孫士紅 孟丹 陳艷
隨著患病率的逐年升高,糖尿病已成為威脅人類健康的前列。近年來國內(nèi)外有關(guān)各種植物中天然降糖物質(zhì)的研究和開發(fā)也十分活躍,根據(jù)糖尿病病因,很多天然產(chǎn)物是通過以下環(huán)節(jié)來降低血糖水平:①直接使血糖升高的激素水平;②增加胰島素受體的數(shù)目和親和力,增加胰島素敏感性,改善胰島素抵抗;③改善糖代謝;④促進(jìn)葡萄糖轉(zhuǎn)運(yùn)及周圍組織、靶器官對糖的利用;⑤通過清除氧自由基、改善高凝狀態(tài)、抑制蛋白非酶糖化、抑制醛糖還原酶以及提高免疫力等途徑控制和延緩糖尿病及其并發(fā)癥的發(fā)展。
具有降糖作用的豆科植物表現(xiàn)為最明顯降糖的有:黃芪屬Astragalus,羊蹄甲屬Bauhinia,大豆屬glycine等。主要降糖成分為多糖、黃酮、生物堿和皂甙,本文對一些豆科植物的降糖成分及其可能機(jī)制進(jìn)行綜述。
黃芪(Astragalus membranaceus)根多糖APS,通過降低酪氨酸蛋白磷酸酶1B的表達(dá)和調(diào)節(jié)胰島素信號途徑,使糖尿病大鼠骨骼肌對胰島素敏感性增加[1]。胡盧巴(Trigonella foenum graecum)種子多糖,能夠降低糖尿病大鼠的血清中果糖胺,三酰甘油,膽固醇和LDL濃度,抑制Ⅱ型糖尿病的血小板凝集[2]。
羊蹄甲屬植物(Bauhinia candicans)葉的山奈酚-3-O-β-蘆丁糖甙明顯降低糖尿病兔的血糖和尿糖,并改善正常兔的糖耐量[3]。從(Bauhinia forficate)提取的葉山奈酚二鼠李糖甙降低正常和糖尿病大鼠的血糖,對糖尿病大鼠降糖的降糖效果更加顯著,還能夠抑制過氧化物酶活性,減少脂質(zhì)過氧化反應(yīng)[4]。另外,從(Bauhinia megalandra)提取的葉槲皮素等八種黃酮類物質(zhì),可以不同程度地影響大鼠肝臟葡萄糖-6-磷酸酶活性[5]。大豆Glycine三種異黃酮降低多肽類激素誘導(dǎo)下瘦型動物的血糖和血脂[6]。大豆異黃酮改善肥胖大鼠的脂類代謝,激活體外細(xì)胞過氧化物酶體增殖性激活受體,產(chǎn)生抗糖尿病效應(yīng)[7]。銀合歡(Leucaena leucocephala(Lam.)de Wait)種子總黃酮對四氧嘧啶(ALX),腎上腺素和葡萄糖誘導(dǎo)的高血糖小鼠均具有降低血糖作用[8]。野葛(Pueraria labata(Wild)Ohwi)根提取的葛根素活化了α-腎上腺素受體,增加 β-內(nèi)啡呔的分泌[9,10],增加 C2C12 細(xì)胞對放射性葡萄糖的吸收,降低哌唑嗪預(yù)處理的α1-腎上腺素受體的激活[11]。改善Ⅱ型糖尿病患者紅細(xì)胞膜彈性和血流狀況,提高Ⅱ型糖尿患者胰島素敏感性[12]。能夠促進(jìn)前脂肪細(xì)胞的分化,增加胰島素抵抗的脂肪細(xì)胞對葡萄糖的攝入,還能夠通過促進(jìn)PPARγ表達(dá)和抑制游離Ca2+在TNF-α誘導(dǎo)的上皮細(xì)胞中的積累,來抑制TNF-a誘導(dǎo)的編程性細(xì)胞死亡和增強(qiáng)上皮細(xì)胞的生存能力[13],證明葛根素是通過增加葡萄糖利用和轉(zhuǎn)運(yùn),改善胰島素抵抗和提高免疫力等途徑治療糖尿病。從苦骨(Sophora flavesena Ait)中分離得到的活性成分苦骨異黃酮苷F,能非競爭性地抑制腸道內(nèi)α-葡萄糖苷酶的活性,有效地減少腸道對葡萄糖的吸收,還能抑制醛糖還原酶的活性,進(jìn)而預(yù)防糖尿病并發(fā)癥白內(nèi)障和腎病的發(fā)生 [14]。
羽扇豆屬植物(Lupinus)的2-硫碳金雀花堿可以增加葡萄糖誘導(dǎo)的胰島細(xì)胞對胰島素的分泌,阻滯β細(xì)胞的KATP酶的敏感通道,促進(jìn)胰島素分泌[15]。
