

浏览全部资源
扫码关注微信
1.贵州医科大学 附属医院,贵阳 550002
2.贵州省药品监督管理局 检查中心,贵阳 550081
3.贵州医科大学 药学院,贵阳 550004
Received:17 August 2020,
Published Online:20 January 2021,
Published:20 March 2021
移动端阅览
唐娟,刘琳,李承蔓等.羟基酪醇的药理作用和药代动力学研究进展[J].中国实验方剂学杂志,2021,27(06):241-250.
TANG Juan,LIU Lin,LI Cheng-man,et al.Research Progress on Pharmacological Action and Pharmacokinetics of Hydroxytyrosol[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(06):241-250.
唐娟,刘琳,李承蔓等.羟基酪醇的药理作用和药代动力学研究进展[J].中国实验方剂学杂志,2021,27(06):241-250. DOI: 10.13422/j.cnki.syfjx.20210317.
TANG Juan,LIU Lin,LI Cheng-man,et al.Research Progress on Pharmacological Action and Pharmacokinetics of Hydroxytyrosol[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(06):241-250. DOI: 10.13422/j.cnki.syfjx.20210317.
羟基酪醇(HT)是以酯类形式广泛存在于木犀科植物油橄榄的枝叶和果实中的多酚类化合物,是天然的抗氧化剂之一。近年来,大量研究发现,HT在代谢综合征、心血管疾病、神经退行性疾病等方面均有较好的活性,能够有效抗癌、抗炎、抗抑郁等;此外,HT属于亲水亲油性物质,具有较高的生物利用度和细胞毒性小的特点,能够快速分布于各组织器官且易透过血脑屏障。因此,研究人员将其视为新药开发的重点研究对象;但该药物在体内半衰期短,靶向性差,临床应用往往受到限制,仍需更深入的研究。笔者查阅了近年来国内外有关HT的报道,并对其基本性质、药理作用及作用机制、药代动力学进行归纳总结,着重介绍了HT的抗氧化应激损伤、缓解心血管疾病、抑制神经退行性疾病等的药理活性及作用机制,并对其抗炎、抗肿瘤、抗抑郁等生物活性以及体内药代动力学的现有研究进行简要综述,同时对其未来研究方向提出建议,以期为HT的进一步开发、研究和临床应用提供参考。
Hydroxytyrosol as one of natural anti-oxidants,extracted from the fruits and leaves of
Olea europaea
,is a natural polyphenol compound in the form of esters. Recently,considerable studies showed that hydroxytyrosol demonstrated intrinsic biological activity for metabolic syndromes, cardiovascular- and neurodegenerative-related diseases,and it was revealed to play the roles in the anti-activities of cancerous,inflammatory as well as depressing issues. In addition,hydroxytyrosol is an oleophilic and hydrophilic compound with high bioavailability and low cellular cytotoxicity. It could be absorbed by various tissues and could easily passe through blood brain barrier. Therefore,hydroxytyrosol was introduced as one of the key subjects targeted by innovative drug development. However,it has a short half-life
in
vivo
and non-tissue specific,which lead to its limitation in clinical application, so further in-depth studies are still needed. The authors had a literature review of hydroxytyrosol,and summarized the basic properties of its pharmacokinetic,pharmacological effects and molecular mechanisms. This article mainly focused on it’s pharmacological activity and the mechanism involved in treating damages induced by the oxidative stress,in alleviating cardiovascular diseases and in inhibition of neurodegenerative diseases. In this article, its anti-inflammatory,anti-tumor,anti-depressant effects,other biological activities,and pharmacokinetics were also briefly reviewed. The authors put forward some personal thoughts on its future research direction,hoping to provide ideas and inspirations for the vast number of researchers,and provide references for its further development,research and application.
KARKOVIĆ MARKOVIĆ A , TORIĆ J , BARBARIĆ M , et al . Hydroxytyrosol,tyrosol and derivatives and their potential effects on human health [J]. Molecules , 2019 , 24 ( 10 ): 2001 .
