桑叶多糖治疗糖尿病机制的研究进展
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摘要
全球范围内糖尿病及高血脂等代谢性疾病的发病率逐年增高,大部分2型糖尿病患者需终身用药,不仅医疗负担重,且有药物不良反应,造成严重的健康、经济问题。研发更加有效的降糖药物是目前的研究热点,尤其是从天然植物中提取有效成分。近几年的研究发现桑叶多糖降糖效果确切且来源广泛、易获取。本文就桑叶多糖降糖、调脂、抗氧化、抑制β细胞凋亡、调节胰岛素信号通路、抑制α-糖苷酶、调节肠道菌群及延缓糖尿病肾病发生发展等几方面机制的研究进展进行综述。
The incidence of metabolic diseases such as diabetes and hyperlipidemia in the world is increasing year by year. Most patients with type 2 diabetes need life-long medication,which not only bright huge medical burden,but also have side effects,causing serious health and economic problems. The development of more effective hypoglycemic drugs is the current research focus,especially the extraction of active ingredients from natural plants. In recent years,the study found anti-diabetic effects of polysaccharide from mulberry leaf is accurate,the source is widely. In this paper,the mulberry leaf polysaccharide exhibits multiple therapeutic effects,including blood glucose and blood lipid lowering,antioxidant,insulin sensitivity-improving,α-glycosidase-inhibiting,intestinal flora-regulating and diabetic nephropathy-protecting were summarized research progress on the aspects of mechanism.
The incidence of metabolic diseases such as diabetes and hyperlipidemia in the world is increasing year by year. Most patients with type 2 diabetes need life-long medication,which not only bright huge medical burden,but also have side effects,causing serious health and economic problems. The development of more effective hypoglycemic drugs is the current research focus,especially the extraction of active ingredients from natural plants. In recent years,the study found anti-diabetic effects of polysaccharide from mulberry leaf is accurate,the source is widely. In this paper,the mulberry leaf polysaccharide exhibits multiple therapeutic effects,including blood glucose and blood lipid lowering,antioxidant,insulin sensitivity-improving,α-glycosidase-inhibiting,intestinal flora-regulating and diabetic nephropathy-protecting were summarized research progress on the aspects of mechanism.
引文
[1]RIBOLA F A,CANCADO F B,SCHOUERI J H,et al.Effects of SGLT2 inhibitors on weight loss in patients with type 2 diabetes mellitus[J].Eur Rev Med Pharmacol Sci,2017,21(1):199-211.
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[3]季涛,宿树兰,郭盛,等.桑叶防治糖尿病的效应成分群及其作用机制研究进展[J].中草药,2015,46(5):778-784.
[4]LEAHY J L,HIRSCH I B,PETERSON K A,et al.Targeting betacell function early in the course of therapy for type 2 diabetes mellitus[J].J Clin Endocrinol Metab,2010,95(9):4206-4216.
[5]POITOUT V,ROBERTSON R P.Glucolipotoxicity:Fuel excess andβ-cell dysfunction[J].Endocrine Rev,2008,29(3):351.
[6]陈建国,步文磊,来伟旗,等.桑叶多糖降血糖作用及其机制研究[J].中草药,2011,42(3):515-520.
[7]路国兵,任春久,崔为正,等.桑叶多糖MLPⅡ的基本结构及对糖尿病模型大鼠的降血糖作用[J].蚕业科学,2011,37(6):1053-1060.
[8]LIU C G,MA Y P,ZHANG X J.Effects of mulberry leaf polysaccharide on oxidative stress in pancreaticβ-cells of type 2 diabetic rats[J].Eur Rev Med Pharmacol Sci,2017,21(10):2482-2488.
[9]文静,张德芹,黄春丽,等.桑叶提取物对MSG肥胖大鼠脂代谢的影响及其机制[J].中国实验方剂学杂志,2015,21(14):111-115.
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[11]路国兵,任春久,崔为正,等.桑叶多糖MLPⅡ对糖尿病模型大鼠肝脏胰岛素抵抗的改善作用[J].蚕业科学,2012,38(1):116-121.
[12]REDDY V P,ZHU X,PERRY G,et al.Oxidative stress in diabetes and Alzheimer’s disease[J].J Alzheimers Dis,2015,16(4):763-774.
