左 丹,廖 霞,李 瑤,石 芳,王麗穎,明 建,2,*
(1.西南大學(xué)食品科學(xué)學(xué)院,重慶 400715;2.重慶市特色食品工程技術(shù)研究中心,重慶 400715)
基于腸道吸收機(jī)制的膳食多酚代謝研究進(jìn)展
左 丹1,廖 霞1,李 瑤1,石 芳1,王麗穎1,明 建1,2,*
(1.西南大學(xué)食品科學(xué)學(xué)院,重慶 400715;2.重慶市特色食品工程技術(shù)研究中心,重慶 400715)
膳食多酚是植物性食物的重要成分,不僅與食品的風(fēng)味和顏色等品質(zhì)直接相關(guān),還有利于人體健康。由于它們?cè)诨|(zhì)釋放、消化、吸收、代謝和組織分布期間發(fā)生改變,使得各種酚類化合物生物利用度有一定的差異。飲食中含量最豐富的不一定具有最佳生物利用度,多酚的吸收轉(zhuǎn)化及生物利用度是多酚生物活性主要研究熱點(diǎn)之一。本文以多酚腸道吸收機(jī)制為基點(diǎn),綜述了膳食多酚在胃腸道釋放、吸收、代謝等過(guò)程,以期為多酚類保健食品的研發(fā)提供依據(jù)。
膳食多酚;生物利用度;吸收;代謝;轉(zhuǎn)運(yùn)
多酚是植物體內(nèi)復(fù)雜酚類次生代謝產(chǎn)物,由一個(gè)或多個(gè)芳環(huán)化合物與一個(gè)或多個(gè)羥基組成,主要包括酚酸、類黃酮、對(duì)二苯代乙烯、香豆素、單寧等。具有抗氧化、抗癌、降血壓、降血糖、抗菌等多方面保健和藥理作用[1]。膳食多酚主要來(lái)源于水果、蔬菜和飲料,每100 g新鮮果蔬中含有200~300 mg多酚類化合物[2]。成年人通過(guò)膳食攝入多酚類化合物的總量約為(1 193±510) mg/d[3]。
盡管多酚在膳食中含量很高,但它們?cè)隗w內(nèi)的生物利用度較差。由于膳食多酚多以糖基化或酯類、聚合物形式存在于植物性食物中,吸收前需經(jīng)過(guò)腸道酶(如乳糖酶-根皮苷水解酶(lactase-phlorizin hydrolase,LPH))或微生物菌群水解,然后在細(xì)胞色素P450家族(cytochromes P450,CYPs)、兒茶酚-O-甲基轉(zhuǎn)移酶(catechol-O-methyltransferase,COMT)、硫酸基轉(zhuǎn)移酶(sulfotransferase,SULTs)、葡萄糖醛酸轉(zhuǎn)移酶(UDP-glucuronosyltransferases,UGTs)等代謝酶作用下進(jìn)行廣泛代謝,改變其原本的結(jié)構(gòu),之后一部分多酚進(jìn)入血液循環(huán),一部分被腸道外排轉(zhuǎn)運(yùn)體如P-糖蛋白(P-glycoprotein,P-gp)、多藥耐藥相關(guān)蛋白2(multidrug resistance-associated protein 2,MRP2)、乳腺癌耐藥蛋白(breast cancer resistance protein,BCRP)等外排回腸腔,導(dǎo)致生物利用度降低(圖1)。
圖1 膳食多酚在腸道中釋放和吸收過(guò)程示意圖[4]Fig. 1 Schematic diagram for the process of intestinal release and absorption of dietary polyphenols[4]
本文以多酚腸道吸收機(jī)制為基點(diǎn),綜述膳食多酚在胃腸道釋放、吸收、代謝等體內(nèi)過(guò)程,以期為多酚類保健食品的研發(fā)提供依據(jù)。
多酚在胃腸消化期間從食物基質(zhì)中逐漸完全釋放出來(lái),生物有效性增加,可用于吸收或在胃腸道中發(fā)揮其生物學(xué)效應(yīng)[5]。釋放水平主要由多酚結(jié)構(gòu)和腸道菌群的差異決定。
1.1 胃中釋放
大多數(shù)多酚在胃消化期間被釋放,主要由胃消化酶介導(dǎo)。如低聚合單寧(單體,二聚體和三聚體)與唾液蛋白形成的復(fù)合物可以通過(guò)胃消化被破壞,導(dǎo)致單寧釋放,相反單寧四聚體和五聚體形成的復(fù)合物耐胃消化更顯著[6]。如蘋(píng)果中65%的多酚和黃酮類化合物在胃中釋放,小腸中釋放量小于10%[7]。
酸性條件下,一些多酚可以在唾液亞硝酸鹽作用下在胃中被釋放。如槲皮素、山奈酚、花青素、兒茶素類、咖啡酸、綠原酸、3,4,5-三羥基苯甲酸等均能被亞硝酸鹽氧化[8-9]。Hirota等[10]發(fā)現(xiàn)亞硝酸鹽能與蘋(píng)果甲醇提取物在酸性緩沖溶液(pH 2.0)和酸化唾液中反應(yīng),反應(yīng)速率依次為綠原酸<(-)-表兒茶素<原花青素B2。
1.2 小腸中釋放
