山藥活性成分及營(yíng)養(yǎng)功能研究進(jìn)展
摘要 山藥是中國(guó)傳統(tǒng)的藥食同源植物,有悠久的栽培和食用歷史。山藥營(yíng)養(yǎng)豐富,含多糖、多酚、皂苷等活性成分,具有多種生理功能。本文綜述山藥中主要活性成分及其調(diào)節(jié)免疫、抗炎、益腸胃、調(diào)節(jié)糖脂代謝、抗氧化等功能的作用機(jī)制,并展望其應(yīng)用前景,為山藥相關(guān)研究提供理論依據(jù)。
山藥(Chinese yam,CY)又稱薯蕷、土薯、薯藥等,為薯蕷科 (Dioscoreaceae) 薯蕷屬(Dioscorea L.)植物薯蕷(Dioscoreaopposita Thunb.)[1]。我國(guó)是山藥的原產(chǎn)地,自夏、商開始種植[2],目前形成東北、華北、西北、華中華東、華南5 個(gè)產(chǎn)區(qū),其中河南省種植面積達(dá)到7 萬hm2[3]。山藥味甘性平,歸脾、肺、腎經(jīng)[4],主要功能成分包括多糖、多酚類化合物、皂苷、尿囊素等[5-6]。本文根據(jù)近5年研究,綜述山藥組成成分的理化性質(zhì),功能活性及作用機(jī)制,并預(yù)測(cè)其應(yīng)用前景,為其作為藥食同源性食品的研究提供理論依據(jù)。
1 山藥主要活性成分研究
山藥營(yíng)養(yǎng)物質(zhì)豐富,以古懷慶者(今河南焦作)最佳。如表1所示,以鐵棍山藥和普通山藥為例,顯示其營(yíng)養(yǎng)成分的占比[7]。山藥中活性物質(zhì)有多糖、多酚、磷脂、山藥素(I、II、III、Ⅳ、V)、鹽酸山藥堿、槭素Ⅱ、多酚氧化酶等,包括皂苷、尿囊素、多巴胺、膽甾醇、β 谷甾醇、麥角甾醇、菜油甾醇等多種有機(jī)化合物,另外含有維生素C、微量元素I、Ca、Fe、P[3,8-9]。
表1 山藥的主要營(yíng)養(yǎng)組成(%)
Table 1 Main nutrient composition of Chinese yam(%)
?
近年來,國(guó)內(nèi)外的研究主要集中在多糖、多酚、薯蕷皂苷、尿囊素等物質(zhì)上,這些化學(xué)成分決定山藥的營(yíng)養(yǎng)價(jià)值和作用活性。山藥多糖(Chinese yam polysaccharide,CYP)的干粉含量約為7.4%~13.5%[10],主要由甘露糖、阿拉伯糖、木糖、葡萄糖、半乳糖及少量巖藻糖組成[11]。其組分隨提取條件的不同存在差異,低溫浸提得到的多糖主要由甘露糖組成,高溫煎煮得到的多糖主要由葡萄糖組成[12]。山藥多糖具有增強(qiáng)體液免疫、抗氧化、抗腫瘤、調(diào)節(jié)胃腸道、降血糖等多種功能。
多酚是山藥中重要的抗氧化物質(zhì),含量約為0.08%~0.11%[13-14]。研究發(fā)現(xiàn),總酚含量由多至少依次為白肉山藥>紅肉山藥>黃肉山藥,而且肉色越深山藥的總酚化合物含量越高。由于總酚由類黃酮、酚酸和單寧這3 種酚類化合物構(gòu)成,研究山藥生長(zhǎng)中多酚含量變化,發(fā)現(xiàn)類黃酮是最主要的酚類物質(zhì),占到六成以上,主要由花青素和黃酮醇構(gòu)成[15]。紫山藥(Dioscoreaalata)的肉質(zhì)部和表皮均含有較多類黃酮化合物等酚類抗氧化物質(zhì),并且山藥皮中含量較高[16]。
薯蕷皂苷(Diosgenin,DG)由螺甾烷型的薯蕷皂苷元和糖鏈以糖苷鍵相連,分子結(jié)構(gòu)如圖1所示,在山藥干粉中占0.6%~1.0%[17],在皮中含量最高[18]。近年來,關(guān)于薯蕷皂苷的功能性研究主要集中在調(diào)節(jié)免疫、抗腫瘤、抗炎鎮(zhèn)痛、保護(hù)胃腸黏膜等方面。此外,在山藥小分子活性成分的研究領(lǐng)域,以尿囊素(Allantoin)、膽堿(Choline)的研究居多[5]。尿囊素是咪唑類化合物,分子式為C4H6N4O3,分子結(jié)構(gòu)如圖1所示。尿囊素是山藥主要的有效成分之一,占比在0.9%~1.0%之間,其含量在山藥及其產(chǎn)品的質(zhì)量評(píng)價(jià)上起著重要指標(biāo)作用[17]。
圖1 山藥活性物質(zhì)(薯蕷皂苷和尿囊素)的分子結(jié)構(gòu)
Fig.1 Molecular structures of Chinese yam active constituents (diosgenin and allantoin)
