Yukun Jiao1, Xueqian Wang2, Xiang Jiang2, Fansheng Kong2, Shumei Wang3, Chunyan Yan4. 1. 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. 2. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. 3. 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. 4. 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.
Abstract
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 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:Diabeticrats 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 diabeticrats. 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 diabeticrats. 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.
Authors: Bisma Jan; Rabea Parveen; Sultan Zahiruddin; Mohammad Umar Khan; Sradhanjali Mohapatra; Sayeed Ahmad Journal: Saudi J Biol Sci Date: 2021-03-31 Impact factor: 4.219