一些多酚在小腸溫和堿性條件下高度敏感,且在弱堿性條件下胰腺和膽汁分泌的一些酶(如淀粉酶、胰蛋白酶、胰凝乳蛋白酶原等)被激活,使這些多酚能以良好的比例轉(zhuǎn)化為具有不同化學(xué)性質(zhì)的其他未知結(jié)構(gòu)形式,從而具有不同的生物利用度和生物活性[11]。Bermúdez-Soto等[12]研究野櫻桃汁酚類成分時(shí)發(fā)現(xiàn)胃消化對(duì)其酚類成分(花青素、黃烷-3-醇、黃酮醇和咖啡酸衍生物)沒(méi)有實(shí)質(zhì)性影響,而在胰酶消化過(guò)程中有明顯改變。用胰酶處理2 h約釋放43%,黃酮醇和黃烷-3-醇含量分別下降26%和19%,新綠原酸含量下降28%,綠原酸含量提高24%。此外,位于小腸黏膜上皮細(xì)胞刷狀緣上的糖苷酶如LPH能催化糖基釋放苷元 。
1.3 結(jié)腸中釋放
膳食中不可萃取多酚在口腔、胃、小腸作用下不能從食品基質(zhì)中被釋放,到達(dá)結(jié)腸后,在腸道菌群酶作用下糖苷鍵斷裂形成苷元或進(jìn)一步發(fā)生環(huán)裂解產(chǎn)生酚酸,被吸收或排泄[13]。釋放機(jī)制有兩種,一是與糖、有機(jī)酸、脂類等酯化的酚類在結(jié)腸菌群產(chǎn)生的酯酶作用下斷裂酯鍵。二是鞣花單寧等聚合物則需微生物裂解其共軛基團(tuán)。據(jù)估計(jì),48%的膳食多酚在小腸變得生物可接受,其余52%在大腸[14]。
只有少量的腸道微生物(如大腸桿菌、雙歧桿菌、乳桿菌、真桿菌等)能將膳食多酚進(jìn)行生物轉(zhuǎn)化[15]。產(chǎn)物主要是苯乙酸和苯丙酸或其羥基化合物,酚酸經(jīng)腸道直接吸收或與腸道細(xì)胞表面特定或非特定受體結(jié)合,通過(guò)影響多個(gè)基因的表達(dá)和信號(hào)轉(zhuǎn)導(dǎo)發(fā)揮生理功能[16]。Kubow等[17]研究發(fā)現(xiàn)紫肉甘薯中花色素苷降解和生物有效性依賴于結(jié)腸微生物的分解。Padayachee等[18]研究發(fā)現(xiàn)果蔬中與胞壁結(jié)合的多酚在結(jié)腸中通過(guò)細(xì)胞壁降解菌作用而被釋放。
1.4 影響多酚釋放的主要因素
胃腸道pH值。多酚在消化過(guò)程中降解和活性下降主要是由pH值變化引起的[19]。如兒茶素在模擬酸性胃環(huán)境中較穩(wěn)定,在近中性或堿性環(huán)境下大幅度降解,兒茶素類衍生物的降解大多發(fā)生在小腸環(huán)境,在腸液環(huán)境的損失量通常比胃環(huán)境高10~20 倍[20]。胃消化過(guò)程中總酚、黃酮類和花青素類的生物可及性增加,而在腸道環(huán)境中酚酸和白藜蘆醇降解,兒茶素、槲皮素則相對(duì)較穩(wěn)定[21]。
與其他營(yíng)養(yǎng)物質(zhì)相互作用。膳食多酚能與食品基質(zhì)的某些成分,如蛋白質(zhì)、鐵、膳食纖維相互作用,形成復(fù)合物,變得不可吸收,影響其生物有效性,但這種相互作用能被消化酶或微生物破壞[22]。Mosele等[23]研究發(fā)現(xiàn)果膠的存在會(huì)阻礙酚類化合物的溶解,腸消化過(guò)程中果膠的降解有利于酚類化合物的釋放。
2.1 吸收部位
膳食多酚攝入后,一部分先在胃部被低程度吸收,如黃酮醇(槲皮素)、異黃酮苷元(大豆素和染料木素)、花色苷、酚酸(阿魏酸、咖啡酸、綠原酸、沒(méi)食子酸),主要是單酚酸類物質(zhì)[24]。只有少部分多酚(5%~10%)在小腸吸收(主要是游離態(tài)多酚),其余未被吸收多酚(主要是結(jié)合態(tài)多酚)到達(dá)結(jié)腸,在腸中微生物菌群作用下進(jìn)行分解、釋放、吸收[25]。
2.2 吸收機(jī)制
影響膳食多酚腸道吸收機(jī)制的因素很多,如烷基鏈長(zhǎng)、羥基取代、化學(xué)結(jié)構(gòu)、分子質(zhì)量等。小分子多酚如沒(méi)食子酸、異黃酮、兒茶素等很容易通過(guò)腸道吸收,大分子多酚如花青素吸收較差[26]。腸道主要通過(guò)主動(dòng)轉(zhuǎn)運(yùn)和被動(dòng)擴(kuò)散兩種機(jī)制來(lái)吸收多酚,以被動(dòng)擴(kuò)散為主。
2.2.1 主動(dòng)運(yùn)輸
主動(dòng)運(yùn)輸是指物質(zhì)逆濃度梯度運(yùn)輸,由細(xì)胞膜上轉(zhuǎn)運(yùn)蛋白介導(dǎo)。與相應(yīng)苷元相比,酚苷類物質(zhì)親水性較好,很難通過(guò)被動(dòng)擴(kuò)散跨過(guò)腸上皮細(xì)胞膜,主要通過(guò)主動(dòng)運(yùn)輸[27]。主要包括Na+依賴的主動(dòng)轉(zhuǎn)運(yùn)和MCT介導(dǎo)的主動(dòng)轉(zhuǎn)運(yùn)兩種方式。糖苷被載體運(yùn)輸?shù)缴掀ぜ?xì)胞內(nèi),由細(xì)胞內(nèi)β-葡萄糖苷酶(cytosolic β-glucosidase,CBG)介導(dǎo)其水解。大量研究證實(shí),SGLT-1參與肉桂酸、綠原酸、阿魏酸、咖啡酸、槲皮素-4-葡萄糖苷、大黃素和白藜蘆醇等轉(zhuǎn)運(yùn)過(guò)程[28]。此外,易化性葡萄糖轉(zhuǎn)運(yùn)載體-2(facilitated glucose transporter-2,GLUT-2)也參與一些膳食多酚的轉(zhuǎn)運(yùn)[29]。李素云[30]研究表明SGLT-1是槲皮素及其兩個(gè)糖苷(槲皮苷和異槲皮苷)在腸道吸收中的轉(zhuǎn)運(yùn)蛋白之一,同時(shí)槲皮苷也通過(guò)GLUT-2轉(zhuǎn)運(yùn)吸收。
