Antidiabetic effects of Morus alba fruit polysaccharides on high-fat diet- and streptozotocin-induced type 2 diabetes in rats.
BACKGROUND
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.


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.
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.
Yukun
Y
Jiao
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Xueqian
X
Wang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Xiang
X
Jiang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Fansheng
F
Kong
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.
Shumei
S
Wang
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. Electronic address: ycybridge@163.com.
Chunyan
C
Yan
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D005638:Fruit; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D008297:Male; D031625:Morus; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use; D011134:Polysaccharides / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D010936:Plant Extracts; D011134:Polysaccharides; D013311:Streptozocin
Antidiabetic activity; Antihyperlipidemia; Citric acid (PubChem CID: 22230); Eosin Y (PubChem CID: 11048); Ethanol (PubChem CID: 702); Glucose (PubChem CID: 107526); Glycerol (PubChem CID: 753); Hematoxylin (PubChem CID: 10603); Methanol (PubChem CID: 887); Morus alba L.; Mulberry; Polysaccharides; Streptozotocin (PubChem CID: 29327); Trisodium citrate dehydrate (PubChem CID: 71474); Tween-20 (PubChem CID: 443314); Type 2 diabetic rats