2 山藥的營(yíng)養(yǎng)功能研究
山藥氣味平和,溫補(bǔ)而不驟,微香而不燥,是中醫(yī)常用的一味健脾補(bǔ)氣良藥[19]。關(guān)于山藥營(yíng)養(yǎng)功效始載于《神農(nóng)本草經(jīng)》,稱“能補(bǔ)虛贏,益氣力,久服耳目聰明,輕身延年”?!侗静菥V目》將其概括為“益腎氣,健脾胃,止泄痢,化痰涎,潤(rùn)皮”五大功用[5]。
2.1 調(diào)節(jié)免疫
如表2所示,CYP 可提高T 淋巴細(xì)胞增殖能力和 NK 細(xì)胞活性,同時(shí)促進(jìn)白細(xì)胞介素2(Interleukin-2,IL-2)、腫瘤壞死因子(Tumor necrosis factor α,TNF-α)、干擾素-γ(Interferonγ,IFN-γ)、主要組織相容性復(fù)合體(Major histocompatibility complex,MHC)水平升高[20-23]。除了增強(qiáng)體液免疫,CYP 還能促進(jìn)吞噬細(xì)胞向M1型極化,激活其吞噬能力,增強(qiáng)細(xì)胞免疫功能[24],其中作用機(jī)制包括調(diào)節(jié)Toll 樣受體4 (Toll like receptor 4,TLR4)-核因子κB(Nuclear factor κB,NFκB),促進(jìn)細(xì)胞外信號(hào)調(diào)節(jié)蛋白激酶(Extracellular -signal regulated protein kinase,ERK)、c-Jun N 末端蛋白激酶(c-Jun N-terminal kinase,JNK)、p38 絲裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38) 磷酸化,激活絲裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)途徑[25]。除此之外,可以緩解卡介苗和脂多糖 (Lipopolysaccharide,LPS) 誘導(dǎo)的肝指數(shù)、脾指數(shù)降低[26]。
表2 山藥免疫功能研究現(xiàn)狀
Table 2 Research status of immune function of Chinese yam
注:YMP.山藥黏多糖;CY-W.山藥水提取物;NS-CYP.非淀粉多糖。
受試物 實(shí)驗(yàn)?zāi)P?作用效果及機(jī)制 參考文獻(xiàn)山藥多糖 荷瘤C57BL/6 小鼠(i.g.150 mg/kg CYP)、SD 大鼠 (0.25/0.5 g/kg CYP diet)、結(jié)腸癌BALB/c 裸鼠(i.g.125 mg/kg CY-W)、肝損傷KM 小鼠(i.g.120 mg/kg CYP)、腹腔巨噬細(xì)胞(50,100 μg/mL YMP)、RAW264.7細(xì)胞(400,800 μg/mL NS-CYP)增強(qiáng)體液免疫:包括提高T 細(xì)胞增殖能力(IL-2↑、IFN-γ↑、MHC↑),增強(qiáng)NK 細(xì)胞活性;增強(qiáng)細(xì)胞免疫:促進(jìn)巨噬細(xì)胞向M1 極化,提高巨噬細(xì)胞吞噬能力;調(diào)節(jié)TLR4-NFκB信號(hào)通路,激活巨噬細(xì)胞吞噬能力;通過P13 激酶介導(dǎo)的ERK1/2、JNK1/2、P38 磷酸化,激活MAPK 途徑,抑制腫瘤壞死因子表達(dá)(TNF↓);消除自由基(GSH↑、GSH-Px↑),保護(hù)免疫性肝損傷;抗脂質(zhì)過氧化(ALT↓、AST↓、MDA↓),保護(hù)線粒體膜,促進(jìn)肝細(xì)胞生長(zhǎng)[20]~[26],[28],[29]薯蕷皂苷 結(jié)腸炎C57BL/6 小鼠 (i.p.25 mg/kg 薯蕷皂苷)、小兒UC 患者結(jié)腸LPMCs(200 ng/mL 薯蕷皂苷)山藥皮 淡水養(yǎng)殖鯉魚模型 (質(zhì)量分?jǐn)?shù)2%的山藥皮)低劑量增強(qiáng)IEC 先天免疫力 (AMP↑、β-defensin1↑、βdefensin10↑、RegIIIγ↑);高劑量控制過度的適應(yīng)性免疫反應(yīng),減少促炎因子產(chǎn)生(TNF-α↓、IL-1β↓、IFN-γ↓)和NFκB,減少炎性細(xì)胞存活(LPMC↓)調(diào)節(jié)腸道菌群(擬桿菌↑、黃桿菌↑、乳桿菌↑、腸桿菌↓、希瓦氏菌↓、假單胞菌↓、SCFAs↑);修復(fù)腸道防御屏障(CAT↑、SOD↑、IL-1β↓、occludin↑和ZO-1↑、通路因子TLR4-NFκB↑)[27][6]
