hydrophobic molecule such as cholesterol,sphingolipids intracellularly,and promote the efflux of cholesterol and other lipids from the cell,finally regulate the homeostasis of cholesterol and other lipids.In recent years,researches on pharmacodynamics of β-cyclodextrins as well as their derivatives that have been used as active pharmaceutical ingredient for Niemann-Pick Type C disease,Alzheimer's disease,hypoxic-ischemic encephalopathy,atherosclerosis,cancer and other diseases have made some progress.This article summarized the research progress of β-cyclodextrins as well as their derivatives used as active pharmaceutical ingredient in various diseases,and aimed to provide reference for the advancement of β-cyclodextrin as well as their derivatives in the clinical research of various diseases through regulating lipid homeostasis.
引文
[1] CRINI G. Review:a history of cyclodextrins[J]. Chem Rev,2014,114(21):10940-10975.
[2] OLIVERI V,BELLIA F,PIETROPAOLO A,et al.Unusual Cyclodextrin Derivatives as a New Avenue to Modulate Self-and Metal-Induced Abeta Aggregation[J]. Chemistry(Easton),2015,21(40):14047-14059.
[3] LECLERCQ L.Interactions between cyclodextrins and cellular components:Towards greener medical applications?[J].Beilstein J Org Chem,2016,12(1):2644-2662.
[4] ABI-MOSLEH L,INFANTE R E,RADHAKRISHNAN A,et al. Cyclodextrin overcomes deficient lysosome-toendoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells[J].Proc Natl Acad Sci U S A,2009,106(46):19316-19321.
[5] KWON H J,ABI-MOSLEH L,WANG M L,et al.Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol[J].Cell,2009,137(7):1213-1224.
[6] PEAKE K B,VANCE J E.Defective cholesterol trafficking in Niemann-Pick C-deficient cells[J].FEBS Lett,2010,584(13):2731-2739.
[7] VITE C H,BAGEL J H,SWAIN G P,et al.Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease[J].Sci Transl Med,2015,7(276):276ra26.
[8] VANIER M T. Niemann-Pick disease type C[J].Orphanet J Rare Dis,2010(5):16.
[9] ROSZELL B R,TAO J Q,YU K J,et al.Pulmonary abnormalities in animal models due to Niemann-Pick type C1(NPC1)or C2(NPC2)disease[J].PLoS One,2013,8(7):e67084.
[10] MURALIDHAR A,BORBON I A,ESHARIF D M,et al.Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1(-)/(-)mice[J].Mol Genet Metab,2011,103(2):142-147.
[11] LIU B,RAMIREZ C M,MILLER A M,et al.Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid[J].J Lipid Res,2010,51(5):933-944.
[12] CAMARGO F,ERICKSON R P,GARVER W S,et al.Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease[J].Life Sci,2001,70(2):131-142.
[13] LIU S M,COGNY A,KOCKX M,et al.Cyclodextrins differentially mobilize free and esterified cholesterol from primary human foam cell macrophages[J]. J Lipid Res,2003,44(6):1156-1166.
[14] LIU B,TURLEY S D,BURNS D K,et al.Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/-mouse[J]. Proc Natl Acad Sci U S A,2009,106(7):2377-2382.
[15] MCGEER P L,MCGEER E G. NSAIDs and Alzheimer disease:epidemiological,animal model and clinical studies[J].Neurobiol Aging,2007,28(5):639-647.
[16] MALNAR M,HECIMOVIC S,MATTSSON N,et al.Bidirectional links between Alzheimer's disease and Niemann-Pick type C disease[J].Neurobiol Dis,2014(72 Pt A):37-47.
[17] OHM T G,TREIBER-HELD S,DISTL R,et al.Cholesterol and tau protein--findings in Alzheimer's and Niemann Pick C's disease[J]. Pharmacopsychiatry,2003,36(Suppl2):S120-S126.
[18] YAMAZAKI T,CHANG T Y,HAASS C,et al.Accumulation and aggregation of amyloid beta-protein in late endosomes of Niemann-pick type C cells[J].J Biol Chem,2001,276(6):4454-4460.