MCT的底物是含有陰離子羧酸基團(tuán)、非極性側(cè)鏈或芳香族疏水性基團(tuán)的酚類物質(zhì),如咖啡酸、阿魏酸、表兒茶素沒(méi)食子酸,主要為單羧酸類物質(zhì)。Dang Yunjie等[31]研究證實(shí)MCT參與了菠蘿葉提取物(extract of Ananas comosus L. leaves,EAL)中p-香豆酸和咖啡酸的跨膜轉(zhuǎn)運(yùn),兩種物質(zhì)的滲透具有濃度和時(shí)間依賴性。關(guān)于哪些MCT參與多酚的轉(zhuǎn)運(yùn)仍未明確,除已報(bào)道的MCT3、MCT4、MCT5、MCT6外,還有一些多酚的相關(guān)轉(zhuǎn)運(yùn)蛋白[4]。
2.2.2 被動(dòng)擴(kuò)散
多酚被消化后釋放的苷元主要通過(guò)被動(dòng)擴(kuò)散進(jìn)入腸上皮細(xì)胞。被動(dòng)擴(kuò)散是由濃度梯度驅(qū)使,有跨細(xì)胞途徑(通過(guò)腸上皮細(xì)胞膜進(jìn)入血液)或者細(xì)胞旁路途徑(通過(guò)腸上皮細(xì)胞間的緊密聯(lián)接進(jìn)入血液)兩種途徑,取決于物質(zhì)的疏水性。含羥基較多的多酚親水性好,它們會(huì)通過(guò)細(xì)胞旁路途徑被優(yōu)先吸收,如(+)-兒茶素、(-)-表兒茶素、原花青素B2等[32]。山楂樹(shù)葉和花中原花色素可通過(guò)跨細(xì)胞途徑和細(xì)胞旁路途徑被吸收,原花青素B2和聚合度4~6的原花青素滲透率都很低,分子質(zhì)量越大滲透性越差[33],Rastogi等[34]研究發(fā)現(xiàn)6 種酚類化合物(白楊素、咖啡酸、沒(méi)食子酸、槲皮素、白藜蘆醇、蘆?。┩ㄟ^(guò)Caco-2細(xì)胞吸收低且在人工膜滲透性(parallel artif i cial membrane permeability assay,PAMPA)差,其跨膜運(yùn)輸主要是通過(guò)被動(dòng)擴(kuò)散。Kimura等[35]也證實(shí)川陳皮素(nobiletin,NBL)在Caco-2細(xì)胞頂膜的吸收主要是由被動(dòng)擴(kuò)散過(guò)程介導(dǎo)。
此外,兩種方式也可同時(shí)參與膳食多酚的吸收。如白藜蘆醇被血管內(nèi)皮細(xì)胞吸收是由被動(dòng)擴(kuò)散和SGLT-1介導(dǎo)的過(guò)程[36]。Konishi[37]研究發(fā)現(xiàn)槲皮素3種代謝產(chǎn)物中,3,4-二羥基苯乙酸(3,4-dihydroxyphenylacetic acid,DHPA)通過(guò)細(xì)胞旁路途徑運(yùn)輸,4-羥基-3-甲氧基苯基乙酸(4-hydroxy-3-methoxyphenylacetic acid,HMPA)和間-羥基苯乙酸(m-hydroxyphenylacetic acid,mHPA)的吸收由MCT介導(dǎo)。
膳食多酚吸收后進(jìn)入血液循環(huán)之前,會(huì)受到Ⅰ相和Ⅱ相代謝酶作用,一部分進(jìn)入血液循環(huán),另一部分被外排轉(zhuǎn)運(yùn)體泵回腸腔。大量研究表明,許多代謝物比它們的前體具有更活躍的生物功能[38]。
3.1 Ⅰ相代謝
Ⅰ相代謝反應(yīng)有氧化反應(yīng)、還原反應(yīng)和水解反應(yīng),反應(yīng)使分子結(jié)構(gòu)中引入或暴露出極性基團(tuán),如產(chǎn)生羥基、羧基、巰基、氨基等。多種酶參與Ⅰ相代謝反應(yīng),包括還原酶、酯酶、CYPs等。CYPs是人體內(nèi)最重要的Ⅰ相代謝酶系,其中CYP1、CYP2、CYP3家族負(fù)責(zé)外源性物質(zhì)的代謝。在腸吸收中,50%以上藥物的Ⅰ相代謝與CYP3A4相關(guān)[39]。
作為一種單加氧酶,CYPs可參與多種催化氧化反應(yīng),引入極性基團(tuán)(如羥基),增加物質(zhì)親水性,有助于Ⅱ相結(jié)合酶的利用或排泄[40]。如染料木黃酮和NBL容易被CYPs氧化[41]。此外,膳食多酚可與CYPs相互作用或影響CYPs基因表達(dá)而改變CYPs活性[42]。
3.2 Ⅱ相代謝
