Polysaccharide from Hovenia dulcis (Guaizao) improves pancreatic injury and regulates liver glycometabolism to alleviate STZ-induced type 1 diabetes mellitus in rats.

Hovenia dulcis is a traditional medicinal and edible plant and has a major geographical presence in China. In this study, a polysaccharide purified from H. dulcis (HDPs-2A) was found to ameliorate type 1 diabetes mellitus (T1DM) in streptozotocin-induced diabetic rat. HDPs-2A treatment resulted in significantly lower fasting blood glucose levels, but higher body weight, plasma insulin, and liver glycogen levels. Moreover, HDPs-2A improved dyslipidemia, pancreatic oxidative stress, and reduced serum pro-inflammatory factors. In addition, HDPs-2A up-regulated PDX-1, activated and up-regulated IRS2 expression, and regulated apoptosis and regeneration of islet β cells to recover islet β-cell function injury in TIDM rats. HDPs-2A also up-regulated the expression of pancreatic GK and GLUT2 to improve insulin secretion ability of islet β-cells, ultimately improving the glucose metabolism disorder of T1DM rats. Moreover, HDPs-2A significantly up-regulated the expression of GK and down-regulated the expression of G6Pase in liver to improve liver glycogen synthesis, inhibit liver gluconiogenesis, and improve liver glucose metabolism disorder of T1DM rats. In summary, the hypoglycemic mechanisms of HDPs-2A may include regulating the regeneration and apoptosis of islet β-cells and activating liver glycometabolism-related signaling pathways in T1DM rats.

Yang B ，Luo Y ，Wei X ，Kan J ... -  《-》

Isolation, purification, structural characterization, and hypoglycemic activity assessment of polysaccharides from Hovenia dulcis (Guai Zao).

Hovenia dulcis polysaccharides (HDPs) have a variety of important biological activities associated with potential applications in food engineering, pharmacy science, and health care. Herein, we isolated and purified polysaccharides from H. dulcis. Chemical composition analysis revealed that the purified polysaccharides (HDPs-2A) were composed of different molar ratios of mannose, Rha, GalA, GlcA, Glc, Gal, and Ara and had a molecular weight of 372.91 kDa. The structure of HDPs-2A was assessed by FT-IR, periodate oxidation, Smith degradation, methylation analysis, and NMR, allowing us to determine that the backbone of HDPs-2A is composed primarily of →5)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →6)-β-D-Galp-(1→, →3,6)-β-D-Galp-(1→, T-β-D-Galp, →3)-β-D-Galp-(1→, and T-α-D-Glcp. The results of atomic force microscopy (AFM) showed that HDPs-2A present an irregular polymer particle morphology in water. X-ray diffraction (XRD) results showed that HDPs-2A have a single crystal structure. Finally, we demonstrated that HDPs-2A have a good therapeutic effect on a rat model of type 2 diabetes.

Yang B ，Luo Y ，Sang Y ，Kan J ... -  《-》

Hypoglycemic effect of low-sugar juice derived from Hovenia dulcis on type 1 diabetes mellitus rats.

Fruit juice is usually rich in monosaccharides and disaccharides. A reverse osmosis separation machine was used to remove monosaccharides and disaccharides from Hovenia dulcis fruit juice, leaving behind most of the bioactive substances in a low-sugar fruit juice (LSFJ), so as to provide a more effective treatment for diabetic patients. This study was carried out with type 1 diabetes mellitus model induced with high dose of streptozotocin (60 mg kg-1 ), and oral administration of LSFJ for 4 weeks. LSFJ treatment led to significant gain in body weight and increased serum insulin level, insulin-like growth factor-1 level, blood urea nitrogen level, creatinine level, and hepatic glycogen level. Meanwhile, fasting blood glucose, fructosamine level, and glucose tolerance were also observably enhanced. Additional, LSFJ treatment significantly improved lipid metabolism, islet quality, and islet oxidative stress. The messenger RNA levels of glucose metabolism genes in the pancreas of diabetic rats decreased in the diabetes model group, whereas messenger RNA expression of these genes was significantly increased with LSFJ treatment. These findings indicate that LSFJ can improve symptoms associated with type 1 diabetes mellitus. The research also suggests new strategies for diabetes prevention and treatment. © 2021 Society of Chemical Industry.