黃芪(Astragalus membranaceus)中的黃芪甲甙刺激正常大鼠類胰高血糖素肽-1(GLP-1)的分泌,增加胰島素分泌[16]。大豆屬(Glycine)的大豆皂苷具有很強(qiáng)的α-葡萄糖苷酶抑制作用[17]。野葛(Pueraria thunbergiana)花提取的槐花皂苷Ⅲ對高血糖大鼠具有抗凝血作用,抑制丙二醛和羥自由基的形成,降低黃嘌呤氧化酶,醛氧化酶的活性,增加SOD,谷胱甘肽過氧化物酶以及過氧化氫酶的含量,對抗氧化作用進(jìn)行了調(diào)節(jié)[18]。
除以上幾種天然產(chǎn)物外,甘草(Glycyrrhiza uralensis)中的香豆素,其作為過氧化物酶體增殖受體中的一種,明顯降低糖尿病KK-Ay小鼠血糖水平[19]。大豆(Glycine)松醇降低Ⅱ型糖尿患者空腹血糖,胰島素,果糖胺,HbA1c濃度,并穩(wěn)定胰島素抵抗指數(shù)。降低總膽固醇,LDL,LDL/HDL比例和血液的舒張和收縮壓,并且增加HDL含量[20]。家山黧豆(Lathyrus sativus)種子提取的肌醇磷酸聚糖(IPG)抑制體外蛋白激酶A導(dǎo)致的耳蝸前庭神經(jīng)節(jié)細(xì)胞增殖,使培養(yǎng)的肝瘤細(xì)胞中由Br-cAMP誘導(dǎo)的磷酸烯醇丙酮酸羧激酶mRNA的表達(dá)減少,模擬了胰島素的作用[21]。
[1]Wu Y,OuYang JP,Wu K,W ang Y,Zhou YF,Wen CY.Hypoglycem ic effect of A stragalus polysaccharide and its effect on PTP1B.J Acta Pharmaco l Sin,2005,26(3):345-352.
[2]Hannan JM,Rokeya B,F(xiàn)aruque O,Nahar N,Mosihuzzaman M,Azad Khan AK,Ali L.Effect of soluble dietary fibre fraction of Trigonella foenum graecum on glycemic,insulinemic,lipidemic and platelet aggregation status of Type 2 diabetic model rats.J Ethnopharmacology,2003,88:73-77.
[3]Fuentes O,Arancibia-Avila P,Alarcon J.Related Articles,Hypoglycemic activity of Bauhinia candicans in diabetic induced rabbits.Fitoterapia,2004,75(6):527-532.
[4]De Sousa E,Zanatta L,Seifriz I,Creczynski-Pasa TB,Pizzolatti MG,Szpoganicz B,Silva FR.Related Articles,Hypoglycemic effect and antioxidant potential of kaempferol-3,7-O-(alpha)-dirhamnoside from Bauhinia forficata leaves.J Nat Prod,2004,67(5):829-832.
[5]Estrada O,Hasegawa M,Gonzalez-Mujica F,Motta N,Perdomo E,Solorzano A,Mendez J,Mendez B,Zea EG.Related Articles,Evaluation of flavonoids from Bauhinia megalandra leaves as inhibitors of glucose-6-phosphatase system.Phytother Res,2005,19(10):859-863.