[19] YANG D S,STAVRIDES P,SAITO M,et al. Defective macroautophagic turnover of brain lipids in the Tg CRND8Alzheimer mouse model:prevention by correcting lysosomal proteolytic deficits[J]. Brain,2014,137(Pt 12):3300-3318.
[20] VAN ECHTEN-DECKERT G,WALTER J.Sphingolipids:critical players in Alzheimer's disease[J].Prog Lipid Res,2012,51(4):378-393.
[21] YAO J,HO D,CALINGASAN N Y,et al.Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease[J].J Exp Med,2012,209(13):2501-2513.
[22] YANG D S,STAVRIDES P,KUMAR A,et al.Cyclodextrin has conflicting actions on autophagy flux in vivo in brains of normal and Alzheimer model mice[J].Hum Mol Genet,2017,26(5):843-859.
[23] KNIGHT E M,WILLIAMS H N,STEVENS A C,et al.Evidence that small molecule enhancement of beta-hexosaminidase activity corrects the behavioral phenotype in Dutch APP(E693Q)mice through reduction of ganglioside-bound Abeta[J]. Mol Psychiatry,2015,20(1):109-117.
[24] RIVERS J R,MAGGO S D,ASHTON J C.Neuroprotective effect of hydroxypropyl-beta-cyclodextrin in hypoxia-ischemia[J].Neuroreport,2012,23(3):134-138.
[25] FRANK C,RUFINI S,TANCREDI V,et al. Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus[J].Exp Neurol,2008,212(2):407-414.
[26] SARI P,KERR D S. Domoic acid-induced hippocampal CA1 hyperexcitability independent of region CA3 activity[J].Epilepsy Res,2001,47(1-2):65-76.
[27] YURDAGUL A J R,FINNEY A C,WOOLARD M D,et al. The arterial microenvironment:the where and why of atherosclerosis[J]. Biochem J,2016,473(10):1281-1295.
[28] BACK M,HANSSON G K. Anti-inflammatory therapies for atherosclerosis[J].Nat Rev Cardiol,2015,12(4):199-211.
[29] LI H,EL-DAKDOUKI M H,ZHU D C,et al.Synthesis of beta-cyclodextrin conjugated superparamagnetic iron oxide nanoparticles for selective binding and detection of cholesterol crystals[J].Chem Commun(Camb),2012,48(28):3385-3387.
[30] ZIMMER S,GREBE A,BAKKE S S,et al. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming[J].Sci Transl Med,2016,8(333):333ra50.
[31] JEURISSEN M L J,WALENBERGH S M A,HOUBEN T,et al.Prevention of ox LDL uptake leads to decreased atherosclerosis in hematopoietic NPC1-deficient Ldlr(-/-)mice[J].Atherosclerosis,2016(255):59-65.
[32] DI MINNO G,SPADARELLA G,CAFARO G,et al.Systematic reviews and meta-analyses for more profitable strategies in peripheral artery disease[J]. Ann Med,2014,46(7):475-489.
[33] NORGREN L,HIATT W R,DORMANDY J A,et al.Inter-Society Consensus for the Management of Peripheral Arterial Disease(TASC II)[J]. J Vasc Surg,2007,45(Suppl S):S5-67.
[34] ZHAO Y,VANHOUTTE P M,LEUNG S W. Vascular nitric oxide:Beyond e NOS[J].J Pharmacol Sci,2015,129(2):83-94.
[35] QI X,YUAN Y,XU K,et al.(2-Hydroxypropyl)-betaCyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis[J]. PLoS One,2015,10(5):e0125323.
[36] MULAS M F,ABETE C,PULISCI D,et al.Cholesterol esters as growth regulators of lymphocytic leukaemia cells[J].Cell Prolif,2011,44(4):360-371.
[37] GEORGE K S,WU S.Lipid raft:A floating island of death or survival[J]. Toxicol Appl Pharmacol,2012,259(3):311-319.
[38] YAN J,LI Q F,WANG L S,et al. Methyl-betacyclodextrin induces programmed cell death in chronic myeloid leukemia cells and,combined with imatinib,produces a synergistic downregulation of ERK/SPK1signaling[J].Anticancer Drugs,2012,23(1):22-31.