PARKINSON L , CICERALE S . The health benefiting mechanisms of virgin olive oil phenolic compounds [J]. Molecules , 2016 , 21 ( 12 ): 1734 .
MANNA C , GALLETTI P , MAISTO G , et al . Transport mechanism and metabolism of olive oil hydroxytyrosol in Caco-2 cells [J]. FEBS Lett , 2000 , 470 ( 3 ): 341 - 344 .
AUÑON-CALLES D , CANUT L , VISIOLI F . Toxicological evaluation of pure hydroxytyrosol [J]. Food Chem Toxicol , 2013 , 55 : 498 - 504 .
SONI M G , BURDOCK G A , CHRISTIAN M S , et al . Safety assessment of aqueous olive pulp extract as an antioxidant or antimicrobial agent in foods [J]. Food Chem Toxicol , 2006 , 44 ( 7 ): 903 - 915 .
NG S F , TAN L S , BUANG F . Transdermal anti-inflammatory activity of bilayer film containing olive compound hydroxytyrosol:physical assessment,in vivo dermal safety and efficacy study in Freund's adjuvant-induced arthritic rat model [J]. Drug Dev Ind Pharm , 2017 , 43 ( 1 ): 108 - 119 .
凌沛学 , 吴季栩 , 邵华荣 , 等 . 羟基酪醇及其衍生物在制备抗抑郁产品中的新应用 : 中国 , CN109223734A [P]. 2019-01-18 .
孙华庚 . 一种羟基酪醇微丸及其制备方法 : 中国 , CN102166195A [P]. 2011-08-31 .
於洪建 . 一种富含羟基酪醇、枸杞多糖和苹果多酚的用于保肝的胶囊和制剂 : 中国 , CN103550332A [P]. 2014-02-05 .
张亮 . 羟基酪醇嵌段共聚物纳米粒的制备及其评价研究 [D]. 哈尔滨 : 黑龙江中医药大学 , 2015 .
李欢欢 . 羟基酪醇前体药物的制备及体外活性评价 [D]. 唐山 : 华北理工大学 , 2016 .
DURACKOVÁ Z . Some current insights into oxidative stress [J]. Physiol Res , 2010 , 59 ( 4 ): 459 - 469 .
ANGELOVA P R , ABRAMOV A Y . Role of mitochondrial ROS in the brain: from physiology to neurodegeneration [J]. FEBS Lett , 2018 , 592 ( 5 ): 692 - 702 .
BERTELLI M , KIANI A K , PAOLACCI S , et al . Hydroxytyrosol:A natural compound with promising pharmacological activities [J]. J Biotechnol , 2020 , 309 : 29 - 33 .
KOUKA P , TSAKIRI G , TZORTZI D , et al . The polyphenolic composition of extracts derived from different greek extra virgin olive oils is correlated with their antioxidant potency [J]. Oxid Med Cell Longev , 2019 , 2019 : 1870965 .
SERVILI M , ESPOSTO S , FABIANI R , et al . Phenolic compounds in olive oil: antioxidant,health and organoleptic activities according to their chemical structure [J]. Inflammopharmacology , 2009 , 17 ( 2 ): 76 - 84 .
ZRELLI H , MATSUOKA M , KITAZAKI S , et al . Hydroxytyrosol induces proliferation and cytoprotection against oxidative injury in vascular endothelial cells: role of Nrf2 activation and HO-1 induction [J]. J Agric Food Chem , 2011 , 59 ( 9 ): 4473 - 4482 .
PENG S , ZHANG B , YAO J , et al . Dual protection of hydroxytyrosol,an olive oil polyphenol,against oxidative damage in PC12 cells [J]. Food Funct , 2015 , 6 ( 6 ): 2091 - 2100 .