低劑量薯蕷皂苷治療可以促進(jìn)抗菌肽(Antimicrobial peptide,AMP)表達(dá),上調(diào)AMP 相關(guān)基因如β-防御素(β-defensin)、RegIIIγ,增強(qiáng)腸上皮細(xì)胞(Intestinal epithelial cell,IEC)增殖,從而激活免疫;而高劑量薯蕷皂苷可以減少促炎因子和固有層單核細(xì)胞(lamina propria mononuclear cells,LPMC)水平,控制過度的適應(yīng)性免疫反應(yīng)。總之,薯蕷皂苷可以通過修復(fù)腸黏膜屏障,發(fā)揮腸道免疫功能[27]。
此外,研究顯示飼喂山藥皮能夠提升腸道酶活性和抗炎水平,增加短鏈脂肪酸 (Short-chain fatty acids,SCFAs)含量,抑制腸道病原體生長(zhǎng)。作為水產(chǎn)養(yǎng)殖飼料添加劑,提升鯉魚免疫力[6]。
2.2 抗炎
體內(nèi)炎癥反應(yīng)與阿爾茲海默癥(Alzheimer's disease,AD)、炎癥性腸?。↖nflammatory bowel disease,IBD)、動(dòng)脈粥樣硬化、肥胖等慢性疾病的發(fā)生息息相關(guān)[29]。如表3所示,山藥全粉明顯上調(diào)碳酸酐酶活性,下調(diào)iNOS、COX-2、IL-1β、IL-6、TNF-α 等炎癥因子水平,對(duì)炎癥有干預(yù)效果[30]。山藥皮提取物可以顯著降低一氧化氮(Nitric oxide,NO)、粒細(xì)胞-巨噬細(xì)胞集落刺激因子(Granulocyte -macrophage colony -stimulating factor,GM-CSF)的表達(dá),促進(jìn)p65 核位移,并且抑制ROS 產(chǎn)生,通過轉(zhuǎn)錄因子NF-E2 相關(guān)因子2(Nuclear factor (erythroid-derived 2)-like 2,Nrf2)核位移,上調(diào)下游抗氧化酶,如血紅素加氧酶(Heme oxygenase,HO)-1、腺嘌呤二核苷酸醌氧化還原酶(NADPH quinine oxidoreductase,NQO)-1[31]。
表3 山藥抗炎功能研究現(xiàn)狀
Table 3 Research status of anti-inflammatory function of Chinese yam
受試物 實(shí)驗(yàn)?zāi)P?作用效果及機(jī)制 參考文獻(xiàn)山藥全粉 半胱胺誘導(dǎo)的十二指腸潰瘍SD 大鼠(i.g.400 mg/kg,2 g/kg CY)COX-2↓、iNOS↓、IL-1β↓、IL-6↓、TNF-α↓,CA IX、XII 和XIV↑[30]山藥皮 LPS 誘 導(dǎo)RAW264.7 細(xì) 胞,H2O2 誘 導(dǎo)HCT116 結(jié)腸上皮細(xì)胞 (50,100 μg/mL CY peel),DSS 誘 導(dǎo) 結(jié) 腸 炎BALB/c 小鼠(i.g.50,100 mg/kg CY peel)薯蕷皂苷 3T3-11 脂肪細(xì)胞和巨噬細(xì)胞共培養(yǎng)(10 μmol/L 薯蕷皂苷),LPS 誘導(dǎo)的PD大鼠 (i.p.10 mmol/kg·L 薯蕷皂苷),卵清蛋白致敏BALB/c 小鼠 (i.g.100,200 mg/kg 薯蕷皂苷),棕櫚酸酯誘導(dǎo)人臍靜脈內(nèi)皮細(xì)胞(0.25,0.5 μg/mL 薯蕷皂苷)降低炎性細(xì)胞因子的表達(dá)(NO↓、GM-CSF↓、IL-1β↓、IL-6↓、IL-12↑、TNF-α↓、iNOS↓、COX-2↓、p65 核位移↓);抑制氧化應(yīng)激(ROS↓),通過Nrf2 核位移上調(diào)下游抗氧化酶(HO-1↑、NQO-1↑)緩解機(jī)體炎癥(CK-2↓、JNK↑、NF-κB↑、AP-1↑),減少巨噬細(xì)胞產(chǎn)生炎性介質(zhì)(ROS↓、IL-1↓、IL-6↓);促進(jìn)脂肪細(xì)胞分化,抑制炎癥;抑制TLR- NFκB 信號(hào)通路;增強(qiáng)腸道T 細(xì)胞免疫,消除體內(nèi)過敏原;阻斷IKKβ/IRS-1 通路,調(diào)節(jié)MAPK/Akt/NFκB 信號(hào)通路,緩解動(dòng)脈粥樣硬化病變相關(guān)炎癥(改善內(nèi)皮紊亂及胰島素抵抗)[31][30],[35]~[38]
