Antihyperglycemic and Antilipidemic Effects of the Ethanol Extract Mixture of Ligularia fischeri and Momordica charantia in Type II Diabetes-Mimicking Mice.

Hyun Jin Baek,Jeong Eun Kwon,Jong Sung Ra,Se Chan Kang,Yong Joon Jeong,Sung Ryul Lee

doi:10.1155/2018/3468040

Abstract

The extract of the Momordica charantia fruit (MCE) is recognized as an alternative treatment for diabetes. The extract of Ligularia fischeri leaves (LFE) is traditionally used as a folk medicine for treating inflammatory diseases in Korea as well. In this study, we investigated the synergistic effect of MCE combined with LFE on antihyperglycemic and antihyperlipidemic potentials. Based on the α-glucosidase inhibitory effect and promotion of adipocyte differentiation in the 3T3-L1 cell line, the MLM was prepared with MCE:LFE (8:2 weight:weight). MLM showed the synergistic effects in the promotion of the glucose uptake rate, suppression of dipeptidyl peptidase-4 (DPP-4) mRNA expression, upregulation of an insulin receptor substrate and glucose transporter type-4 expression, and an increase in insulin-associated signaling in C2C12 cells. In addition, the efficacy of peroxisome proliferator-activated receptor-γ agonism and glucose uptake rate by MLM supplementation was significantly enhanced in vitro. Then, the antihyperglycemic and antihyperlipidemic effects of MCE, LFE, and MLM at the dose of 50, 100, and 200 mg/kg/day (n = 6 per each group) were determined in streptozotocin (STZ)-insulted mice fed an atherogenic diet (ATH) for 4 weeks. In addition, MLM (50, 100, and 200 mg/kg/day, n = 5 per each group) was supplemented in ATH-fed db/db mice for 10 weeks. Compared with MCE or LFE alone, MLM supplementation led to a more significant reduction of glucose levels in both STZ/ATH and db/db/ATH mice as well as lowered lipid profiles in STZ/ATH mice. In addition, the stimulation of islet of Langerhans regeneration was more pronounced by MLM supplementation in both mice models. In conclusion, antihyperglycemic and antihyperlipidemic effects were strengthened by the combined extracts of L. fischeri and M. charantia (MLM) in diabetes-mimicking mice.

Highlights

Diabetes mellitus (DM) is a chronic metabolic disease characterized by high glucose levels due to insulin insufficiency resulting from the loss of pancreatic β-cell function, insulin tolerance, or both [1]
We suggest that unknown synergistic effects involving both α-glucosidase inhibition and promotion of adipocyte differentiation may have occurred when MCE and L. fischeri extract (LFE) were combined; this synergy may provide additional αglucosidase inhibitory activity and promotion of adipocyte differentiation, both of which are beneficial in controlling hyperglycemia and obesity
The protein expression levels of peroxisome proliferatoractivated receptor γ (PPARγ), GLUT4, and the phosphorylated forms of insulin receptor substrate (IRS) and Akt greatly increased with MLM treatment. These results suggest that MCE or LFE may have a low capacity for improving insulin sensitivity, but the combination of the two may have a synergistic effect on insulin sensitivity through activation of IRS and Akt, as well as upregulation of PPARγ and glucose transporter type-4 (GLUT-4) expression

Summary

Introduction

Diabetes mellitus (DM) is a chronic metabolic disease characterized by high glucose levels due to insulin insufficiency resulting from the loss of pancreatic β-cell function (type 1 DM), insulin tolerance (type 2 DM), or both [1]. Glucose metabolism disorders are common in obesity [4], and increased plasma nonesterified fatty acid (NEFA) levels are an important cause of obesity-associated insulin resistance and cardiovascular disease [5]. The first-line treatment for diabetes is glucose-lowering therapy targeting different aspects of glucose metabolism, including insulin sensitivity (e.g., Evidence-Based Complementary and Alternative Medicine metformin and thiazolidinediones), insulin secretion and bioactivity (e.g., sulfonylureas, glucagon-like peptide 1 [GLP1] analogues, dipeptidyl peptidase 4 [DPP-4] inhibitors, and insulin analogues), and modulation of blood glucose levels either by increased excretion (e.g., sodium–glucose cotransporter 2 inhibitors, SGLT2i) or by delaying onset following nutrient digestion (e.g., α-glucosidase inhibitors and amylin) [6]. There is no established remedy for DM, and therapeutic interventions have focused on reducing glucose levels and preventing or delaying complications through diet, physical activity, medication, regular screening, and treatment [1, 8]

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Conclusion