Ⅱ相代謝是結(jié)合反應(yīng),通常是藥物或Ⅰ相反應(yīng)生成的代謝產(chǎn)物結(jié)構(gòu)中的極性官能團(tuán)(如羥基、氨基、硝基和羧基等)與機(jī)體內(nèi)源性物質(zhì)發(fā)生偶聯(lián)或結(jié)合生成各種結(jié)合物的過(guò)程。由于膳食多酚類結(jié)構(gòu)使他們不適于細(xì)胞色素P450基板,大多數(shù)膳食多酚不進(jìn)行Ⅰ相代謝,可直接進(jìn)行Ⅱ相代謝,主要包括甲基化、硫酸鹽化和葡糖醛酸化,并通過(guò)增加其親水性促進(jìn)在膽汁和尿中消除[43]。Ⅱ相代謝發(fā)生部位主要是腸和肝。del Rio等[44]報(bào)道漿果中酚類化合物的吸收形式是以葡萄糖苷、硫酸酯和甲基化產(chǎn)物從胃腸道進(jìn)入循環(huán)系統(tǒng)。
甲基化反應(yīng)由COMT介導(dǎo),它能催化S-腺苷-L-甲硫氨酸的甲基轉(zhuǎn)移至有鄰苯二酚結(jié)構(gòu)的多酚,如槲皮素、兒茶素、咖啡酸、木犀草素、花青素等。反應(yīng)主要發(fā)生在多酚的C3’位,但也有一小部分形成4’-O-甲基化產(chǎn)物[45]。SULTs催化硫酸基團(tuán)從3’-磷酸腺苷-5’-磷酸硫酸轉(zhuǎn)移到多酚的C3’、C4’、C5、C7位羥基上[46]。UGTs催化葡萄糖醛酸從UDP-葡萄糖醛酸轉(zhuǎn)移至多酚的C7位、C4’位羥基上,C7位最易發(fā)生,而C5位幾乎不發(fā)生葡萄糖醛酸化[47]。Chen Jun等[48]研究6 種異黃酮(染料木黃酮、黃豆苷元、黃豆黃素、芒柄花素、鷹嘴豆素A和櫻黃素)在Caco-2細(xì)胞單層上的吸收代謝,發(fā)現(xiàn)櫻黃素主要被硫酸鹽化,另外5 種異黃酮被葡萄糖醛酸化,C7是葡萄糖醛酸化的主要位點(diǎn),C4’是硫酸鹽化的唯一位點(diǎn)。
3 種類型變化形式的重要性取決于底物性質(zhì)和攝入劑量,化合物結(jié)構(gòu)中細(xì)小差別將對(duì)其代謝通路產(chǎn)生顯著性影響[49]。如大鼠靜脈注射多酚劑量增加時(shí),硫酸鹽化作用明顯轉(zhuǎn)變?yōu)槠咸讶┧峄痆50]。騰增輝[51]研究發(fā)現(xiàn)芹菜素、白藜蘆醇、大黃酚和大黃素在腸道Ⅱ相代謝酶的作用下,易生成葡萄糖醛酸化和硫酸酯化代謝物,Caco-2細(xì)胞中大黃素和大黃酚與腸道UGTs的親和力更高,容易生成葡萄糖醛酸化代謝產(chǎn)物,遠(yuǎn)多于硫酸酯化的代謝產(chǎn)物;而Caco-2細(xì)胞中芹菜素和白藜蘆醇對(duì)SULT亦具有較高的親和力,葡萄糖醛酸化與硫酸酯化代謝產(chǎn)物之間的量差別不大。
廣泛分布于腸上皮細(xì)胞黏膜的腸道外排轉(zhuǎn)運(yùn)體可以將吸收后的部分多酚泵出細(xì)胞膜外,也可與代謝酶發(fā)生協(xié)同作用,阻止膳食多酚的吸收,這是多酚生物利用度較低的重要原因。主要有3 種ATP-依賴性外排轉(zhuǎn)運(yùn)體(ATP-binding cassette (ABC) transporter),即P-gp、MRP2、BCRP,它們能依賴ATP分解釋放的能量將底物外排回腸腔。大部分P-gp底物是結(jié)構(gòu)和藥理活性不相關(guān)的疏水、親脂性、中性或弱堿性化合物[52]。MRP2主要是有機(jī)陰離子的載體如谷胱甘肽結(jié)合物、葡萄糖醛酸結(jié)合物、硫酸結(jié)合物等。不同的是,MRP1、MRP3、MRP4、MRP5等能將多酚運(yùn)輸至血液,對(duì)多酚的吸收有促進(jìn)作用。BCRP屬于半ABC轉(zhuǎn)運(yùn)體,要形成同型二聚體后才可發(fā)揮轉(zhuǎn)運(yùn)的功能。
3 種外排轉(zhuǎn)運(yùn)體的底物不完全相同但有交叉。有研究發(fā)現(xiàn)轉(zhuǎn)運(yùn)體P-gp對(duì)燈盞花素吸收基本無(wú)影響,MRP2可將吸收的燈盞花素從腸上皮細(xì)胞內(nèi)又轉(zhuǎn)運(yùn)回腸腔,從而降低其吸收[53]。何卉等[54]研究發(fā)現(xiàn)白藜蘆醇及白藜蘆醇苷具有抑制P-gp外排的作用,但其本身不被P-gp外排,而是被MRP2外排。王婷婷等[55]研究發(fā)現(xiàn)P-gp與BCRP外排作用是田薊苷小腸吸收的主要外排機(jī)制,能夠依賴SGLT-1實(shí)現(xiàn)在小腸的吸收轉(zhuǎn)運(yùn)。
最后剩余的多酚代謝衍生物通過(guò)門靜脈進(jìn)入血液到達(dá)肝臟發(fā)生更多Ⅱ相代謝,其中部分代謝物通過(guò)膽汁分泌系統(tǒng)再次進(jìn)入腸道,經(jīng)腸道微生物酶代謝后重新被吸收,其余的共軛代謝物再次進(jìn)入血液分布到其他組織,最終通過(guò)尿或糞便排泄[56]。
大多數(shù)膳食多酚以糖基化或酯類、聚合物形式存在于植物性食物中,必須經(jīng)過(guò)腸道酶或微生物菌群水解,釋放酚苷元才能被吸收。在吸收過(guò)程中,膳食多酚先后在腸和肝臟中代謝,主要包括甲基化、硫酸化、葡萄糖醛酸化。吸收后一部分多酚進(jìn)入血液循環(huán),一部分被外排回腸腔。酚類化合物的母核結(jié)構(gòu)以及羥基的數(shù)目和位置影響它們與代謝酶以及藥物轉(zhuǎn)運(yùn)載體的親和力,在胃腸道體現(xiàn)不同的吸收特性,最終影響膳食多酚的生理效應(yīng)和功能活性。