進(jìn)一步發(fā)現(xiàn),山藥中主要抗炎成分為多酚類物質(zhì)和皂苷類物質(zhì),山藥皮中的多酚成分包含沒食子酸、阿魏酸等[32]。體外實(shí)驗(yàn)結(jié)果證明,山藥多
酚能夠促進(jìn)神經(jīng)生長(zhǎng)因子 (Nerve growth factor,NGF)表達(dá),抑制NO 水平,主要作用機(jī)制為抑制JNK 信號(hào)通路[14,33]。紫山藥(Dioscorea alata)中的花青素可以降低小鼠體內(nèi)促炎因子水平,改善氧化應(yīng)激,提升一系列緊密連接蛋白(Tight junction protein 1,ZO-1)水平,維護(hù)屏障完整[16]。薯蕷皂苷的抗炎機(jī)制是通過抑制蛋白激酶(Casein kinase,CK)-2,激活JNK、NF-κB,激活子蛋白(Activator protein,AP)-1,抑制巨噬細(xì)胞分泌炎性因子,并且可以促進(jìn)脂肪細(xì)胞分化,抑制肥胖誘導(dǎo)的炎癥[34];抑制Toll 樣受體 (Toll-like receptors,TLR)TLRNFκB 信號(hào)通路,緩解帕金森癥(Parkinson's Disease,PD)誘導(dǎo)產(chǎn)生的運(yùn)動(dòng)障礙及炎癥[35];在過敏小鼠體內(nèi)增強(qiáng)腸道T 細(xì)胞免疫,消除體內(nèi)過敏原,發(fā)揮抗炎作用[36];阻斷IKKβ/IRS-1 通路,改善內(nèi)皮紊亂及胰島素抵抗,通過MAPK/Akt/NFκB 信號(hào)通路緩解動(dòng)脈粥樣硬化病變相關(guān)炎癥[37]。
2.3 改善胃腸屏障
山藥具有健脾補(bǔ)虛,治療腸胃失調(diào),促進(jìn)消化的功效。如表4所示,山藥組分能夠有效緩解抗生素誘導(dǎo)的體重降低,增強(qiáng)胃腸蠕動(dòng),使宿主代謝表型趨于正常,從而改善腸道失調(diào)[4]。另外,還可以預(yù)防急性胃潰瘍,其機(jī)制與氧化應(yīng)激作用有關(guān)[38]。
表4 山藥改善胃腸屏障功能研究現(xiàn)狀
Table 4 Research status of beneficial gastrointestinal barrier function of Chinese yam
受試物 實(shí)驗(yàn)?zāi)P?作用效果及機(jī)制 參考文獻(xiàn)山藥全粉 抗生素誘導(dǎo)Wistar 大鼠 (i.g.3.4 g/kg CYW),消炎痛誘導(dǎo)胃潰瘍KM 小鼠(i.g.2.5,7.5 g/kg CY)增強(qiáng)胃腸蠕動(dòng)(SIP↑),腎保護(hù)(尿量↓,尿酸再吸收↓);改善腸道失調(diào),保護(hù)胃黏膜[4],[38]山藥多糖 鹽酸林可霉素誘導(dǎo)腸道菌群失調(diào)Wistar 大鼠(p.o.合生元膠囊,含CYP 0.04 g,0.02 g,0.01 g/粒),大黃水煎液誘導(dǎo)脾虛KM 小鼠(i.g.10 g/kg CYP)尿囊素 臨床治療胃炎及消化性潰瘍患者(p.o.尿囊素鋁0.2 g,3 次/d),耐藥性近平滑念珠菌(Candida parapsilosis)(尿囊素納米顆粒),消炎痛誘導(dǎo)胃潰瘍Albino Swiss 小鼠(p.o.尿囊素60 mg/kg)調(diào)節(jié)肝功能相關(guān)酶的活性 (總膽紅素↑、ALT↑),調(diào)節(jié)胃腸激素水平(血管活性腸肽↑、胃動(dòng)素↑、生長(zhǎng)抑素↑和P 物質(zhì)↑),改善胃腸道對(duì)水和電解質(zhì)的運(yùn)輸能力(GE↑、SIP↑);優(yōu)化腸道菌群結(jié)構(gòu)(梭菌綱↑、芽孢桿菌綱↑、產(chǎn)芽孢桿菌綱↑),調(diào)節(jié)腸道微生態(tài)(雙歧桿菌↑、乳酸桿菌↑、大腸桿菌↓、糞腸球菌↓、SCFAs↑);在腸道上皮細(xì)胞表面形成親水凝膠層,維護(hù)腸道屏障結(jié)構(gòu)促進(jìn)黏液合成及分泌,減輕有害物對(duì)胃黏膜細(xì)胞的損傷,保護(hù)胃腸黏膜[40]~[45][43],[45],[46]
