Natural diterpenoid alysine A isolated from Teucrium alyssifolium exerts antidiabetic effect via enhanced glucose uptake and suppressed glucose absorption

Teucrium species have been used in folk medicine as antidiabetic, antiinflammatory, antiulcer, and antibacterial agents. We have explored in vitro antidiabetic impacts of 2 natural diterpenoids, alysine A and alysine B, isolated from Teucrium alyssifolium. The lactate dehydrogenase (LDH) cytotoxicity assay, glucose uptake test, glucose utilization (glycogen content) test, glucose transport test, glucose absorption (α-glucosidase activity) test, insulin secretion test, RNA isolation and cDNA synthesis assay, qPCR quantification assays, and statistical analyses were carried out in the present study. Alysine A exerted the following effects at non-cytotoxic doses: • Enhanced the glucose uptake, as much as the insulin in the C2C12, HepG2, and 3T3-L1 cells • Increased the glycogen content in the C2C12 and HepG2 liver cells, significantly higher than the insulin and metformin • Suppressed the alpha-glucosidase and the GLUT2 expression levels in the Caco-2 cells • Suppressed the SGLT1 and GLUT1-5 expression levels in the Caco-2 cells • Induced the insulin receptor substrate (IRS)1 and GLUT2 expression levels of the BTC6 pancreatic cells • Induced the insulin receptor (INSR), IRS2, phosphoinositide 3-kinase (PI3K), GLUT4, and protein kinase (PK) expression levels of the 3T3-L1 and C2C12 cells • Increased glucose transport through the Caco-2 cell layer • Did not influence insulin secretion in the pancreatic BTC6 cells Consequently, these data strongly emphasized the antidiabetic action of alysine A on the particularly critical model mechanisms that assume a part in glucose homeostasis, such as glucose uptake, utilization, and storage. Moreover, the expression level of the essential genes in glucose metabolism and insulin signaling was altered in a way that the results would be antihyperglycemic. A blend of in vitro and in situ tests affirmed the antihyperglycemic action of alysine A and its mechanism. Alysine A has exercised significant and positive results on the glucose homeostasis; thus, it is a natural and pleiotropic antidiabetic agent. Advanced in vivo studies are required to clarify the impact of this compound on glucose homeostasis completelyThis work was supported by the Scientific and Technological Research Council of Turkey under TÜBİTAK, under Project No.: 114Z640, and Pamukkale University under Project No.: PAUBAP-2014FBE029

Epilobium hirsutum alters xenobiotic metabolizing CYP1A1, CYP2E1, NQO1 and GPx activities, mRNA and protein levels in rats

Context: Natural products have attracted increasing interests due to their use in flavoring, nutrition, cosmetics, pharmacy and medicine. Epilobium hirsutum L. (Onagraceae) is known for its analgesic, antimicrobial, and antiproliferative activity. CYP1A1 and CYP2E1, xenobiotic metabolizing enzymes, serve as a metabolic activation route yielding reactive metabolites that are eliminated by the action of NQO1 and glutathione peroxidase (GPx) enzymes. Objective: This study investigated in vivo effects of Epilobium hirsutum (EH) on CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA expressions in liver. Materials and methods: Male Wistar Albino rats were injected with EH at a dose of 37.5mg/kg i.p. daily for 9d. CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA levels were determined by enzyme assays, Western blotting and qPCR, respectively. Results: CYP1A1 associated ethoxyresorufin-O-deethylase activity of control and EH-treated animals were found as 6.54±1.21 and 4.48±1.67nmol/min/mg, respectively. CYP2E1 associated aniline 4-hydroxylase of control and EH group were 0.537±0.011 and 0.109±0.01nmol/min/mg, respectively. However, EH treatment increased the GPx and NQO1 activities from 0.069±0.015 to 0.107±0.026nmol/min/mg and from 163.34±92 to 588.3±14nmol/min/mg, respectively. Furthermore, protein and mRNA expression analysis revealed that CYP1A1 and CYP2E1 levels were decreased while those of NQO1 and GPx increased after EH treatment. Discussion and conclusion: Our current data suggest that the metabolism of xenobiotics, including drugs, may be altered due to changes in the expression and activity of these proteins by EH. © 2013 Informa Healthcare USA, Inc

Yakıotunun Ksenobiyotik Metabolizması Üzerine Etkilerinin ve İlaç-Diyet Etkileşim Potansiyelinin Proteomik ve Moleküler Yaklaşımlar ile Aydınlatılması

TÜBİTAK TBAG Proje15.05.201

Investigation of aromotase inhibition by several dietary vegetables in human non-small cell lung cancer cell lines

Objective: In this study we have investigated the effect of extracts obtained from well-known vegetable diets consumed commonly in Mediterranean and Aegean regions of Turkey on the expression of aromatase at protein, mRNA and activity levels in human non-small cell lung cancer cells- PC-3 and PC-14 cell lines. Method: For this purpose, cytotoxicity was determined by using crystal violet stain. In vivo and in vitro aromatase activity was determined flourometrically. The expression of aromatase in protein and mRNA levels was detected by Western blotting using anti-hCYP19 and reverse transcriptase- polymerase chain reaction using suitable primers, respectively. Result: Extracts obtained from Laurus nobilis, Mentha piperita, Crocus sativus reduced aromatase activity 32%, 44%, 36% and 42%, 32%, 56% in PC-14 and PC-3 cell lines, respectively, no significant changes were observed in protein and mRNA levels. Whereas extract obtained from Allium porrum decreased aromatase activity and mRNA level only in PC-14 cell lines by 52% and 2,5-fold, respectively, without significant influence on aromatase protein level. Conclusion: The results obtained in this study have shown that Laurus nobilis, Mentha piperita, Crocus sativus and Allium porrum do contain effective aromatase inhibitors. Therefore, further studies investigating the content of these vegetables are necessary to understand the potential role and mechanism of action of these foods in reducing the risk of non-small cell lung carcinomas. © TurkJBiochem.com