[39] LOFTSSON T,BREWSTER M E.Pharmaceutical applications of cyclodextrins:basic science and product development[J].J Pharm Pharmacol,2010,62(11):1607-1621.
[40]YOKOO M,KUBOTA Y,MOTOYAMA K,et al. 2-Hydroxypropyl-beta-Cyclodextrin Acts as a Novel Anticancer Agent[J].PLoS One,2015,10(11):e0141946.
[2] OLIVERI V,BELLIA F,PIETROPAOLO A,et al.Unusual Cyclodextrin Derivatives as a New Avenue to Modulate Self-and Metal-Induced Abeta Aggregation[J]. Chemistry(Easton),2015,21(40):14047-14059.
[3] LECLERCQ L.Interactions between cyclodextrins and cellular components:Towards greener medical applications?[J].Beilstein J Org Chem,2016,12(1):2644-2662.
[4] ABI-MOSLEH L,INFANTE R E,RADHAKRISHNAN A,et al. Cyclodextrin overcomes deficient lysosome-toendoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells[J].Proc Natl Acad Sci U S A,2009,106(46):19316-19321.
[5] KWON H J,ABI-MOSLEH L,WANG M L,et al.Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol[J].Cell,2009,137(7):1213-1224.
[6] PEAKE K B,VANCE J E.Defective cholesterol trafficking in Niemann-Pick C-deficient cells[J].FEBS Lett,2010,584(13):2731-2739.
[7] VITE C H,BAGEL J H,SWAIN G P,et al.Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease[J].Sci Transl Med,2015,7(276):276ra26.
[8] VANIER M T. Niemann-Pick disease type C[J].Orphanet J Rare Dis,2010(5):16.
[9] ROSZELL B R,TAO J Q,YU K J,et al.Pulmonary abnormalities in animal models due to Niemann-Pick type C1(NPC1)or C2(NPC2)disease[J].PLoS One,2013,8(7):e67084.
[10] MURALIDHAR A,BORBON I A,ESHARIF D M,et al.Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1(-)/(-)mice[J].Mol Genet Metab,2011,103(2):142-147.
[11] LIU B,RAMIREZ C M,MILLER A M,et al.Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid[J].J Lipid Res,2010,51(5):933-944.
[12] CAMARGO F,ERICKSON R P,GARVER W S,et al.Cyclodextrins in the treatment of a mouse model of Niemann-Pick C disease[J].Life Sci,2001,70(2):131-142.
[13] LIU S M,COGNY A,KOCKX M,et al.Cyclodextrins differentially mobilize free and esterified cholesterol from primary human foam cell macrophages[J]. J Lipid Res,2003,44(6):1156-1166.
[14] LIU B,TURLEY S D,BURNS D K,et al.Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/-mouse[J]. Proc Natl Acad Sci U S A,2009,106(7):2377-2382.
[15] MCGEER P L,MCGEER E G. NSAIDs and Alzheimer disease:epidemiological,animal model and clinical studies[J].Neurobiol Aging,2007,28(5):639-647.
[16] MALNAR M,HECIMOVIC S,MATTSSON N,et al.Bidirectional links between Alzheimer's disease and Niemann-Pick type C disease[J].Neurobiol Dis,2014(72 Pt A):37-47.
[17] OHM T G,TREIBER-HELD S,DISTL R,et al.Cholesterol and tau protein--findings in Alzheimer's and Niemann Pick C's disease[J]. Pharmacopsychiatry,2003,36(Suppl2):S120-S126.
[18] YAMAZAKI T,CHANG T Y,HAASS C,et al.Accumulation and aggregation of amyloid beta-protein in late endosomes of Niemann-pick type C cells[J].J Biol Chem,2001,276(6):4454-4460.
[19] YANG D S,STAVRIDES P,SAITO M,et al. Defective macroautophagic turnover of brain lipids in the Tg CRND8Alzheimer mouse model:prevention by correcting lysosomal proteolytic deficits[J]. Brain,2014,137(Pt 12):3300-3318.
[20] VAN ECHTEN-DECKERT G,WALTER J.Sphingolipids:critical players in Alzheimer's disease[J].Prog Lipid Res,2012,51(4):378-393.
[21] YAO J,HO D,CALINGASAN N Y,et al.Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease[J].J Exp Med,2012,209(13):2501-2513.