CYP 能顯著抑制脾虛小鼠胃排空(Gastric emptying,GE)及小腸推進(jìn)(Small intestinal propulsion,SIP),促進(jìn)小腸吸收[39]。胃腸激素又稱腦腸肽,其水平與腸道蠕動(dòng)及傳輸密切相關(guān)。將CYP 與雙歧桿菌結(jié)合制備微生態(tài)調(diào)節(jié)劑,可以改善胃腸道對(duì)水和電解質(zhì)的運(yùn)輸能力,調(diào)節(jié)腦腸肽水平[40]。CYP 還能夠上調(diào)有益菌,下調(diào)有害菌,改善菌群多樣性,增加SCFA 生成[41]。CYP 可以調(diào)節(jié)脾虛小鼠體內(nèi)環(huán)氧化酶2 (Cyclooxygenase-2,COX-2)、誘導(dǎo)性一氧化氮合酶 (Induced nitric oxide synthase,iNOS)、IL-1β、IL-6、TNF-α 的 表達(dá)。綜上所述,CYP 主要通過增強(qiáng)機(jī)體免疫,調(diào)節(jié)炎癥因子水平及相關(guān)激素酶活,維護(hù)腸道屏障完整性,達(dá)到治療胃潰瘍,調(diào)節(jié)腸道菌群的作用[42]。
臨床采用尿囊素鋁治療胃炎及消化性潰瘍患者,研究表明,尿囊素具有抗刺激物,消炎抑菌,生肌作用,可用于胃及十二指腸潰瘍,能夠減輕有害物對(duì)胃黏膜細(xì)胞的損傷,保護(hù)胃腸黏膜[43]。
2.4 調(diào)節(jié)糖脂代謝
山藥具有調(diào)節(jié)糖脂代謝的功效。山藥中抗性淀粉可以減緩餐后血糖效應(yīng),其中,黏液蛋白也發(fā)揮了降血糖的功效[5]。如表5所示,CYP 能提高己糖激酶(Hexokinase,HK)、琥珀酸脫氫酶(Succinate dehydrogenase,SDH)活性,降低血清總膽固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)、低密度脂蛋白膽固醇(Low density lipoprotein cholesterol,LDL-C)、丙二醛(Malondialdehyde,MDA)含量,增加高密度脂蛋白膽固醇(High density lipoprotein cholesterol,HDL-C)含量[32,47-48]。除此之外,CYP 顯著增加胰島細(xì)胞存活率,促進(jìn)抗凋亡基因bcl-2 的表達(dá),上調(diào)胰島素受體 (INSR)、胰島素受體底物(Insulin receptor substrate,IRS)、磷脂酰肌醇3 激酶(Phosphatidylinositol 3kinase,PI3K)水平,改善胰島素分泌[10,49]。并且協(xié)同抗氧化作用,激活超氧化物岐化酶(Superoxide dismutase,SOD)、過氧化氫酶(Catalase,CAT)、GSH-Px,發(fā)揮降血糖、血脂的功能[42,50]。
表5 山藥調(diào)節(jié)糖脂代謝功能研究現(xiàn)狀
Table 5 Research status of regulating glucose and lipid metabolism function of Chinese yam
受試物 實(shí)驗(yàn)?zāi)P?作用效果及機(jī)制 參考文獻(xiàn)山藥多糖 四氧嘧啶誘導(dǎo)Ι 型糖尿病SD 大鼠(i.g.240,400 mg/kg CYP),高脂飲食及鏈脲佐菌素誘導(dǎo)Ⅱ型糖尿病SD 大鼠(i.g.400 mg/kg CYP),Ⅱ型糖尿病Wistar 大鼠(i.g.100 mg/kg CYP)提高代謝酶活性(HK↑、SDH↑),調(diào)節(jié)糖脂代謝紊亂(TC↓、TG↓、LDL-C↓、MDA↓、HDL-C↑);降低空腹血糖,增加胰島素敏感性(bcl-2↑、胰島細(xì)胞存活率↑、胰島功能↑),改善胰島素分泌(INSR↑、IRS-1↑、PI-3K↑),升高胰島素,降低胰高血糖素[10],[33],[48]~[51]尿囊素 