[13]LI Y G,JI D F,ZHONG S,et al.Hybrid of 1-deoxynojirimycin and polysaccharide from mulberry leaves treat diabetes mellitus by activating PDX-1/insulin-1 signaling pathway and regulating the expression of glucokinase,phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in alloxa[J].J Ethnopharmacol,2011,134(3):961-970.
[14]YUAN Q,XIE Y,WEI W,et al.Extraction optimization,characterization and antioxidant aactivity in vitro,of polysaccharides from mulberry(Morus alba,L.)leaves[J/OL].Carbohydrate Polym,2015,128:e52-e62.2015-04-21[2018-06-22].https://www.sciencedirect.com/science/article/pii/S0144861715003379?via%3Dihub.
[15]龚云,沈兴珠,张鑫,等.桑叶粗多糖对糖尿病大鼠糖代谢及脑组织氧化应激的影响[J].西北师范大学学报(自然科学版),2011,47(4):98-101.
[16]任春久,孙永亮,李伟庆,等.桑叶多糖MLPⅡ对糖尿病大鼠胰腺组织氧化应激的保护作用[J].蚕业科学,2017,43(4):671-676.
[17]于泽奇,程世翔,涂悦,等.Ki-67、Bcl-2、Bax和Caspase-3在脑胶质瘤组织中的表达及临床意义[J].中国医药导报,2017,14(5):9-12.
[18]ZHANG Y,REN C,LU G,et al.Anti-diabetic effect of mulberry leaf polysaccharide by inhibiting pancreatic islet cell apoptosis and ameliorating insulin secretory capacity in diabetic rats[J].Int Immunopharmacol,2014,22(1):248-257.
[19]ZHANG Y,REN C,LU G,et al.Purification,characterization and anti-diabetic activity of a polysaccharide from mulberry leaf[J].Regul Toxicol Pharmacol,2014,70(3):687-695.
[20]IYPE T,FRANCIS J,GARMEY J C,et al.Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1:application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes[J].J Biol Chem,2005,280(17):16798-16807.
[21]GERBER P A,RUTTER G A.The role of oxidative stress and hypoxia in pancreatic beta-cell dysfunction in diabetes mellitus[J].Antioxid Redox Signal,2017,26(10):501-518.
[22]REN C,ZHANG Y,CUI W,et al.A polysaccharide extract of mulberry leaf ameliorates hepatic glucose metabolism and insulin signaling in rats with type 2 diabetes induced by high fat-diet and streptozotocin[J/OL].Int J Biol Macromol,2015,72:e951-e959.2015-01-01[2018-06-22].https://www.sciencedirect.com/science/article/pii/S0141813014006746?via%3Dihub.
[23]SALTIEL A R,KAHN C R.Insulin signalling and the regulation of glucose and lipid metabolism[J].Nature,2001,414(6865):799-806.
[24]方飞,吴新荣,罗明俐,等.HepG2细胞胰岛素抵抗模型的建立及在筛选桑叶有效部位中的应用[J].医药导报,2012,31(6):691-694.
[25]FANG F,LUO M L,NAN S U,et al.Effect of mulberry leaves extracts on glucose uptake of insulin-resistant HepG2 cells and the mechanism[J].Acta Pharmaceutica Sinica,2012,47(11):1452-1456.
[26]刘洪凤,韩智学,赵正林,等.桑叶多糖对2型糖尿病大鼠GLUT4 mRNA表达的影响[J].中国食物与营养,2012,18(3):68-69.
[27]SEELY B L,STAUBS P A,REICHART D R,et al.Protein tyrosine phosphatase 1B interacts with the activated insulin receptor[J].Diabetes,1996,45(10):1379-1385.
[28]季涛,宿树兰,郭盛,等.基于α-葡萄糖苷酶抑制活性评价桑叶多组分药效相互作用研究[J].中国中药杂志,2016,41(11):1999-2006.
[29]韩爱芝,王丽君,贾清华,等.药桑叶多糖提取工艺优化及其降血糖活性研究[J].中国酿造,2017,36(8):139-143.
[30]LARSEN N,VOGENSEN F K,BERG F W J V D,et al.Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults[J].PLoS One,2010,5(2):9085.
[31]陈涟昊,张霞,孙世芳,等.桑叶多糖调节小鼠肠道菌群失调的研究[J].现代药物与临床,2015,30(6):633-636.