[6]Ali AA,Velasquez MT,Hansen CT,Mohamed AI,Bhathena SJ.Related Articles,Modulation of carbohydrate metabolism and peptide hormones by soybean isoflavones and probiotics in obesity and diabetes.J Nutr Biochem,2005,16(11):693-699.
[7]Mezei O,Banz WJ,Steger RW,Peluso MR,Winters TA,Shay N.Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells.J Nutr,2003,133(5):1238-1243.
[8]李學(xué)堅(jiān),家剛,振林,海濱.合歡種子總黃酮降血糖作用的實(shí)驗(yàn)研究.中國中藥雜志,2005,30(11):842-844.
[9]Chen WC,Hayakawa S,Yamamoto T,Su HC,Liu IM,Cheng JT.Mediation of beta-endorphin by the isoflavone puerarin to lower plasma glucose in streptozotocin-induced diabetic rats.Planta Med,2004,70(2):113-116.
[10]Hsu FL,Liu IM,Kuo DH,Chen WC,Su HC,Cheng JT.Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats.J Nat Prod,2003,66(6):788-792.
[11]Hsu HH,Chang CK,Su HC,Liu IM,Cheng JT.Stimulatory effect of puerarin on alpha1A-adrenoceptor to increase glucose uptake into cultured C2C12 cells of mice.Planta Med,2002,68(11):999-1003.
[12]劉蘊(yùn)玲,陳少華,陳秀彬.葛根素對Ⅱ型糖尿病人胰島素敏感性的影響.遼寧實(shí)用糖尿病雜志,2000,8(1):62-64
[13]Xu ME,Xiao SZ,Sun YH,Zheng XX,Ou-Yang Y,Guan C.,The study of anti-metabolic syndrome effect of puerarin in vitro.Life Sci,2005,77(25):3183-3196.
[14]黃秋云,施海潮.中藥苦骨的抗糖尿病活性研究.海峽藥學(xué),1998,10(1):9.
[15]Garcia Lopez PM,de la Mora PG,Wysocka W,Maiztegui B,Alzugaray ME,Del Zotto H,Borelli MI,Quinolizidine alkaloids isolated from Lupinus species enhance insulin secretion.Eur J Pharmacol,2004,504(1-2):139-142.
[16]江清林,李延軍,辛華.黃芪甲甙對胰島素,C肽分泌作用研究.黑龍江醫(yī)藥科學(xué),1999,22(3):24-27.
[17]全吉淑,尹學(xué)哲,工藤重光.大豆胚軸中大豆皂甙的提取及其對α-葡萄糖苷酶的抑制作用;食品研究與開發(fā),2006,27(10):4-7.
[18]Choi J,Shin MH,Park KY,Lee KT,Jung HJ,Lee MS,Park HJ.,Effect of kaikasaponin III obtained from Pueraria thunbergiana flowers on serum and hepatic lipid peroxides and tissue factor activity in the streptozotocin-induced diabetic rat.J Med Food,2004,7(1):31-37.
[19]Kuroda M,Mimaki Y,Sashida Y,Mae T,Kishida H,Nishiyama T,Tsukagawa M,Konishi E,Takahashi K,Kawada T,Nakagawa K,Kitahara M.Phenolics with PPAR-gamma ligand-binding activity obtained from licorice(Glycyrrhiza uralensis roots)and ameliorative effects of Glycyrin on Genetically Diabetic KK-Ay Mice.Bioorganic & Medicinal Chemistry Letters,2003,(13):4267-4272.
[20]Kim JI,Kim JC,Kang MJ,Lee MS,Kim JJ,Cha IJ.Related Articles,Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type II diabetes mellitus:a randomized controlled study.Eur J Clin Nutr,2005,59(3):456-458.
[21]Paneda C,Villar AV,Alonso A,Goni FM,Varela F,Brodbeck U,Leon Y,Varela-Nieto I,Jones DR.Purification and characterization of insulin-mimetic inositol phosphoglycan-like molecules from grass pea(Lathyrus sativus)seeds.Mol Med,2001,7(7):454-460.