鏈脲佐菌素誘導(dǎo)Ⅱ型糖尿病SD 大鼠(i.g.2 mg/kg 尿囊素)薯蕷皂苷 高膽固醇飲食誘導(dǎo)的高血脂SD 大鼠(質(zhì)量分?jǐn)?shù)0.5%的薯蕷皂苷),高血脂KM 小鼠、Wistar 大鼠(i.g.160,200 mg/kg 薯蕷皂苷)調(diào)節(jié)氧化應(yīng)激(SOD↑、GSH↑、MDA↓),促進(jìn)脂質(zhì)代謝 (TC↓、LDL↓、ALT↓、AST↓、LDH↓),保肝保腎(Cre↓、BUN↓、UA↓、ALP↓);保護(hù)胰島素和血糖水平(GLP-1↑,改善胰島β 細(xì)胞形態(tài)功能)減少膽固醇分泌(TC↓、血漿HDL↑),抑制吸收及微膠粒形成;緩解氧化應(yīng)激(SOD↑、CAT↑、淋巴細(xì)胞、紅細(xì)胞DNA 損傷↓);增加膽汁分泌,降膽固醇[51][52],[53]
山藥中的尿囊素具有抗氧化作用,能夠降低肌酐(Creatinine,Cre)、血尿素氮(Blood urea nitrogen,BUN)、尿酸(Uric acid,UA)、堿性磷酸酶(Alkaline phosphatase,ALP)等腎臟功能相關(guān)酶活性,保護(hù)肝臟和腎臟。并且改善胰島β 細(xì)胞形態(tài)功能,促進(jìn)胰高血糖素樣肽-1 (Glucagon like peptide-1,GLP-1)釋放,有效治療糖尿病[51]。
薯蕷皂苷在動(dòng)物水平上可以有效緩解高膽固醇飲食誘導(dǎo)的高膽固醇血癥。其作用機(jī)制為增加膽汁分泌,緩解氧化應(yīng)激引起的DNA 損傷,降低血漿和肝臟中TC 水平,從而抑制膽固醇吸收[52-53]。
2.5 抗氧化
體內(nèi)外實(shí)驗(yàn)證明,山藥具有抗氧化及抗衰老活性。如表6所示,CYP 具有還原性和自由基清除活性,可以下調(diào)促凋亡蛋白Bcl-2 相關(guān)X 蛋白(Bcl-2 assaciated X protein,Bax)水平[54-55]。此外,CYP 通過調(diào)節(jié)p53/p21 衰老基因相關(guān)通路,抑制神經(jīng)細(xì)胞缺氧性凋亡和大腸桿菌生長(zhǎng)[56]。數(shù)據(jù)顯示,CYP 呈劑量依賴型,可調(diào)節(jié)血清、肝、腦、心、脾等組織的氧化應(yīng)激,抑制脂質(zhì)過氧化(Lipid peroxidation,LPO),降低過氧化物酶(Peroxidase,POD)、活性氧(Reactive oxygen species,ROS)和三磷酸腺苷(Adenosine triphosphate,ATP)相關(guān)酶的活力水平[57]??寡趸瘷C(jī)制是通過清除自由基,調(diào)節(jié)系統(tǒng)相關(guān)酶活力,抑制衰老基因表達(dá)而實(shí)現(xiàn)。山藥低聚糖也能夠清除自由基,實(shí)現(xiàn)抗氧化功效[8]。
表6 山藥的抗氧化功能研究現(xiàn)狀
Table 6 Research status of antioxidation function of Chinese yam
注:CYOs.山藥低聚糖。
受試物 實(shí)驗(yàn)?zāi)P?作用效果及機(jī)制 參考文獻(xiàn)山藥多糖 C57BL/6 小鼠模型 (質(zhì)量分?jǐn)?shù)1%的薯[55]~[58]蕷皂苷),SD 胎鼠大腦皮層神經(jīng)細(xì)胞(0.05~0.1 g/L CYP),DPPH、ABTS 自由基清除實(shí)驗(yàn),F(xiàn)RAP 法測(cè)定總還原力(152.87,168.31,231.82 μg/mL CYP)具有還原性,顯著的自由基清除活性 (H2O2↓、DPPH↓、·OH↓、O2-↓),促凋亡/抗凋亡率下調(diào)(Bax↓、Bcl-2↑);調(diào)節(jié)系統(tǒng)抗氧化酶活力(SOD↑、CAT ↑、GSH-Px ↑、LPO ↓、POD ↓、ROS ↓、MDA↓)和ATP 酶活性(Na+/K+-ATP 酶↑、Mg2+-ATP 酶↑、腦系數(shù)↑);調(diào)節(jié)p53/p21 衰老相關(guān)通路,抑制神經(jīng)細(xì)胞缺氧性凋亡山藥低聚糖 ·OH 自 由 基 清 除 實(shí) 驗(yàn) (100 μg/mL