多酚有效成分在體內(nèi)生物效應(yīng)多表現(xiàn)為高代謝和弱生物利用度,這是多酚作為藥物或保健食品開(kāi)發(fā)應(yīng)用的障礙和限制。未來(lái)在以下幾點(diǎn)需要有更全面的研究。一是多酚體內(nèi)藥動(dòng)學(xué)過(guò)程,許多膳食多酚的生物轉(zhuǎn)化和生物利用度仍不清楚,如關(guān)于膳食多酚在人體內(nèi)胃腸道吸收、組織分布和生物轉(zhuǎn)化途徑等關(guān)鍵問(wèn)題的數(shù)據(jù)需要被確定;二是膳食多酚代謝物的生物活性需要科學(xué)評(píng)價(jià);三是如何提高多酚的生物利用度。
[1] ANCILLOTTI C, CIOFI L, PUCCI D, et al. Polyphenolic prof i les and antioxidant and antiradical activity of Italian berries from Vaccinium myrtillus L. and Vaccinium uliginosum L. subsp. gaultherioides (Bigelow) S.B. Young[J]. Food Chemistry, 2016, 204: 176-184. DOI:10.1016/j.foodchem.2016.02.106.
[2] SCALBERT A, MANACH C, MORAND C, et al. Dietary polyphenols and the prevention of diseases[J]. Critical Reviews in Food Science and Nutrition, 2005, 45(4): 287-306. DOI:10.1080/1040869059096.
[3] PéREZ-JIMéNEZ J, FEZEU L, TOUVIER M, et al. Dietary intake of 337 polyphenols in French adults[J]. American Journal of Clinical Nutrition, 2011, 93(6): 1220-1228. DOI:10.3945/ajcn.110.007096.
[4] BOHN T. Dietary factors affecting polyphenol bioavailability[J]. Nutrition Reviews, 2014, 72(7): 429-452. DOI:10.1111/nure.12114.
[5] SANZ-BUENHOMBRE M, VILLANUEVA S, MORO C, et al. Bioavailability and the mechanism of action of a grape extract rich in polyphenols in cholesterol homeostasis[J]. Journal of Functional Foods, 2016, 21: 178-185. DOI:10.1016/j.jff.2015.11.044.
[6] SOARES S, BRAND?O E, MATEUS N, et al. Interaction between red wine procyanidins and salivary proteins: effect of stomach digestion on the resulting complexes[J]. RSC Advances, 2015, 5(17): 12664-12670. DOI:10.1039/c4ra13403f.
[7] BOUAYED J, HOFFMANN L, BOHN T. Total phenolics, fl avonoids, anthocyanins and antioxidant activity following simulated gastrointestinal digestion and dialysis of apple varieties: bioaccessibility and potential uptake[J]. Food Chemistry, 2011, 128(1): 14-21. DOI:10.1016/j.foodchem.2011.02.052.
[8] GAGO B, LUNDBERG J O, BARBOSA R M, et al. Red winedependent reduction of nitrite to nitric oxide in the stomach[J]. Free Radical Biology and Medicine, 2007, 43(9): 1233-1242. DOI:10.1016/ j.freeradbiomed.2007.06.007.