UMENO A , TAKASHIMA M , MUROTOMI K , et al . Radical-scavenging activity and antioxidative effects of olive leaf components oleuropein and hydroxytyrosol in comparison with homovanillic alcohol [J]. J Oleo Sci , 2015 , 64 ( 7 ): 793 - 800 .
KITSATI N , MANTZARIS M D , GALARIS D . Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation [J]. Redox Biol , 2016 , 10 : 233 - 242 .
张书新 , 武宇超 . 羟基酪醇的研究进展 [J]. 中国卫生产业 , 2016 , 13 ( 19 ): 59 - 61 .
GHAFFARI M A , GHIASVAND T . Kinetic study of low density lipoprotein oxidation by copper [J]. Indian J Clin Biochem , 2010 , 25 ( 1 ): 29 - 36 .
BERROUGUI H , IKHLEF S , KHALIL A . Extra virgin olive oil polyphenols promote cholesterol efflux and improve hdl functionality [J]. Evid Based Complement Alternat Med , 2015 , 2015 : 208062 .
YU X H , FU Y C , ZHANG D W , et al . Foam cells in atherosclerosis [J]. Clin Chim Acta , 2013 , 424 : 245 - 252 .
HELAL O , BERROUGUI H , LOUED S , et al . Extra-virgin olive oil consumption improves the capacity of HDL to mediate cholesterol efflux and increases ABCA1 and ABCG1 expression in human macrophages [J]. Br J Nutr , 2013 , 109 ( 10 ): 1844 - 1855 .
DELL'AGLI M , FAGNANI R , MITRO N , et al . Minor components of olive oil modulate proatherogenic adhesion molecules involved in endothelial activation [J]. J Agric Food Chem , 2006 , 54 ( 9 ): 3259 - 3264 .
GONZÁLEZ-CORREA J A , NAVAS M D , MUÑOZ-MARÍN J , et al . Effects of hydroxytyrosol and hydroxytyrosol acetate administration to rats on platelet function compared to acetylsalicylic acid [J]. J Agric Food Chem , 2008 , 56 ( 17 ): 7872 - 7876 .
LANE C A , HARDY J , SCHOTT J M . Alzheimer's disease [J]. Eur J Neurol , 2018 , 25 ( 1 ): 59 - 70 .
SERRANO-POZO A , FROSCH M P , MASLIAH E , et al . Neuropathological alterations in Alzheimer disease [J]. Cold Spring Harb Perspect Med , 2011 , 1 ( 1 ): a006189
ARUNSUNDAR M , SHANMUGARAJAN T S , RAVICHANDRAN V . 3,4-Dihydroxyphenylethanol attenuates spatio-cognitive deficits in an Alzheimer’s disease mouse model: modulation of the molecular signals in neuronal survival-apoptotic programs [J]. Neurotox Res , 2015 , 27 ( 2 ): 143 - 155 .
ST-LAURENT-THIBAULT C , ARSENEAULT M , LONGPRÉ F , et al . Tyrosol and hydroxytyrosol,two main components of olive oil,protect N2a cells against amyloid- β -induced toxicity.Involvement of the NF- κ B signaling [J]. Curr Alzheimer Res , 2011 , 8 ( 5 ): 543 - 551 .
ZHENG A , LI H , CAO K , et al . Maternal hydroxytyrosol administration improves neurogenesis and cognitive function in prenatally stressed offspring [J]. J Nutr Biochem , 2015 , 26 ( 2 ): 190 - 199 .
TORRE L A , SIEGEL R L , WARD E M , et al . Global cancer incidence and mortality rates and trends-an update [J]. Cancer Epidemiol Biomarkers Prev , 2016 , 25 ( 1 ): 16 - 27 .
HAN J , TALORETE TP , YAMADA P , et al . Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells [J]. Cytotechnology , 2009 , 59 ( 1 ): 45 - 53 .
ZHANG X M , CAO J , JIANG L , et al . Protective effect of hydroxytyrosol against acrylamide-induced cytotoxicity and DNA damage in HepG2 cells [J]. Mutat Res , 2009 , 664 ( 1 ): 64 - 68 .