CYOs)自由基清除活性(·OH↓、O2-↓) [8]山藥多酚 亞硝酸鹽體外清除實(shí)驗(yàn),鐵氰化鉀還原實(shí)驗(yàn),DPPH 自由基清除實(shí)驗(yàn),脂質(zhì)過氧化LPO 實(shí)驗(yàn)(0.4 g/L 山藥多酚)薯蕷皂苷 ISO 誘導(dǎo)的心肌梗塞Wistar 大鼠(p.o.10 mg/kg 薯蕷皂苷)抑制硝酸鹽還原酶活性;清除自由基,調(diào)節(jié)細(xì)胞內(nèi)氧化應(yīng)激(總多酚還原力↑、烷氧基↓、烷過氧化基↓、DPPH↓),抗脂質(zhì)過氧化提高抗氧化酶活性(GSH↑、SOD↑、CAT↑、GR↑);緩解紅細(xì)胞損傷,清除自由基(DPPH↓、·OH↓)[58],[59][60]
山藥中含有的多酚類物質(zhì)具備強(qiáng)還原性,其酚羥基既能與蛋白質(zhì)結(jié)合,又能與金屬離子發(fā)生螯合作用,并且可以清除體內(nèi)自由基,抗脂質(zhì)過氧化,調(diào)節(jié)胞內(nèi)氧化應(yīng)激[58-59]。
薯蕷皂苷對(duì)心肌梗塞模型鼠的治療與其抗氧化作用密切相關(guān),它通過提高GSH、SOD、CAT、GSH-Px、谷胱甘肽還原酶(Glutathione reductase,GR)的活性,減少紅細(xì)胞和淋巴細(xì)胞DNA 損傷,同時(shí)清除自由基,緩解氧化應(yīng)激[60]。
2.6 其它
除上述提到的營(yíng)養(yǎng)活性以外,山藥的功能還集中體現(xiàn)在抗腫瘤免疫[29],改善認(rèn)知,增肌,促進(jìn)愈合[61]以及雌激素樣作用[62]等方面,研究現(xiàn)狀如表7所示。
表7 山藥的其它營(yíng)養(yǎng)功能研究現(xiàn)狀
Table 7 Research status of other nutritional functions of Chinese yam
受試物(對(duì)應(yīng)功能) 實(shí)驗(yàn)?zāi)P?作用效果及機(jī)制 參考文獻(xiàn)薯蕷皂苷(抗腫瘤免疫)薯蕷皂苷(改善認(rèn)知、抗老化)尿囊素(雌激素樣作用)黑色素瘤C57BL/6 小鼠(i.g.20 mg/kg 薯蕷 皂 苷),AOM/DSS 誘 導(dǎo) 癌 癥ICR 小 鼠[p.o.(63.8±1.2)mg/kg 薯蕷皂苷元],結(jié)直腸癌HCT-116 和HT-29 細(xì)胞系(40 μmol/L 薯蕷皂苷)D-半乳糖誘導(dǎo)的衰老ICR 小鼠(p.o.125 mg/kg 薯 蕷 皂 苷);AD 轉(zhuǎn) 基 因 小 鼠(p.o.80 mg/kg 薯 蕷 皂 苷 元),LPS 誘 導(dǎo) 的C57BL/6 小鼠(p.o.25 mg/kg 薯蕷皂苷),卵 巢 切 除Wistar 大 鼠(p.o.100 mg/kg 薯蕷皂苷),人U251 膠質(zhì)瘤細(xì)胞、RAW264.7 細(xì)胞(200 ng/mL 薯蕷皂苷),人角質(zhì)化細(xì)胞(10-6 mol/L 薯蕷皂苷元)KM 小鼠子宮增重實(shí)驗(yàn)(i.g.0.02 g/mL 尿囊素),MCF-7 細(xì)胞增殖拮抗實(shí)驗(yàn)(1 μmol/L 雌激素受體、膜受體GPR30 阻斷劑)體內(nèi):改變腸道菌群的組成(乳酸菌Lactobacillus↑、薩特氏菌Sutterella↑、擬桿菌Bacteroides↓),提高抗腫瘤免疫活性 (T 細(xì)胞浸潤(rùn)↑、IFN-γ↑);體外:調(diào)整細(xì)胞增殖 (周期素D1),細(xì)胞凋亡(p38 MAPK 途徑、外源性細(xì)胞受體途徑、內(nèi)源性線粒體途徑、Akt 途徑),遷移和侵襲,氧化反應(yīng)(HO-1↑、SOD-3↑、caspase-6↑),激活STAT3 通路保護(hù)神經(jīng)(星形膠質(zhì)細(xì)胞激活↓),改善海馬5-HT代謝(5-羥基吲哚乙酸↑、L-色氨酸↑、吲哚乙醛↑);增強(qiáng)認(rèn)知(淀粉樣斑塊↓、神經(jīng)原纖維纏結(jié)↓、星形膠質(zhì)細(xì)胞↓、Tau 蛋白磷酸化↓),改善神經(jīng)免疫(IL-2↓)以及更年期認(rèn)知障礙;改善神經(jīng)炎癥(HMGB-1 / TLR4,TNF-α↓,IL-1β↓,NF-kB↓、MYD88↓);人類皮膚DNA 合成↑、溴脫氧尿苷攝取↑,cAMP↑發(fā)揮由ERα 和GPR30 介導(dǎo)的雌激素樣作用(E2↑、FSH↑)[62],[63],[69],[70][64],[66],[71],[72][61]尿囊素(改善肌膚,愈合傷口)深度燒傷后愈合患者 (復(fù)方肝素鈉尿囊素凝膠,早晚涂藥)促進(jìn)組織細(xì)胞再生,軟化角質(zhì)層蛋白 [67]
