Hypoglycemic and hypolipidemic effects of a polysaccharide from Lachnum YM240 and its derivatives in mice, induced by a high fat diet and low dose STZ

Abstract

Carboxymethylated and sulfated polysaccharides (CLEP and SLEP) were prepared from an exopolysaccharide previously obtained from YM240 (LEP) by chemical modifications. Two doses (50 mg kg and 200 mg kg b. w.) of LEP, CLEP and SLEP were orally administered to normal mice and type 2 diabetic mice (T2DM) that were induced by streptozotocin (STZ) and a high fat diet, respectively. The hypoglycemic effect was evaluated by testing the oral glucose tolerance, fasting blood glucose (FBG) levels, fasting serum insulin (FINS), glycosylated hemoglobin A1c (HbA1c), and the hypolipidemic effect was evaluated by the body, spleen, pancreas, liver and kidney weights, as well as serum triglycerides (TG), cholesterol (TC) and free fatty acids (FFA). After four weeks of administration, LEP, CLEP and SLEP showed a marked FBG fall rate of 11.2%, 44.0% and 42.5% for the high-dose and 7.43%, 38.5% and 33.1% for the low-dose, respectively, as compared to the DC group. Moreover, compared with DC mice, TC concentrations in the high-dose groups of LEP, CLEP and SLEP were significantly decreased by 29.6%, 38.7% ( < 0.05), 33.0% ( < 0.05), and TG concentrations decreased by 18.9%, 43.9% ( < 0.01), 29.0% ( < 0.05), respectively. In addition, LEP and the derivatives significantly upregulated the expression of glucokinase (GK) and adenosine monophosphate-activated protein kinase (AMPK) in the liver, AMPK and glucose transporter 4 (Glut4) in skeletal muscle and peroxysome proliferator-activated receptor (PPAR-γ) in adipose tissue, whereas downregulated the expression of glucose-6-phosphatase (G6P) in the liver; these were examined using ELISA detection kits. These results for FBG and serum lipids indicate that LEP and its derivatives possess significant hypoglycemic and hypolipidemic effects and carboxymethylation improved the hypoglycemic and hypolipidemic effects more effectively than sulfation. Therefore, the carboxymethylated and sulfated modifications were effective ways to enhance the hypoglycemic and hypolipidemic activities of polysaccharides.

Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice

“…To continue, we also reported a drop in liver GCK expression, which correlates well with one previous investigation [49]. By comparison, other reports have observed the upregulation of hepatic GCK following the intake of a polysaccharide extract [64] and a fermented product [57] in diabetic and HFD-fed mice, respectively. Our finding suggests a reduced glycolysis or glucose utilization in the liver, which would lead to greater circulating glucose levels, as well as a compromised insulin secretion [58].…”

Hypolipidaemic and antioxidant capacities of polysaccharides obtained from Laminaria japonica by different extraction media in diet‐induced mouse model

“…Thus, such a process is safe for food and pharmaceutical manufacturing. The doses of LJPC used in this study were comparable to those of polysaccharide extracts used in rodent model studies (Zha et al, 2012;Wang et al, 2017). However, it remains unclear how a maximum safe dose evaluated using experimental animals can be converted the human dose, although some studies proposed the conversion could be achieved by multiplying a conversion factor, for example a factor of 0.162 (considering the ratio of animal body weight to human body weight) (FDA, 2005) or 0.018 (considering both the ratios of body weight and body surface area between animal to human) (Reagan-Shaw et al, 2008).…”

“…Thus, LJPC could possess dosedependent hypolipidaemic capacity, and the modes of action underlying might include the inhibition of HDL oxidation at a high dose and suppression of the uptake of oxidised LDL at a medium dose (Aviram et al, 1998;Fuhrman et al, 2002). The doses of LJPC used in this study were comparable to those of polysaccharide extracts used in rodent model studies (Zha et al, 2012;Wang et al, 2017). A long-term high-fat diet likely induces several lipid metabolism disorders (Tian & Yu, 2015).…”

Efficacy of a Methanolic Extract of Adansonia digitata Leaf in Alleviating Hyperglycemia, Hyperlipidemia, and Oxidative Stress of Diabetic Rats

“…It might be one of the reasons leading to intestinal absorption reduction attributive in the hypoglycaemic effect. Furthermore, important ingredients of the extract, saponins [ 27 ] and mucilage [ 28 ], have been reported to have a strong hypoglycemic effect in the diabetic rats. Also, Rajkumar et al [ 29 ] have suggested that the extract reduced weight gain in the diabetic rats which might be due to an elevated rate of catabolism leading to muscle loss.…”