TOTEDA G , LUPINACCI S , VIZZA D , et al . High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells [J]. J Endocrinol Invest , 2017 , 40 ( 2 ): 153 - 162 .
BAGETTA D , MARUCA A , LUPIA A , et al . Mediterranean products as promising source of multi-target agents in the treatment of metabolic syndrome [J]. Eur J Med Chem , 2020 , 186 : 111903 .
FKI I , SAYADI S , MAHMOUDI A , et al . Comparative study on beneficial effects of hydroxytyrosol- and oleuropein-rich olive leaf extracts on high-fat diet-induced lipid metabolism disturbance and liver injury in rats [J]. BioMed Res Int , 2020 , 2020 : 1315202 .
LUTFI E , BABIN P J , GUTIÉRREZ J , et al . Caffeic acid and hydroxytyrosol have anti-obesogenic properties in zebrafish and rainbow trout models [J]. PLoS One , 2017 , 12 ( 6 ): e0178833 .
DRIRA R , CHEN S , SAKAMOTO K . Oleuropein and hydroxytyrosol inhibit adipocyte differentiation in 3 T3-L1 cells [J]. Life Sci , 2011 , 89 ( 19 ): 708 - 716 .
RICHARD N , ARNOLD S , HOELLER U , et al . Hydroxytyrosol is the major anti-inflammatory compound in aqueous olive extracts and impairs cytokine and chemokine production in macrophages [J]. Planta Med , 2011 , 77 ( 17 ): 1890 - 1897 .
ZHANG X , CAO J , ZHONG L . Hydroxytyrosol inhibits pro-inflammatory cytokines,iNOS,and COX-2 expression in human monocytic cells [J]. Naunyn Schmiedebergs Arch Pharmacol , 2009 , 379 ( 6 ): 581 - 586 .
CHIN K Y , IMA-NIRWANA S . Olives and bone:a green osteoporosis prevention option [J]. Int J Environ Res Public Health , 2016 , 13 ( 8 ): 1 - 11 .
FACCHINI A , CETRULLO S , D'ADAMO S , et al . Hydroxytyrosol prevents increase of osteoarthritis markers in human chondrocytes treated with hydrogen peroxide or growth-related oncogene α [J]. PLoS One , 2014 , 9 ( 10 ): e109724 .
HAGIWARA K , GOTO T , ARAKI M , et al . Olive polyphenol hydroxytyrosol prevents bone loss [J]. Eur J Pharmacol , 2011 , 662 ( 1-3 ): 78 - 84 .
LIU Z , SUN L , ZHU L , et al . Hydroxytyrosol protects retinal pigment epithelial cells from acrolein-induced oxidative stress and mitochondrial dysfunction [J]. J Neurochem , 2007 , 103 ( 6 ): 2690 - 2700 .
ZOU X , FENG Z , LI Y , et al . Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells:activation of Nrf2 and JNK-p62/SQSTM1 pathways [J]. J Nutr Biochem , 2012 , 23 ( 8 ): 994 - 1006 .
ZHU L , LIU Z , FENG Z , et al . Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase Ⅱ detoxifying enzyme systems in retinal pigment epithelial cells [J]. J Nutr Biochem , 2010 , 21 ( 11 ): 1089 - 1098 .
陈倩 . 羟基酪醇调控自噬缓解毛乳头细胞氧化应激损伤机制研究 [D]. 广州 : 南方医科大学 , 2019 .
申玲 , 张璐璐 , 陈赛娇 , 等 . 羟基酪醇对小鼠抑郁样行为的改善作用及机制研究 [J]. 营养学报 , 2020 , 42 ( 4 ): 1 - 6 .
LEE-HUANG S , HUANG P L , ZHANG D , et al . Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: part Ⅱ. integrase inhibition [J]. Biochem Biophys Res Commun , 2007 , 354 ( 4 ): 879 - 884 .