[22] YANG D S,STAVRIDES P,KUMAR A,et al.Cyclodextrin has conflicting actions on autophagy flux in vivo in brains of normal and Alzheimer model mice[J].Hum Mol Genet,2017,26(5):843-859.
[23] KNIGHT E M,WILLIAMS H N,STEVENS A C,et al.Evidence that small molecule enhancement of beta-hexosaminidase activity corrects the behavioral phenotype in Dutch APP(E693Q)mice through reduction of ganglioside-bound Abeta[J]. Mol Psychiatry,2015,20(1):109-117.
[24] RIVERS J R,MAGGO S D,ASHTON J C.Neuroprotective effect of hydroxypropyl-beta-cyclodextrin in hypoxia-ischemia[J].Neuroreport,2012,23(3):134-138.
[25] FRANK C,RUFINI S,TANCREDI V,et al. Cholesterol depletion inhibits synaptic transmission and synaptic plasticity in rat hippocampus[J].Exp Neurol,2008,212(2):407-414.
[26] SARI P,KERR D S. Domoic acid-induced hippocampal CA1 hyperexcitability independent of region CA3 activity[J].Epilepsy Res,2001,47(1-2):65-76.
[27] YURDAGUL A J R,FINNEY A C,WOOLARD M D,et al. The arterial microenvironment:the where and why of atherosclerosis[J]. Biochem J,2016,473(10):1281-1295.
[28] BACK M,HANSSON G K. Anti-inflammatory therapies for atherosclerosis[J].Nat Rev Cardiol,2015,12(4):199-211.
[29] LI H,EL-DAKDOUKI M H,ZHU D C,et al.Synthesis of beta-cyclodextrin conjugated superparamagnetic iron oxide nanoparticles for selective binding and detection of cholesterol crystals[J].Chem Commun(Camb),2012,48(28):3385-3387.
[30] ZIMMER S,GREBE A,BAKKE S S,et al. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming[J].Sci Transl Med,2016,8(333):333ra50.
[31] JEURISSEN M L J,WALENBERGH S M A,HOUBEN T,et al.Prevention of ox LDL uptake leads to decreased atherosclerosis in hematopoietic NPC1-deficient Ldlr(-/-)mice[J].Atherosclerosis,2016(255):59-65.
[32] DI MINNO G,SPADARELLA G,CAFARO G,et al.Systematic reviews and meta-analyses for more profitable strategies in peripheral artery disease[J]. Ann Med,2014,46(7):475-489.
[33] NORGREN L,HIATT W R,DORMANDY J A,et al.Inter-Society Consensus for the Management of Peripheral Arterial Disease(TASC II)[J]. J Vasc Surg,2007,45(Suppl S):S5-67.
[34] ZHAO Y,VANHOUTTE P M,LEUNG S W. Vascular nitric oxide:Beyond e NOS[J].J Pharmacol Sci,2015,129(2):83-94.
[35] QI X,YUAN Y,XU K,et al.(2-Hydroxypropyl)-betaCyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis[J]. PLoS One,2015,10(5):e0125323.
[36] MULAS M F,ABETE C,PULISCI D,et al.Cholesterol esters as growth regulators of lymphocytic leukaemia cells[J].Cell Prolif,2011,44(4):360-371.
[37] GEORGE K S,WU S.Lipid raft:A floating island of death or survival[J]. Toxicol Appl Pharmacol,2012,259(3):311-319.
[38] YAN J,LI Q F,WANG L S,et al. Methyl-betacyclodextrin induces programmed cell death in chronic myeloid leukemia cells and,combined with imatinib,produces a synergistic downregulation of ERK/SPK1signaling[J].Anticancer Drugs,2012,23(1):22-31.
[39] LOFTSSON T,BREWSTER M E.Pharmaceutical applications of cyclodextrins:basic science and product development[J].J Pharm Pharmacol,2010,62(11):1607-1621.
[40]YOKOO M,KUBOTA Y,MOTOYAMA K,et al. 2-Hydroxypropyl-beta-Cyclodextrin Acts as a Novel Anticancer Agent[J].PLoS One,2015,10(11):e0141946.