[9] TAKAHAMA U, YAMAUCHI R, HIROTA S. Reactions of (+)-catechin with salivary nitrite and thiocyanate under conditions simulating the gastric lumen: production of dinitrosocatechin and its thiocyanate conjugate[J]. Free Radical Research, 2014, 48(8): 965-966. DOI:10.3109/10715762.2014.929121.
[10] HIROTA S, TAKAHAMA U. Reactions of apple fruit polyphenols with nitrite under conditions of the gastric lumen: generation of nitric oxide and formation of nitrosocatechins[J]. Food Science and Technology Research, 2014, 20(2): 439-447. DOI:10.3136/fstr.20.439.
[11] VELDERRAIN-RODRíGUEZ G R, PALAFOX-CARLOS H, WALLMEDRANO A, et al. Phenolic compounds: their journey after intake[J]. Food and Function, 2014, 5(2): 189-197. DOI:10.1039/c3fo60361j.
[12] BERMúDEZ-SOTO M J, TOMáS-BARBERáN F A, GARCíACONESA M T. Stability of polyphenols in chokeberry (Aronia melanocarpa) subjected to in vitro gastric and pancreatic digestion[J]. Food Chemistry, 2007, 102(3): 865-874. DOI:10.1016/ j.foodchem.2006.06.025.
[13] SERRA A, MACIà A, ROMERO M P, et al. Metabolic pathways of the colonic metabolism of fl avonoids (f l avonols, fl avones and fl avanones) and phenolic acids[J]. Food Chemistry, 2012, 130(2): 383-393. DOI:10.1016/j.foodchem.2011.07.055.
[14] SAURA-CALIXTO F, SERRANO J, GO?I I. Intake and bioaccessibility of total polyphenols in a whole diet[J]. Food Chemistry, 2007, 101(2): 492-501. DOI:10.1016/j.foodchem.2006.02.006.
[15] CARDONA F, ANDRéS-LACUEVA C, TULIPANI S, et al. Benef i ts of polyphenols on gut microbiota and implications in human health[J]. Journal of Nutritional Biochemistry, 2013, 24(8): 1415-1422. DOI:10.1016/j.jnutbio.2013.05.001.
[16] QIN B, DAWSON H D, SCHOENE N W, et al. Cinnamon polyphenols regulate multiple metabolic pathways involved in insulin signaling and intestinal lipoprotein metabolism of small intestinal enterocytes[J]. Nutrition, 2012, 28(11/12): 1172-1179. DOI:10.1016/ j.nu t.2012.03.020.
[17] KUBOW S, ISKANDAR M M, SABALLY K, et al. Biotransformation of anthocyanins from two purple-fleshed sweet potato accessions in a dynamic gastrointestinal system[J]. Food Chemistry, 2016, 192: 171-177. DOI:10.1016/j.foodchem.2015.06.105.
[18] PADAYACHEE A, NETZEL G, NETZEL M, et al. Lack of release of bound anthocyanins and phenolic acids from carrot plant cell walls and model composites during simulated gastric and small intestinal digestion[J]. Food and Function, 2013, 4(6): 906-916. DOI:10.1039/ c3fo60091b.
[19] ZHANG Q, RUI X, LI W, et al. Anti-swarming and -biof i lm activities of rose phenolic extract during simulated in vitro gastrointestinal digestion[J]. Food Control, 2016, 64: 189-195. DOI:10.1016/ j.foodcont.2015.12.030.
[20] NEILSON A P, HOPF A S, COOPER B R, et al. Catechin degradation with concurrent formation of homo- and heterocatechin dimers during in vitro digestion[J]. Journal of Agricultural and Food Chemistry, 2007, 55(22): 8941-8949. DOI:10.1021/jf071645m.
[21] TAGLIAZUCCHI D, VERZELLONI E, BERTOLINI D, et al. In vitro bio-accessibility and antioxidant activity of grape polyphenols[J]. Food Chemistry, 2010, 120(2): 599-606. DOI:10.1016/ j.foodchem.2009.10.030.
[22] ACOSTA-ESTRADA B A, GUTIéRREZ-URIBE J A, SERNASALDíVAR S O. Bound phenolics in foods, a review[J]. Food Chemistry, 2014, 152: 46-55. DOI:10.1016/j.foodchem.2013.11.093.
[23] MOSELE J I, MACIà A, ROMERO M P, et al. Stability and metabolism of arbutus unedo bioactive compounds (phenolics and antioxidants) under in vitro digestion and colonic fermentation[J]. Food Chemistry, 2016, 201: 120-130. DOI:10.1016/j.foodchem.2016.01.076.
[24] D’ARCHIVIO M, FILESI C, DI B R, et al. Polyphenols, dietary sources and bioavailability[J]. Annali Dellistituto Superiore Di Sanità, 2007, 43(4): 348-361.
[25] MOSELE J I, MACIà A, ROMERO M P, et al. Application of in vitro gastrointestinal digestion and colonic fermentation models to pomegranate products (juice, pulp and peel extract) to study the stability and catabolism of phenolic compounds[J]. Journal of Functional Foods, 2015, 14: 529-540. DOI:10.1016/j.jff.2015.02.026.
