彭麗倩 陳教全 尹忠浩 梁碧華
[摘要]天然抗氧化劑來(lái)源廣泛、品種繁多,主要包括多酚類(lèi)、多糖類(lèi)、黃酮類(lèi)、皂甙類(lèi)、鞣質(zhì)類(lèi)及褪黑素類(lèi)等,其能夠清除活性氧、拮抗氧化應(yīng)激損傷,調(diào)控細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)通路,為UV損傷相關(guān)性皮膚病、色素性皮膚病、真菌感染性皮膚病、紅斑丘疹鱗屑性皮膚病及過(guò)敏性紫癜等治療提供了廣闊的前景。本文著重就天然抗氧化劑的分類(lèi)、作用機(jī)理及其在氧化損傷相關(guān)性皮膚病的防治作用方面進(jìn)行綜述。
[關(guān)鍵詞]天然抗氧化劑;皮膚病;氧化應(yīng)激;多酚類(lèi);多糖類(lèi);黃酮類(lèi)
Abstract: Natural antioxidants are abundant and widespread, mainly including polyphenols, polysaccharides, flavonoids, saponins, tannins, melatonin. Also it has properties of scavenging radicals, antagonizing oxidative damage and adjusting cell signaling transduction. Up to this point, it provides a broad prospect for the treatment of dermatosis, for instance dermatosis induced by ultraviolet, pigmented dermatosis, mycosis, dermatosis characterized by erythematous and scaling papules, allergic purpura. The paper focus on the classification and action mechanism of natural antioxidants and combatting of oxidative stress dermatosis.
Key words:natural antioxidant; dermatosis; oxidative stress;polyphenols;? polysaccharides; flavonoids
皮膚作為人體最大的器官,是抵御外界機(jī)械、化學(xué)、物理及生物等各種刺激的第一道防線。而UV照射或臭氧、苯并芘等污染物誘導(dǎo)細(xì)胞產(chǎn)生大量的活性氧(Reactive oxygen species, ROS),生成脂質(zhì)過(guò)氧化物,誘發(fā)氧化應(yīng)激損傷及炎癥反應(yīng),打破體內(nèi)氧化/抗氧化系統(tǒng)平衡,使機(jī)體組織衰退、生理功能低下,損傷皮膚屏障,導(dǎo)致皮膚老化。而隨著國(guó)民生活素質(zhì)水平的提高及醫(yī)學(xué)發(fā)展的進(jìn)步,人類(lèi)壽命的延長(zhǎng),人們對(duì)皮膚的保養(yǎng)越來(lái)越重視,而天然抗氧化劑來(lái)源廣泛,具有安全有效、天然無(wú)毒、防御氧化損傷及延緩衰老等特性,成為皮膚科領(lǐng)域的研究熱點(diǎn)。天然抗氧化劑品種繁多,故本文重點(diǎn)就天然抗氧化劑的分類(lèi)、作用機(jī)制及其與氧化損傷相關(guān)性皮膚病進(jìn)行綜述。
1? 天然抗氧化劑的分類(lèi)
無(wú)論是通俗文學(xué)還是科學(xué)文獻(xiàn),對(duì)“抗氧化劑”尚無(wú)一個(gè)明確的定義[1]。一般來(lái)講,抗氧化劑指能清除外來(lái)的或內(nèi)源性生成的ROS,抑制脂質(zhì)過(guò)氧化反應(yīng),拮抗DNA損傷[2],保護(hù)生物體完整性。
