Search

Red Liriope platyphylla (RLP) manufactured by two repeated steps (steaming and drying) stimulates the insulin secretion ability and glucose receptor signaling pathway in an animal model for type I diabetes. This study examined the levels of glucose and lipid metabolism-related factors in a useful animal model for type II diabetes with obesity following RLP treatment for 3 weeks to determine if RLP treatment affects the glucose concentration, insulin secretion and fatty acid oxidation. The following results were obtained: i) RLP contained a large amount of polyphenolic compounds; ii) insulin secretion was induced in RLP-treated OLETF rats, although there were no significant differences in body weight, glucose tolerance test and glucose concentration; iii) the RLP-treated OLETF rats showed a significant increase in adiponectin concentration but the concentration of triglyceride and LDL decreased compared to the vehicle-treated rats; iv) although the abdominal fat mass and adipocyte size did not change with RLP treatment, expression of the adipocyte marker genes and β-oxidation genes in fat tissue was recovered to the level of the LETO rats; v) fatty liver formation was reduced dramatically in the liver of the RLP-treated group compared to the vehicle-treated group; vi) the expression of adipocyte marker genes and the β-oxidation gene in the liver tissue were generally similar to those of the abdominal fat but PPAR-γ showed a reverse pattern in the RLP- and vehicle-treated OLETF rats. These results suggest that RLP may stimulate insulin secretion and a decrease in lipid in serum, and may also suppress fatty liver formation through the regulation of fatty acid oxidation. The data presented here highlight the possibility that RLP can be considered a candidate for the prevention or alleviation of obesity-related diseases.

The present study was conducted to investigate whether the high antioxidant activity induced by selenium (Sel) treatment and selenoprotein M (SelM) overexpression affected the protein profile of the brain cortex. To accomplish this, the changes in global protein expression were measured in transgenic (Tg) rats expressing human SelM (CMV/hSelM) and non‑Tg rats using two-dimensional electrophoresis (2-DE). The results revealed that: ⅰ) CMV/hSelM Tg rats showed a high level of enzyme activity for antioxidant protein in the brain cortex compared to non-Tg rats; ⅱ) the high activity of these enzymes induced a decrease in total antioxidant concentration and γ-secretase activity in CMV/hSelM Tg rats; ⅲ) five proteins were upregulated and three were downregulated by SelM overexpression; ⅳ) among the five upregulated proteins, two associated with creatine kinase B-type (B-CK) and E3 ubiquitin-protein ligase RING1 (RING finger protein 1) were further increased in the two groups following Sel treatment, whereas synaptotagmin-15 (SytXV), eukaryotic translation initiation factor 4H (eIF-4H) and lactate dehydrogenase B (LDH-B) were increased or decreased under the same conditions; ⅴ) the three downregulated proteins did not induce a significant change in expression following Sel treatment; and ⅵ) the protein expression level alterations of the two selected spots (B-CK and SytXV) identified by 2-DE were extremely similar to the results from western blot analysis. Overall, the results of the present study provide primary novel biological evidence that new functional protein groups and individual proteins in the brain cortex of CMV/hSelM Tg rats are associated with Sel biology, including the response to Sel treatment and SelM overexpression.

Pen-2 is a key regulator of the γ-secretase complex, which is involved in the production of the amyloid β (Aβ)-42 peptides, which ultimately lead to Alzheimer's disease (AD). While Pen-2 has been studied in vitro, Pen-2 function in vivo in the brains of transgenic (Tg) mice overexpressing human Pen-2 (hPen-2) protein has not been studied. This study aimed to determine whether Pen-2 overexpression could regulate the AD-like phenotypes in Tg mice. NSE/hPen-2 Tg mice were produced by the microinjection of the NSE/hPen-2 gene into the pronucleus of fertilized eggs. The expression of the hPen-2 gene under the control of the NSE promoter was successfully detected only in the brain and kidney tissue of NSE/hPen-2 Tg mice. Also, 12-month-old NSE/hPen-2 Tg mice displayed behavioral dysfunction in the water maze test, motor activity and feeding behavior dysfunction in food intake/water intake/motor activity monitoring system. In addition, tissue samples displayed dense staining with antibody to the Aβ-42 peptide. Furthermore, NSE/hPen-2 Tg mice exhibiting feeding behavior dysfunction were significantly more apt to display symptoms related to diabetes and obesity. These results suggest that Pen-2 overexpression in NSE/hPen-2 Tg mice may induce all the AD-like phenotypes, including behavioral deficits, motor activity and feeding behavior dysfunction, Aβ-42 peptide deposition and chronic disease induction.

Synaptophysin is a synaptic vesicle glycoprotein involved in the regulation process for neurotransmitter release, which is distributed throughout neuroendocrine cells and all neurons in the brain and spinal cord. In an effort to determine whether amyloid β (Aβ)-42 peptides could influence the quantity and biochemical properties of synaptophysin, alterations in the levels of the synaptophysin protein in various soluble fractions were detected in the brains of four genotypes of transgenic mice (Tg) including Non-Tg, neuron-specific enolase (NSE)-hPS2m, NSE-hAPPsw and hAPPsw/hPS2m double Tg mice. Among the four genotypes of Tg mice, the highest levels of Aβ-42 peptides were noted in hAPPsw/hPS2m, followed by NSE-hAPPsw, NSE-hPS2m and Non-Tg mice. In the brains of these mice displaying different levels of Aβ-42 peptides, the levels of soluble synaptophysin were reduced significantly only in the hAPPsw/hPS2m double Tg mice compared to the Non-Tg mice. However, immunohistochemical analysis revealed no differences in the levels of total synaptophysin protein between the neocortex and hippocampus of the four different genotypes of mice. Western blot analysis using four-step fractions with differing solubility revealed a marked decrease in synaptophysin levels in the Tris-buffer saline fraction of hAPPsw/hPS2m double Tg mice and a significant increase in the formic acid fraction, relative to the Non-Tg mice. The results obtained from our in vivo experiments in mice are identical to the results observed in SK-N-MC cells treated with 100 nM Aβ-42 peptides. Therefore, our experiments collectively suggest that Aβ-42 peptides may alter the solubility without changing the total amount of synaptophysin.

The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant increase in glucose levels and a decrease of insulin concentration in the blood of mice, while their body weight remained constant over 5 days. The expression level of Glut-3 was down-regulated in the liver, or maintained at the same level in the brain of LP9MH80-H-treated mice. These changes corresponded to the phosphorylation of the p38 protein rather than to ERK and JNK in the MAPK signaling pathway. In addition, the expression level of Glut-1 increased significantly after LP9MH80-H treatment of both insulin target tissues in mice. Western blot analysis showed that Akt in the PI3-K pathway mainly participated in Glut-1 biosynthesis. Thus, these results suggest the possibility that the LP9M80-H-induced regulation of Glut-1 and Glut-3 biosynthesis may be mediated by the Akt and p38 MAPK signaling of the insulin signaling pathway in the liver and brain of mice.