[26] MARTIN K R, APPEL C L. Polyphenols as dietary supplements: a double-edged sword[J]. Nutrition and Dietary Supplements, 2010, 2: 1-12. [27] HE J, GIUSTI M M. Anthocyanins: natural colorants with healthpromoting properties[J]. Annual Review of Food Science and Technology, 2010, 1: 163-187. DOI:10.1146/annurev.food.080708.100754.
[28] REQUENA T, MONAGAS M, POZO-BAYóN M A, et al. Perspectives of the potential implications of wine polyphenols on human oral and gut microbiota[J]. Trends in Food Science and Technology, 2010, 21(7): 332-344. DOI:10.1016/j.tifs.2010.04.004.
[29] MANZANO S, WILLIAMSON G. Polyphenols and phenolic acids from strawberry and apple decrease glucose uptake and transport by human intestinal Caco-2 cells[J]. Molecular Nutrition and Food Research, 2010, 54(12): 1773-1780. DOI:10.1002/mnfr.201000019.
[30] 李素云. 槲皮素及其糖苷在Caco-2細(xì)胞模型上的吸收和代謝研究[D].北京: 中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院, 2010: 45-52.
[31] DANG Y J, ZHU C Y. Genomic study of the absorption mechanism of p-coumaric acid and caffeic acid of extract of Ananas Comosus L. leaves[J]. Journal of Food Science, 2015, 80(3): 504-509. DOI:10.1111/1750-3841.12774.
[32] KOSI?SKA A, ANDLAUER W. Cocoa polyphenols are absorbed in Caco-2 cell model of intestinal epithelium[J]. Food Chemistry, 2012, 135(3): 999-1005. DOI:10.1016/j.foodchem.2012.05.101.
[33] ZUMDICK S, DETERS A, HENSEL A. In vitro intestinal transport of oligomeric procyanidins (DP 2 to 4) across monolayers of Caco-2 cells[J]. Fitoterapia, 2012, 83(7): 1210-1217. DOI:10.1016/j.f i tote.2012.06.013.
[34] RASTOGI H, JANA S. Evaluation of physicochemical properties and intestinal permeability of six dietary polyphenols in human intestinal colon adenocarcinoma Caco-2 cells[J]. European Journal of Drug Metabolism and Pharmacokinetics, 2016, 41(1): 33-43. DOI:10.1007/ s13318-014-0234-5.
[35] KIMURA O, OHTA C, KOGA N, et al. Carrier-mediated uptake of nobiletin, a citrus polymethoxy flavonoid, in human intestinal Caco-2 cells[J]. Food Chemistry, 2014, 154: 145-150. DOI:10.1016/foodchem.2013.12.069.
[36] CHEN M L, YI L, JIN X, et al. Absorption of resveratrol by vascular endothelial cells through passive diffusion and an SGLT1-mediated pathway[J]. Journal of Nutritional Biochemistry, 2013, 24(11): 1823-1829. DOI:10.1016/j.jnutbio.2013.04.003.
[37] KONISHI Y. Transepithelial transport of microbial metabolites of quercetin in intestinal Caco-2 cell monolayers[J]. Journal of Agricultural and Food Chemistry, 2005, 53(3): 601-607. DOI:10.1021/jf0486621.
[38] CHIOU Y S, WU J C, HUANG Q, et al. Metabolic and colonic microbiota transformation may enhance the bioactivities of dietary polyphenols[J]. Journal of Functional Foods, 2014, 7: 3-25. DOI:10.1016/j.jff.2013.08.006.
[39] YANG J, TUCKER G T, ROSTAMI-HODJEGAN A. Cytochrome P450 3A expression and activity in the human small intestine[J]. Clinical Pharmacology and Therapeutics, 2004, 76(4): 391-391. DOI:10.1016/j.clpt.2004.07.001.
[40] KIM S B, CHO S S, CHO H J, et al. Modulation of hepatic cytochrome P450 enzymes by curcumin and its pharmacokinetic consequences in sprague-dawley rats[J]. Pharmacognosy Magazine, 2015, 11(44): 580-584. DOI:10.4103/0973-1296.172965.
[41] KOGA N, OHTA C, KATO Y, et al. In vitro metabolism of nobiletin, a polymethoxy-f l avonoid, by human liver microsomes and cytochrome P450[J]. Xenobiotica, 2011, 41(11): 927-933. DOI:10.3109/00498254. 2011.593208.
[42] BASHEER L, KEREM Z. Interactions between CYP3A4 and dietary polyphenols[J]. Oxidative Medicine and Cellular Longevity, 2015: 1-15. DOI:10.1155/2015/854015.
[43] BOHN T, MCDOUGALL G J, ALEGRíA A, et al. Mind the gapdef i cits in our knowledge of aspects impacting the bioavailability of phytochemicals and their metabolites position paper focusing on carotenoids and polyphenols[J]. Molecular Nutrition and Food Research, 2015, 59(7): 1307-1323. DOI:10.1002/mnfr.201400745.
[44] del RIO D, BORGES G, CROZIER A. Berry fl avonoids and phenolics: bioavailability and evidence of protective effects[J]. British Journal of Nutrition, 2010, 104(3): 67-90. DOI:10.1017/S0007114510003958.
[45] LEE M J, MALIAKAL P L, CHEN L, et al. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability[J]. Cancer Epidemiology Biomarkers and Prevention, 2002, 11: 1025-1032.