依據(jù)其結(jié)構(gòu)可分為非酶類(lèi)和酶類(lèi)抗氧化劑。酶類(lèi)抗氧化劑:超氧化物歧化酶(Superoxide Dismutase,SOD)、谷胱甘肽過(guò)氧化物酶(Glutathione peroxidase, GSH-Px)、過(guò)氧化氫酶(Catalase,CAT)、醛酮還原酶(Aldo-keto reductase, AKRs)等;非酶類(lèi)抗氧化劑:天然的植物抗氧化劑、維生素類(lèi)、胡蘿卜素類(lèi)等重點(diǎn)介紹的天然植物抗氧化劑主要包括多酚類(lèi)、多糖類(lèi)、黃酮類(lèi)、皂甙類(lèi)、鞣質(zhì)類(lèi)、褪黑素類(lèi)等。
1.1 多酚類(lèi):多酚類(lèi)抗氧化劑包含表沒(méi)食子兒茶素沒(méi)食子酸酯(EGCG)、表沒(méi)食子兒茶素(EGC)、表兒茶素沒(méi)食子酸酯(ECG)等,EGCG是綠茶含量最豐富的活性物質(zhì);研究證實(shí),綠茶具有抗氧化、抗炎、抗衰老、抗應(yīng)激、保護(hù)神經(jīng)及誘導(dǎo)自噬等功能[3],抑制心血管疾病、癌癥、阿爾茨海默病、帕金森病,以及糖尿病等慢性病的發(fā)生[4]。最新研究發(fā)現(xiàn),綠茶可能是治療炎癥性腸病的一種新手段,通過(guò)調(diào)節(jié)Nrf2、絲裂原活化蛋白激酶等途徑,提高抗氧化酶的活性,降低TNF-α、IL-1β、IL-6、IL-8、IL-17等的活性;抑制環(huán)氧化酶介導(dǎo)的IkB激酶和NFkB的轉(zhuǎn)錄,阻遏氧化應(yīng)激的反應(yīng)[4]。Li Y等[5]學(xué)者發(fā)現(xiàn),茶多酚可通過(guò)較強(qiáng)的抗氧化作用,調(diào)理腸道微生物群,對(duì)于宿主的健康產(chǎn)生正面的影響。
從姜科類(lèi)植物姜黃根中提取的一種黃色的成分—姜黃素,為酸性多酚類(lèi)。是AP-1、核因子-kB的抑制物,還可抑制c-Jun N端激酶的活性,有效拮抗UV輻射誘導(dǎo)的DNA損傷,具有抗氧化、抗炎及抗增殖等作用。Liu X等[6]發(fā)現(xiàn)姜黃素能夠減輕UV誘導(dǎo)的人皮膚成纖維細(xì)胞的DNA損傷,清除細(xì)胞內(nèi)ROS,致過(guò)氧化脂質(zhì)水平下降,防護(hù)光損傷。最新研究已證實(shí),姜黃素能夠激活MAPK-Nrf2/ARE通路,上調(diào)CAT、SOD、GSH-Px等抗氧化酶基因的表達(dá),減少ROS、MDA含量,遏止氧化應(yīng)激損傷,發(fā)揮抗氧化效用[6]。
紫檀芪是白藜蘆醇的第3位和第5位兩個(gè)酚羥基被甲氧基替代所衍生的非黃酮類(lèi)多酚化合物,能夠激活Bcl-2相關(guān)X蛋白的表達(dá),減少ROS生成具有抗炎、抗氧化、抗老化、鎮(zhèn)痛等作用[7-8]。Li H等[9]報(bào)道,紫檀芪可調(diào)控PI3K介導(dǎo)的Nrf2/ARE信號(hào)途徑,提高抗氧化酶的活性,清除UV致ROS,減弱DNA損傷,拮抗UVB導(dǎo)致角質(zhì)形成細(xì)胞損傷。
1.2 多糖類(lèi):枸杞多糖是從枸杞果實(shí)中提取出來(lái)的水溶性的天然植物多糖,具有抗氧化、抗衰老、抗輻射、抗腫瘤等多種功效,枸杞多糖可激活Nrf2通路,提高SOD、GSH-Px等抗氧化酶活性,降低ROS水平,減輕氧化應(yīng)激損害。除此,其通過(guò)介導(dǎo)p53信號(hào)通路,降低p53、p21、bax基因的表達(dá),增加雙微體基因2和端粒酶基因表達(dá),抑制機(jī)體氧化應(yīng)激反應(yīng)及細(xì)胞凋亡過(guò)程[10-11]。
[2]Clark SF.The biochemistry of antioxidants revisited[J].Nutr Clin Pract,2002,17(1):5-17.
[3]Prasanth MI,Sivamaruthi BS,Chaiyasut C,et al.A review of the role of green tea (camellia sinensis) in antiphotoaging, stress resistance, neuroprotection,and autophagy[J].Nutrients,2019,11(2):474.