[32]黄立佳,杜月光,孙梽均,等.桑叶黄酮和多糖对糖尿病大鼠血清肿瘤坏死因子-α、C反应蛋白含量及肾功能的影响[J].中国老年学杂志,2016,36(19):4703-4705.
[33]韩智学,薛继婷,李齐,等.桑叶多糖对糖尿病肾病大鼠AdipoR1表达的影响[J].中国食物与营养,2014,20(11):74-75.
[34]LI W,CUI M,WEI Y,et al.Inhibition of the expression of TGF-β1and CTGF in human mesangial cells by exendin-4,a glucagon-like peptide-1 receptor agonist[J].Cell Physiol Biochem,2012,30(3):749-757
[35]HENDARTO H,INOGUCHI T,MAEDA Y,et al.GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases[J].Metabolism,2012,61(10):1422-1434.
[36]宋铁军,李齐,薛继婷,等.桑叶多糖对DN大鼠肾脏CTGF表达的影响[J].中国食物与营养,2014,20(8):73-75.
[37]张雨薇,薛继婷,李齐,等.桑叶多糖对DN大鼠的保护作用及机制研究[J].中华中医药学刊,2016,34(6):1381-1383.
[2]INTERNATIONAL DIABETES FEDERATION(IDF).IDF Diabetes Atlas[M].8th edition.Brussels:IDF,2017:25.
[3]季涛,宿树兰,郭盛,等.桑叶防治糖尿病的效应成分群及其作用机制研究进展[J].中草药,2015,46(5):778-784.
[4]LEAHY J L,HIRSCH I B,PETERSON K A,et al.Targeting betacell function early in the course of therapy for type 2 diabetes mellitus[J].J Clin Endocrinol Metab,2010,95(9):4206-4216.
[5]POITOUT V,ROBERTSON R P.Glucolipotoxicity:Fuel excess andβ-cell dysfunction[J].Endocrine Rev,2008,29(3):351.
[6]陈建国,步文磊,来伟旗,等.桑叶多糖降血糖作用及其机制研究[J].中草药,2011,42(3):515-520.
[7]路国兵,任春久,崔为正,等.桑叶多糖MLPⅡ的基本结构及对糖尿病模型大鼠的降血糖作用[J].蚕业科学,2011,37(6):1053-1060.
[8]LIU C G,MA Y P,ZHANG X J.Effects of mulberry leaf polysaccharide on oxidative stress in pancreaticβ-cells of type 2 diabetic rats[J].Eur Rev Med Pharmacol Sci,2017,21(10):2482-2488.
[9]文静,张德芹,黄春丽,等.桑叶提取物对MSG肥胖大鼠脂代谢的影响及其机制[J].中国实验方剂学杂志,2015,21(14):111-115.
[10]SOLINAS G,NAUGLER W,GALIMI F,et al.Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates[J].Proc Natl Acad Sci U S A,2006,103(44):16454-16459.
[11]路国兵,任春久,崔为正,等.桑叶多糖MLPⅡ对糖尿病模型大鼠肝脏胰岛素抵抗的改善作用[J].蚕业科学,2012,38(1):116-121.
[12]REDDY V P,ZHU X,PERRY G,et al.Oxidative stress in diabetes and Alzheimer’s disease[J].J Alzheimers Dis,2015,16(4):763-774.
[13]LI Y G,JI D F,ZHONG S,et al.Hybrid of 1-deoxynojirimycin and polysaccharide from mulberry leaves treat diabetes mellitus by activating PDX-1/insulin-1 signaling pathway and regulating the expression of glucokinase,phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in alloxa[J].J Ethnopharmacol,2011,134(3):961-970.
[14]YUAN Q,XIE Y,WEI W,et al.Extraction optimization,characterization and antioxidant aactivity in vitro,of polysaccharides from mulberry(Morus alba,L.)leaves[J/OL].Carbohydrate Polym,2015,128:e52-e62.2015-04-21[2018-06-22].https://www.sciencedirect.com/science/article/pii/S0144861715003379?via%3Dihub.
[15]龚云,沈兴珠,张鑫,等.桑叶粗多糖对糖尿病大鼠糖代谢及脑组织氧化应激的影响[J].西北师范大学学报(自然科学版),2011,47(4):98-101.
[16]任春久,孙永亮,李伟庆,等.桑叶多糖MLPⅡ对糖尿病大鼠胰腺组织氧化应激的保护作用[J].蚕业科学,2017,43(4):671-676.
