Cell Suspension Culture of Eriobotrya japonica Regulates the Diabetic and Hyperlipidemic Signs of High-Fat-Fed Mice

Abstract

Abstract:The present study investigates the anti-hyperlipidemic and antihyperglycemic effects and mechanism in high-fat (HF)-fed mice of cell suspension culture of Eriobotrya japonica (TA), which contains a great number of pentacyclic terpenoids. Firstly, C57BL/6J mice were randomly divided into two groups: the control (CON) group was fed with a lowfat diet (n = 9), whereas the experimental group was fed a 45% HF diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and was orally given TA or rosiglitazone or not for 4 weeks. Blood and visceral adipose tissue, liver tissue and skeletal muscle were examined. Treatment with TA reduced body weight gain, weights of white adipose tissue (WAT) (including epididymal, perirenal, mesenteric WAT and visceral fat), and hepatic triacylglycerol content significantly without affecting food intake in diet-induced diabetic mice. TA effectively prevented HF diet-induced increases in the levels of blood glucose, insulin, leptin and HOMA-IR index (p < 0.001, p < 0.05, p < 0.05, p < 0.01, respectively) and attenuated insulin resistance. Treatment with TA, adipocytes in the visceral depots showed a reduction in size. TA effectively significantly increased the protein contents of phosphorylation of AMPK-α (Thr172) both in liver and adipose tissue. It is shown that TA OPEN ACCESSMolecules 2013, 18 2727 exhibits hypolipidemic effect in HF-fed mice by decreasing gene expressions of fatty acid synthesis, including acyl-coenzyme A: diacylglycerol acyltransferase (DGAT) 2, which catalyzes the final step in the synthesis of triglycerides, and antidiabetic properties occurred as a result of decreased hepatic glucose production via phosphenolpyruvate carboxykinase (PEPCK) down-regulation, improved insulin sensitization and TA (at 1.0 g/kg dose) decreased expression of hepatic and adipose 11-β-hydroxysteroid dehydroxygenase (11β-HSD1) gene, which contributed in attenuating diabetic state. Futhermore, TA at doses of 0.5 and 1.0 g/kg had serum lipid-lowering action characterized by the inhibition of DGAT 1 expression. Thus, amelioration of diabetic and dyslipidemic state by TA in HFfed mice occurred by regulation of PEPCK, DGAT2 and AMPK phosphorylation.

Biological Activities of Extracts from Loquat (Eriobotrya japonica Lindl.): A Review

“…By using the high-fat (HF) diet-induced diabetic C57BL/6J mice model, the hypoglycemic effects of loquat extracts were also investigated [36,37]. Loquat leaf extract containing corosolic acid ( 2 ) and maslinic acid ( 9 ) significantly ameliorated the hyperglycemia, hyperleptinemia, and hyperinsulinemia in 45% HF diet C57BL/6J mice [36].…”

“…Loquat leaf extract containing corosolic acid ( 2 ) and maslinic acid ( 9 ) significantly ameliorated the hyperglycemia, hyperleptinemia, and hyperinsulinemia in 45% HF diet C57BL/6J mice [36]. Cell suspension cultures of loquat contain a great number of pentacyclic terpenoids including tormentic acid ( 14 ), corosolic acid ( 2 ), ursolic acid ( 1 ), maslinic acid ( 9 ), and oleanolic acid ( 8 ) [37]. Addition of such cell suspension extract to the HF diet mice resulted in the prevention of the increase in the levels of blood glucose, insulin, leptin and homeostasis model assessment for insulin resistance index in the HF-diet mice [37].…”

“…Cell suspension cultures of loquat contain a great number of pentacyclic terpenoids including tormentic acid ( 14 ), corosolic acid ( 2 ), ursolic acid ( 1 ), maslinic acid ( 9 ), and oleanolic acid ( 8 ) [37]. Addition of such cell suspension extract to the HF diet mice resulted in the prevention of the increase in the levels of blood glucose, insulin, leptin and homeostasis model assessment for insulin resistance index in the HF-diet mice [37]. By using the type 2 diabetic Otsuka Long–Evans Tokushima fatty (OLETF) rats and KK-A y mice as experimental models, the hypoglycemic effects of loquat seeds were studied and results showed that OLETF rats fed a diet with 10% powdered loquat seed resulted in consistently reduced blood glucose concentration and serum insulin level compared to the control group [28].…”

“…Loquat extracts have shown other bioactivities such as improvement of liver function [66,67], lung [68], renal [65] and neuronal cells [46], and also loquat extracts showed anti-obesity and hypolipidemic activity [36,37,69], anti-thrombotic potential [20], antiaging effects [70], anti-allergic [22], and antinociceptive activities [24], etc.…”

“…The pentacyclic terpenoids extracts of cell suspension culture of loquat showed anti-hyperlipidemic effects in HF diet mice since it reduced body weight gain, weights of white adipose tissue (WAT) (including epididymal, perirenal, mesenteric WAT and visceral fat), size of adipocytes in the visceral depots and hepatic triacylglycerol content [36,37]. Such anti-hyperlipidemic effects were correlated with increased protein phosphorylation of AMPK-α (Thr172) both in liver and adipose tissue, increased the adipose PPARγ and hepatic PPARα mRNA levels, and decreased gene expressions of fatty acid synthesis, including acyl-coenzyme A: diacylglycerol acyltransferase 2 [36,37].…”