Yang B ，Wei X ，Luo Y ，Kan J ... -  《-》

Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice.

Rehmannia glutinosa (Gaertn.) DC. (RG) has been widely used as traditional Chinese herbal medicine for treatment of diabetes and its complications. The polysaccharide fraction of RG has been proposed to possess hypoglycemic effect by intraperitoneal administration, however, the mechanisms responsible for the hypoglycemic effect of RG polysaccharide (RGP) remain poorly understood. Here we studied the anti-hyperglycemic and anti-hyperlipidemic effect of oral administration of a purified RGP and its underlying mechanisms in streptozotocin (STZ)-induced diabetic mice. The preliminary structure of RGP was determined by GC and FT-IR. Mice were injected with STZ to induce type 1 diabetes. RGP at doses of 20, 40 and 80 mg/kg/day was orally administered to mice for 4 weeks, and metformin was used as positive control. After 4 weeks, the blood biochemical parameters, the pancreatic insulin contents, in vitro insulin secretion, the hepatic glycogen contents and mRNA expression of phosphoenolpyruvate carboxyl kinase (PEPCK) were assayed. RGP was composed of rhamnose, arabinose, mannose, glucose and galactose in the molar ratio of 1.00:1.26:0.73:16.45:30.40 with the average molecular weight of 63.5 kDa. RGP administration significantly decreased the blood levels of glucose, total cholesterol, triglycerides, low density lipoprotein-cholesterol, and increased the blood levels of high density lipoprotein-cholesterol and insulin in diabetic mice, concurrent with increases in body weights and pancreatic insulin contents. The in vitro study revealed that RGP significantly enhanced both basal and glucose-stimulated insulin secretions, as well as islet insulin contents in the pancreatic islets of diabetic mice. Moreover, RGP reversed the increased mRNA expression of PEPCK and the reduced glycogen contents in the liver of diabetic mice. Furthermore, RGP exhibited potent anti-inflammatory and anti-oxidative activities, as evidenced by the decreased blood levels of TNF-α, IL-6, monocyte chemoattractant protein-1, MDA, and also the elevated blood levels of SOD and GPx activities in diabetic mice. Taken together, RGP can effectively ameliorate hyperglycemia, hyperlipemia, vascular inflammation and oxidative stress in STZ-induced diabetic mice, and thus may be a potential therapeutic option for type 1 diabetes.

Zhou J ，Xu G ，Yan J ，Li K ，Bai Z ，Cheng W ，Huang K ... -  《-》

High-pressure ultrasonic-assisted extraction of polysaccharides from Hovenia dulcis: Extraction, structure, antioxidant activity and hypoglycemic.

In this study, high-pressure ultrasonic-assisted extraction (HUE) technology was used for polysaccharide extraction from Hovenia dulcis (HDPS). A maximal extraction yield (11.81 ± 0.26%) was obtained using the response surface method (RSM) with optimized HUE conditions (Ultrasound power 330 W, 68 °C, and 22 min). Results showed that HDPS mainly contained neutral sugar (47.81 ± 1.56%), uronic acid (12.52 ± 0.15%), and protein (3.64 ± 0.24%), specifically. HDPS was comprised of mannose, rhamnose, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 3.20%, 20.40%, 4.81%, 11.14%, 27.37% and 33.08%, respectively. And with an average molecular weight of 185.22 kDa for its major component (accounting for 90.13% for HDPS). The result obtained from the X-ray diffraction pattern confirmed a semi-crystalline nature of the sample. HUE-HDPS suggested typical shear thinning behavior and non-Newtonian properties. Additionally, HUE-HDPS exhibited better chemical antioxidant activities in DPPH, ABTS, hydroxyl radical scavenging and Fe2+ chelation activity. The in-vitro and in-vivo experiments indicated that HUE-HDPS had obviously hypoglycemic effects. Accordingly, the polysaccharides from Hovenia dulcis might serve as a natural antioxidant and hypoglycemic agent.

Yang B ，Wu Q ，Luo Y ，Yang Q ，Wei X ，Kan J ... -  《-》