[4]Xing L,Zhang H,Qi R,et al.Recent advances in the understanding of the health benefits and molecular mechanisms associated with green tea polyphenols[J].J Agric Food Chem,2019,67(4):1029-1043.
[5]Barbalho SM,Bosso H,Salzedas-Pescinini LM,et al.Green tea: A possibility in the therapeutic approach of inflammatory bowel diseases?Green tea and inflammatory bowel diseases[J].Complement Ther Med,2019,43:148-153.
[6]Wu J,Ibtisham F,Niu YF,et al.Curcumin inhibits heat-induced oxidative stress by activating the MAPK-Nrf2 / ARE signaling pathway in chicken fibroblasts cells[J].J Therm Biol,2019,79:112-119.
[7]Liu X,Zhang R,Shi H,et al.Protective effect of curcumin against ultraviolet A irradiationinduced photoaging in human dermal fibroblasts[J].Mol Med Rep,2018,17(5):7227-7237.
[8]Li YR,Li S,Lin CC.Effect of resveratrol and pterostilbene on aging and longevity[J].Biofactors,2018,44(1):69-82.
[9]Li H,Jiang N,Liang B,et al.Pterostilbene protects against UVB-induced photo-damage through a phosphatidylinositol-3-kinase-dependent Nrf2/ARE pathway in human keratinocytes[J].Redox Rep,2017,22(6):501-507.
[10]Liang B,Peng L,Li R,et al.Lycium barbarum polysaccharide protects HSF cells against ultraviolet-induced damage through the activation of Nrf2[J].Cell Mol Biol Lett,2018,23:18.
[11]Xia G,Xin N,Liu W,et al.Inhibitory effect of Lycium barbarum polysaccharides on cell apoptosis and senescence is potentially mediated by the p53 signaling pathway[J].Mol Med Rep, 2014,9(4):1237-1241.
[12]Yan M,Liu Z,Yang H,et al.Luteolin decreases the UVAinduced autophagy of human skin fibroblasts by scavenging ROS[J].Mol Med Rep, 2016,14(3):1986-1992.
[13]Lee SW,Kim JH,Song H,et al.Luteolin 7-sulfate attenuates melanin synthesis through inhibition of creb- and mitf-mediated tyrosinase expression[J].Antioxidants (Basel),2019,8(4):87.
[14]Zhuang W,Yue L,Dang X,et al.Rosenroot (rhodiola): potential applications in aging-related diseases[J].Aging Dis, 2019,10(1):134-146.
[15]Lin KT,Chang TC,Lai FY,et al.Rhodiola crenulata attenuates gamma-ray induced cellular injury via modulation of oxidative stress in human skin cells[J].Am J Chin Med,2018,46(1):175-190.
[16]Bonomini F,Borsani E,F(xiàn)avero G,et al.Dietary melatonin supplementation could be a promising preventing/therapeutic approach for a variety of liver diseases[J].Nutrients,2018,10(9):1135.
[17]Karaaslan C,Suzen S.Antioxidant properties of melatonin and its potential action in diseases[J].Curr Top Med Chem, 2015,15(9):894-903.
[18]劉清,江娜,朱慧蘭.植物來(lái)源的抗氧化劑及其在皮膚科的應(yīng)用[J].皮膚性病診療學(xué)雜志,2015,22(4):339-342.
[19]彭麗倩,江娜,劉清,等.枸杞多糖抗氧化機(jī)制及其在皮膚科的研究進(jìn)展[J].國(guó)際皮膚性病學(xué)雜志,2017,43(1):39-42.
[20]Sharma M,Manoharlal R,Puri N,et al.Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1? in Candida albicans[J].Biosci Rep,2010,30(6):391-404.
[21]Fei WJ,Yuan LP,Lu L,et al.Protective effect of total flavones of bidens pilosa L. On iga1 induced injury of huvecs in henoch-schonlein purpura children patients[J].Zhongguo Zhong Xi Yi Jie He Za Zhi, 2016,36(2):183-187.
[22]Saric S,Notay M,Sivamani RK.Green tea and other tea polyphenols: effects on sebum production and acne vulgaris[J].Antioxidants (Basel), 2016,6(1):2.