Paper Title
Fenugreek Seed Extract (FSE) and 4-Hydroxyisoleucine (4oh) Induce Sirt3-Mediated Antioxidant Effects in Diabetic C57bl/6 Mice Brain Tissue in Vivo

Abstract
Diabetes is a detrimental metabolic disorder, associated with oxidative stress and mitochondrial dysfunction in the brain. This study was designed to evaluate the antihyperglycemic and antioxidant (AO) potential of Fenugreek seed extract (FSE) and 4-hydroxyisolecuine (4OH) in Normoglyceamic and Streptozotocin (STZ)-induced diabetic C57BL/6 mice brain tissue. Following a 10-day STZ (50mg/kg BW) diabetic induction, and 15-day FSE (100mg/kg BW) and 4OH (100mg/kg BW) treatment, the OGTT test revealed decreased blood glucose levels in diabetic mice, exhibiting their hypoglycaemic ability. Both FSE and 4OH displayed AO potential by increasing PGC-1α, phospho- and total Nrf2, Sirt3, and Pink1 protein levels. Furthermore, transcription of AMPKα1, Sirt3, NQO1, SOD1, and SOD2 genes were induced in treated mice brain tissue. In conclusion, we propose a mechanism by which FSE and 4OH exert hypoglycaemic effects in the brain through AO related mitochondrial responses. Index Terms— Sirtuin 3, diabetes, antioxidant, brain