BEDOYA L M , BELTRÁN M , OBREGÓN-CALDERÓN P , et al . Hydroxytyrosol:a new class of microbicide displaying broad anti-HIV-1 activity [J]. AIDS , 2016 , 30 ( 18 ): 2767 - 2776 .
VILAPLANA-PÉREZ C , AUÑÓN D , GARCÍA-FLORES L A , et al . Hydroxytyrosol and potential uses in cardiovascular diseases,cancer,and AIDS [J]. Front Nutr , 2014 , 1 : 18 .
VISSERS M N , ZOCK P L , ROODENBURG A J , et al . Olive Oil Phenols Are Absorbed in Humans [J]. J Nutr , 2002 , 132 ( 3 ): 409 - 417 .
TUCK K L , FREEMAN M P , HAYBALL P J , et al . The in vivo fate of hydroxytyrosol and tyrosol,antioxidant phenolic constituents of olive oil,after intravenous and oral dosing of labeled compounds to rats [J]. J Nutr , 2001 , 131 ( 7 ): 1993 - 1996 .
GONZÁLEZ-SANTIAGO M , FONOLLÁ J , LOPEZ-HUERTAS E . Human absorption of a supplement containing purified hydroxytyrosol,a natural antioxidant from olive oil,and evidence for its transient association with low-density lipoproteins [J]. Pharmacol Res , 2010 , 61 ( 4 ): 364 - 370 .
D′ANGELO S , MANNA C , MIGLIARDI V , et al . Pharmacokinetics and metabolism of hydroxytyrosol,a natural antioxidant from olive oil [J]. Drug Metab Dispos , 2001 , 29 ( 11 ): 1492 - 1498 .
SERRA A , RUBIÓ L , BORRÀS X , et al . Distribution of olive oil phenolic compounds in rat tissues after administration of a phenolic extract from olive cake [J]. Mol Nutr Food Res , 2012 , 56 ( 3 ): 486 - 496 .
RUBIÓ L , VALLS R M , MACIÀ A , et al . Impact of olive oil phenolic concentration on human plasmatic phenolic metabolites [J]. Food Chem , 2012 , 135 ( 4 ): 2922 - 2929 .
MIRO CASAS E , COVAS M I , FARRE M , et al . Hydroxytyrosol disposition in humans [J]. Clin Chem , 2003 , 49 ( 6 ): 945 - 952 .
VISIOLI F , GALLI C , BORNET F , et al . Olive oil phenolics are dose-dependently absorbed in humans [J]. FEBS Lett , 2000 , 468 ( 2/3 ): 159 - 160 .
崔月莉 , 张丹捷 , 栾茹乔 , 等 . 高效液相色谱-荧光检测法测定大鼠血浆中羟基酪醇及其药动学研究 [J]. 时珍国医国药 , 2019 , 30 ( 10 ): 2324 - 2326 .
徐保鑫 , 李转梅 , 张学兰 , 等 . 女贞子中橄榄苦苷与羟基酪醇在大鼠血浆中的药动学差异 [J]. 中成药 , 2017 , 39 ( 7 ): 1387 - 1390 .
YUAN J J , QIN FGF , TU J L , et al . Preparation,characterization,and antioxidant activity evaluation of liposomes containing water-soluble hydroxytyrosol from olive [J]. Molecules , 2017 , 22 ( 6 ): 870 .
OBACH R S , BAXTER J G , LISTON T E , et al . The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data [J]. J Pharmacol Exp Ther , 1997 , 283 ( 1 ): 46 - 58 .
赵冬梅 , 李燕 , 卢业竑 . 药物代谢研究在新药开发中的作用 [J]. 药学学报 , 2000 , 35 ( 2 ): 156 - 160 .
巩仔鹏 , 陈颖 , 张瑞杰 , 等 . 疾病状态下的中药药代动力学研究进展 [J]. 中国中药杂志 , 2015 , 40 ( 2 ): 169 - 173 .
0
Views
18
下载量
6
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621