Can Sesamin Alone or Cotheapy with Anti-DM Medicines Alleviate the Abnormal Intermediate Metabolites of Glucose and Fatty Acids, the Oxygen Consumption and Renal Fibrotic Progression?

Diabetic nephropathy (DN) is one of the leading cause of death in diabetic patients. Accumulation of many intermittent or end glycation products in the body from hyperglycemia will induce imbalance of oxygen metabolism, renal hypoxia and production of reactive oxygen radicals, upregulated HIF-1 and related downstream target genes, such as glucose transporter-1…etc. Contemporary therapeutic strategy for DM is based on multitarget therapy, however none of them can avoid the fate of renal fibrogenesis. Although most of them are safe for renal function, hypoglycemia always can occur when glomerular filtration is reduced afterwards. Hence alternatives are required. Literature has indicated that sesamin exhibits anti-oxidative, anti-hypertensive, anti-hyperlipidemic, endothelial cell protective, endothelial nitric oxide synthase and nitric oxide modulatory effects. Considering the probable role of sesamin to improve the oxygen consumption capability, we raise the three-year project: In the first-year subproject, we will investigate the in vitro effect of these abnormal metabolic intermediates on oxygen consumption, HIF-1 expression, and the protein expressions associated with renal fibrogenesis. In the second year, the sesamin intervention with all abnormal intermediates as indicated will be tested in vitro to explore the role of NO/Endothelin/Angiotensin and VEGF for improvement of the pathobiochemical changes as mentioned in the text and the modulation of the oxygen consumption and suppression of EMT. In the third year subproject, T2DM SD rat model will be established using high fat diet with STZ. The sesamin, either used alone or in cotherapy with the DM medicines as indiated, will be administered for three months. The level of abnomal metabolic intermediates, renal oxygen consumption rate, vessel dynamic related factors, vascular density, and the degree of renal fibrogensesis will be estimated. The potential preventive effect of sesamin and its cotherapy on DN will be evaluated and to be used as the clinical therapeutic reference.