[46] JAMES M O, AMBADAPADI S. Interactions of cytosolic sulfotransferases with xenobiotics[J]. Drug Metabolism Reviews, 2013, 45(4): 401-414. DOI:10.3109/03602532.2013.835613.
[47] TANG L, FENG Q, ZHAO J, et al. Involvement of UDP-glucuronosyltranferases and sulfotransferases in the liver and intestinal first-pass metabolism of seven flavones in C57 mice and humans in vitro[J]. Food and Chemical Toxicology, 2012, 50(5): 1460-1467. DOI:10.1016/j.fct.2012.01.018.
[48] CHEN J, LIN H M, HU M. Absorption and metabolism of genistein and its fi ve isof l avone analogs in the human intestinal Caco-2 model[J]. Cancer Chemotherapy and Pharmacology, 2005, 55(2): 159-169. DOI:10.1007/s00280-004-0842-x.
[49] PANDAREESH M D, MYTHRI R B, BHARATH M M S. Bioavailability of dietary polyphenols: factors contributing to their clinical application in CNS diseases[J]. Neurochemistry International, 2015, 89: 198-208. DOI:10.1016/j.neuint.2015.07.003.
[50] KOSTER H, HALSEMA I, SCHOLTENS E, et al. Dose-dependent shifts in the sulfation and glucuronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes: the role of saturation of phenol sulfotransferase[J]. Biochemical Pharmacology, 1981, 30(18): 2569-2575. DOI:10.1016/0006-2952(81)90584-0.
[51] 滕增輝. 天然多酚類化合物的腸道轉(zhuǎn)運(yùn)與代謝研究[D]. 西安: 第四軍醫(yī)大學(xué), 2007: 91-110.
[52] LIU Z H, LIU K X. The transporters of intestinal tract and their study methods[J]. Acta Pharmaceutica Sinica, 2011, 46(4): 370-376.
[53] 張海燕, 平其能. 藥物轉(zhuǎn)運(yùn)蛋白對(duì)燈盞花素小腸吸收的影響[J]. 中國(guó)藥科大學(xué)學(xué)報(bào), 2007, 38(1): 60-64. DOI:10.3321/ j.issn:1000-5048.2007.01.015.
[54] 何卉, 陳西敬, 王廣基. 白藜蘆醇及其糖苷白藜蘆醇苷與藥物外排轉(zhuǎn)運(yùn)體的相互作用研究[J]. 中國(guó)臨床藥理學(xué)與治療學(xué), 2008, 13(4): 366-372.
[55] 王婷婷, 李偉, 袁勇, 等. 大鼠單向灌流模型研究田薊苷的在體腸吸收[J]. 中國(guó)中藥雜志, 2013, 38(7): 1079-1082. DOI:10.4268/ cjcmm20130731.
[56] HOLLMAN P C H, CASSIDY A, COMTE B, et al. The biological relevance of direct antioxidant effects of polyphenols for cardiovascular health in humans is not established[J]. The Journal of Nutrition, 2011, 141(5): 989-1009. DOI:10.3945/jn.110.131490.
Progress in Research on Dietary Polyphenols Metabolism Based on a Mechanism Involving Intestinal Absorption
ZUO Dan1, LIAO Xia1, LI Yao1, SHI Fang1, WANG Liying1, MING Jian1,2,*
(1. College of Food Science, Southwest University, Chongqing 400715, China; 2. Chongqing Engineering Research Center of Regional Food, Chongqing 400715, China)
Dietary polyphenols, an important class of components in plant-derived foods, is not only directly related to the fl avor and color of foods, but also is helpful for maintaining human health. Since they are easily changed during release from the matrix, digestion, absorption, metabolism and distribution to various tissues in the body, the bioavailability of different dietary polyphenols is different. The most abundant dietary polyphenols do not necessarily represent the highest bioavailability. The absorption and biotransformation of plant polyphenols as well as their bioavailability are one of the current hot research topics. In this article, the gastrointestinal digestion, absorption and metabolism of dietary polyphenols are reviewed based on a mechanism involving intestinal absorption, with the aim to provide valuable information for the research and development of polyphenolics-rich health foods.
dietary polyphenols; bioavailability; absorption; metabolism; transportation
10.7506/spkx1002-6630-201707042
Q964.8;R151.2
A
1002-6630(2017)07-0266-06
左丹, 廖霞, 李瑤, 等. 基于腸道吸收機(jī)制的膳食多酚代謝研究進(jìn)展[J]. 食品科學(xué), 2017, 38(7): 266-271. DOI:10.7506/ spkx1002-6630-201707042. http://www.spkx.net.cn
ZUO Dan, LIAO Xia, LI Yao, et al. Progress in research on dietary polyphenols metabolism based on a mechanism involving intestinal absorption[J]. Food Science, 2017, 38(7): 266-271. (in Chinese with English abstract)
10.7506/ spkx1002-6630-201707042. http://www.spkx.net.cn
2016-05-17
國(guó)家自然科學(xué)基金面上項(xiàng)目(31471576);中央高?;究蒲袠I(yè)務(wù)費(fèi)專項(xiàng)(XDJK2015D035)
左丹(1992—),女,碩士研究生,研究方向?yàn)槭称坊瘜W(xué)與營(yíng)養(yǎng)學(xué)。E-mail:804403185@qq.com
*通信作者:明建(1972—),男,教授,博士,研究方向?yàn)槭称坊瘜W(xué)與營(yíng)養(yǎng)學(xué)。E-mail:mingjian1972@163.com