桑叶多糖对高脂饮食联合链脲佐菌素诱导的 2 型糖尿病大鼠的降糖作用。
Antidiabetic effects of Morus alba fruit polysaccharides on high-fat diet- and streptozotocin-induced type 2 diabetes in rats.
机构信息
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China; Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, China; Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
出版信息
J Ethnopharmacol. 2017 Mar 6;199:119-127. doi: 10.1016/j.jep.2017.02.003. Epub 2017 Feb 2.
ETHNOPHARMACOLOGICAL RELEVANCE
Type 2 diabetes mellitus (T2DM) is becoming a serious threat to human health. The fruit of Morus alba L. is widely used as a traditional Chinese medicine for the treatment of DM, dizziness, tinnitus, insomnia, and premature graying, as well as to protect the liver and kidneys. Several studies have demonstrated that the aqueous extracts of the roots bark, leaves, and ramuli of mulberry, which are known to contain polyphenols and polysaccharides, have antihyperglycemic and antihyperlipidemic activities. The aim of the present study was to further investigate the active polysaccharides from M. alba fruit by evaluating the antidiabetic activities of different fractions on T2DM rats and elucidate the mechanism underlying these activities.
MATERIALS AND METHODS
Diabetic rats were treated with two fractions of M. alba fruit polysaccharides (MFP50 and MFP90). The disease models were induced by a high-fat diet and low dose injection of streptozotocin and were compared to normal rats and metformin-treated diabetic rats. After seven weeks, the fasting blood glucose (FBG), oral glucose tolerance test (OGTT), fasting serum insulin (FINS) levels, homeostasis model of assessment-insulin resistance (HOMA-IR), glycated serum protein (GSP), and serum alanine transaminase (ALT) levels, as well as serum lipid profiles and histopathological changes in the pancreas were measured. Next, the expressions of the insulin signaling pathway were measured by western blot analysis to elucidate the potential mechanism underlying these antidiabetic activities.
RESULTS
After seven weeks of treatment, a significant reduction in the FBG levels, OGTT-area under the curve (OGTT-AUC), FINS, HOMA-IR, ALT, and triglyceride (TG) values of the MFP50 group was observed. On the other hand, in the MFP90 group, the FBG, OGTT-AUC, FINS, HOMA-IR, GSP, and TG levels were significantly reduced. The level of high-density lipoprotein cholesterol (HDL-c) and the proportion of HDL-c to total cholesterol (TC) significantly increased in the MFP50 group. Moreover, MFP50 and MFP90 induced repair of damaged pancreatic tissues of the diabetic rats. The hypoglycemic effect of MFP50 was more stable than MFP90, whereas the hypolipidemic effect of MFP90 was slightly better than MFP50. Moreover, the expression levels of InsR, IRS-2, Akt and GLUT4 in the MFP90 group significantly increased relative to that of the T2DM group.
CONCLUSIONS
MFP50 and MFP90 have markedly antihyperglycemic and antihyperlipidemic effects and can clearly relieve diabetes symptoms in the T2DM rat model. The M. alba fruit polysaccharides may potentially be utilized as an effective treatment for T2DM. Further research into the structures of active M. alba fruit polysaccharides and their mechanisms in promoting antidiabetic effects are underway.
ETHNOPHARMACOLOGICAL 相关性:2 型糖尿病(T2DM)正成为人类健康的严重威胁。桑椹的果实被广泛用作治疗糖尿病、头晕、耳鸣、失眠和早白以及保护肝肾的中药。几项研究表明,已知含有多酚和多糖的桑树根皮、叶和嫩枝的水提物具有降血糖和降血脂活性。本研究旨在通过评估不同部位对 T2DM 大鼠的抗糖尿病活性,进一步研究桑椹中的活性多糖,并阐明这些活性的机制。
材料和方法
糖尿病大鼠用两种桑椹果多糖(MFP50 和 MFP90)进行治疗。通过高脂肪饮食和低剂量链脲佐菌素注射诱导疾病模型,并与正常大鼠和二甲双胍治疗的糖尿病大鼠进行比较。七周后,测量空腹血糖(FBG)、口服葡萄糖耐量试验(OGTT)、空腹血清胰岛素(FINS)水平、胰岛素抵抗评估的稳态模型(HOMA-IR)、糖化血清蛋白(GSP)和血清丙氨酸氨基转移酶(ALT)水平,以及血清血脂谱和胰腺组织学变化。然后,通过 Western blot 分析测量胰岛素信号通路的表达,以阐明这些抗糖尿病活性的潜在机制。
结果
治疗七周后,MFP50 组 FBG 水平、OGTT-曲线下面积(OGTT-AUC)、FINS、HOMA-IR、ALT 和三酰甘油(TG)值显著降低。另一方面,在 MFP90 组中,FBG、OGTT-AUC、FINS、HOMA-IR、GSP 和 TG 水平均显著降低。MFP50 组高密度脂蛋白胆固醇(HDL-c)水平和 HDL-c 与总胆固醇(TC)的比例显著升高。此外,MFP50 和 MFP90 诱导糖尿病大鼠受损胰腺组织修复。MFP50 的降血糖作用比 MFP90 更稳定,而 MFP90 的降血脂作用略优于 MFP50。此外,MFP90 组 InsR、IRS-2、Akt 和 GLUT4 的表达水平与 T2DM 组相比显著增加。
结论
MFP50 和 MFP90 具有明显的降血糖和降血脂作用,可明显缓解 T2DM 大鼠模型的糖尿病症状。桑椹多糖可能有望作为 T2DM 的有效治疗方法。目前正在对活性桑椹多糖的结构及其促进抗糖尿病作用的机制进行进一步研究。