LAUSR

Abstract Artemisia sphaerocephala Krasch polysaccharide (ASKP) has previously been reported to ameliorate the hyperglycemia and oxidative stress in type 2 diabetes mellitus and was separated into two fractions of 60P and 60S. To determine the major functional fraction in ASKP, the antidiabetic effects of ASKP and its two fractions were investigated in diabetic db/db mice. As a result, 60P showed the highest and 60S showed the lowest capability in many aspects: decreasing the fasting blood glucose, glycated serum protein, and the insulin resistance in db/db mice; reversing the dyslipidemia caused by diabetes as indicated by the decreased levels of total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and non-esterified fatty acid; as well as exerting antioxidant activities (increases in catalase, superoxide dismutase, and glutathione peroxidase, and a decrease in malondialdehyde) and hepatoprotective activities (increases in total protein and albumin, decreases in alanine aminotransferase and aspartate aminotransferase) in the liver of db/db mice. Liver histopathological observation, using both hematoxylin-eosin staining and periodic acid-Schiff reagent staining, indicated that all polysaccharide fractions could ameliorate the deterioration of hepatic lesions and increase the hepatic glycogen storage in db/db mice. Furthermore, analysis of relative mRNA expression levels suggested that all polysaccharide fractions promoted the glycogen synthesis by up-regulating the expressions of peroxisome proliferator-activated receptor-γ, glucose transporter-4, phosphoinositide 3-kinase, protein kinase B, and glucokinase and inhibited gluconeogenesis via down-regulating the expression of phosphoenopyruvate carboxykinase. Overall, 60P showed as the major antidiabetic fraction in ASKP.