薯蕷皂苷對(duì)黑色素瘤細(xì)胞、結(jié)直腸癌、前列腺癌、乳腺癌、肝癌等多種癌細(xì)胞具有細(xì)胞毒性[62]。體外通過抑制腫瘤細(xì)胞增殖,誘導(dǎo)凋亡及氧化反應(yīng),發(fā)揮抗腫瘤作用;體內(nèi)可改變腸道菌群的組成,程序性死亡受體1 (Programmed cell death protein1,PD-1)抗體治療可增強(qiáng)這一功效,證明山藥能提高抗腫瘤免疫活性[63]。
除此之外,薯蕷皂苷能夠顯著改善衰老引起的認(rèn)知障礙,增強(qiáng)體內(nèi)抗氧化酶活力[64]。薯蕷皂苷處理能增強(qiáng)AD 小鼠的認(rèn)知功能,減少大腦皮層和海馬區(qū)淀粉狀斑塊和神經(jīng)元纖維節(jié),還可以外源激活1,25D3-MARRS/PDIA3/ERp57 通路,觸發(fā)軸突生長(zhǎng),靶向治療AD 等神經(jīng)退行性疾病[65]??估匣鞘硎氃碥招麻_發(fā)的功能活性,可以促進(jìn)人類皮膚DNA 合成,溴脫氧尿苷的攝取,提高細(xì)胞內(nèi)環(huán)磷酸腺苷cAMP 水平,說明薯蕷皂苷可以用于老化皮膚上角化細(xì)胞增殖修復(fù),且具有安全性[66]。
據(jù)報(bào)道,山藥中的尿囊素可以促進(jìn)未成熟小鼠子宮指數(shù)升高,增加雌二醇(Estradiol,E2)、促卵泡激素(Follicle-stimulating hormone,F(xiàn)SH)等雌性激素水平[61]。臨床數(shù)據(jù)顯示,尿囊素可以改善肌膚,促進(jìn)健康組織細(xì)胞再生,軟化角質(zhì)層蛋白,形成彈力的瘢痕表面,對(duì)魚鱗病、手足皸裂等多種皮膚病都有一定改善作用[67-68]。
總結(jié)上述文獻(xiàn)得出,山藥中活性成分能夠通過NF-κB、MAPK、AMPK、Akt、p53、Nrf2 等分子靶點(diǎn),影響下游基因表達(dá),調(diào)節(jié)細(xì)胞因子和氧化還原酶活力,清除自由基及過氧化物,改善血糖水平,發(fā)揮免疫、抗炎、調(diào)節(jié)糖脂代謝、抗氧化等作用。其具體的分子機(jī)制如圖2所示。
圖2 山藥營(yíng)養(yǎng)功能的作用機(jī)制
Fig.2 Molecular mechanism of nutritional function of Chinese yam
3 展望
綜上所述,山藥資源有巨大的經(jīng)濟(jì)價(jià)值,近年來,國(guó)內(nèi)外對(duì)山藥營(yíng)養(yǎng)功能的研究大部分集中于體外水平和動(dòng)物水平,山藥對(duì)人體生理的調(diào)節(jié)機(jī)制研究不甚明確[73]。山藥成分復(fù)雜,其特征組分結(jié)構(gòu)尚不清晰,未來應(yīng)該進(jìn)一步明確山藥多糖、多酚的結(jié)構(gòu)組成。此外,利用多組學(xué)技術(shù)闡明山藥活性成分對(duì)人體保健的作用機(jī)制,靶向干預(yù)各類慢性疾病,響應(yīng)“精準(zhǔn)營(yíng)養(yǎng)”的理念,將成為山藥營(yíng)養(yǎng)研究的主要趨勢(shì)。
目前,新型冠狀病毒肺炎(Novel coronavirus pneumonia,NCP)疫情依舊嚴(yán)峻,免疫力低下是易感人群的一大特征,NCP 主要侵犯的器官是肺和脾[74]。通過食療提升機(jī)體免疫力,從而達(dá)到預(yù)防NCP 的功效,不失為良策。山藥作為一種藥食同源食材,在中醫(yī)上常用于治療脾胃虛弱,食少倦怠、營(yíng)養(yǎng)不良、虛勞咳嗽等癥狀[2]。由此可見,將山藥開發(fā)成新型天然安全的免疫增強(qiáng)劑具有很大的研究?jī)r(jià)值。
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