[17]于泽奇,程世翔,涂悦,等.Ki-67、Bcl-2、Bax和Caspase-3在脑胶质瘤组织中的表达及临床意义[J].中国医药导报,2017,14(5):9-12.
[18]ZHANG Y,REN C,LU G,et al.Anti-diabetic effect of mulberry leaf polysaccharide by inhibiting pancreatic islet cell apoptosis and ameliorating insulin secretory capacity in diabetic rats[J].Int Immunopharmacol,2014,22(1):248-257.
[19]ZHANG Y,REN C,LU G,et al.Purification,characterization and anti-diabetic activity of a polysaccharide from mulberry leaf[J].Regul Toxicol Pharmacol,2014,70(3):687-695.
[20]IYPE T,FRANCIS J,GARMEY J C,et al.Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1:application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes[J].J Biol Chem,2005,280(17):16798-16807.
[21]GERBER P A,RUTTER G A.The role of oxidative stress and hypoxia in pancreatic beta-cell dysfunction in diabetes mellitus[J].Antioxid Redox Signal,2017,26(10):501-518.
[22]REN C,ZHANG Y,CUI W,et al.A polysaccharide extract of mulberry leaf ameliorates hepatic glucose metabolism and insulin signaling in rats with type 2 diabetes induced by high fat-diet and streptozotocin[J/OL].Int J Biol Macromol,2015,72:e951-e959.2015-01-01[2018-06-22].https://www.sciencedirect.com/science/article/pii/S0141813014006746?via%3Dihub.
[23]SALTIEL A R,KAHN C R.Insulin signalling and the regulation of glucose and lipid metabolism[J].Nature,2001,414(6865):799-806.
[24]方飞,吴新荣,罗明俐,等.HepG2细胞胰岛素抵抗模型的建立及在筛选桑叶有效部位中的应用[J].医药导报,2012,31(6):691-694.
[25]FANG F,LUO M L,NAN S U,et al.Effect of mulberry leaves extracts on glucose uptake of insulin-resistant HepG2 cells and the mechanism[J].Acta Pharmaceutica Sinica,2012,47(11):1452-1456.
[26]刘洪凤,韩智学,赵正林,等.桑叶多糖对2型糖尿病大鼠GLUT4 mRNA表达的影响[J].中国食物与营养,2012,18(3):68-69.
[27]SEELY B L,STAUBS P A,REICHART D R,et al.Protein tyrosine phosphatase 1B interacts with the activated insulin receptor[J].Diabetes,1996,45(10):1379-1385.
[28]季涛,宿树兰,郭盛,等.基于α-葡萄糖苷酶抑制活性评价桑叶多组分药效相互作用研究[J].中国中药杂志,2016,41(11):1999-2006.
[29]韩爱芝,王丽君,贾清华,等.药桑叶多糖提取工艺优化及其降血糖活性研究[J].中国酿造,2017,36(8):139-143.
[30]LARSEN N,VOGENSEN F K,BERG F W J V D,et al.Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults[J].PLoS One,2010,5(2):9085.
[31]陈涟昊,张霞,孙世芳,等.桑叶多糖调节小鼠肠道菌群失调的研究[J].现代药物与临床,2015,30(6):633-636.
[32]黄立佳,杜月光,孙梽均,等.桑叶黄酮和多糖对糖尿病大鼠血清肿瘤坏死因子-α、C反应蛋白含量及肾功能的影响[J].中国老年学杂志,2016,36(19):4703-4705.
[33]韩智学,薛继婷,李齐,等.桑叶多糖对糖尿病肾病大鼠AdipoR1表达的影响[J].中国食物与营养,2014,20(11):74-75.
[34]LI W,CUI M,WEI Y,et al.Inhibition of the expression of TGF-β1and CTGF in human mesangial cells by exendin-4,a glucagon-like peptide-1 receptor agonist[J].Cell Physiol Biochem,2012,30(3):749-757
[35]HENDARTO H,INOGUCHI T,MAEDA Y,et al.GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases[J].Metabolism,2012,61(10):1422-1434.
[36]宋铁军,李齐,薛继婷,等.桑叶多糖对DN大鼠肾脏CTGF表达的影响[J].中国食物与营养,2014,20(8):73-75.
[37]张雨薇,薛继婷,李齐,等.桑叶多糖对DN大鼠的保护作用及机制研究[J].中华中医药学刊,2016,34(6):1381-1383.