Drug Design, Development and Therapy (Aug 2020)
Beneficial Effect of Genistein on Diabetes-Induced Brain Damage in the ob/ob Mouse Model
Abstract
Rong-zi Li,1 Xiao-Wen Ding,1 Thangiah Geetha,1 Layla Al-Nakkash,2 Tom L Broderick,2 Jeganathan Ramesh Babu1 1Department of Nutrition, Dietetics and Hospitality Management, Auburn University, Auburn, AL 36849, USA; 2Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USACorrespondence: Jeganathan Ramesh BabuDepartment of Nutrition, Dietetics and Hospitality Management, Auburn University, Auburn, AL 36849, USATel +1 334 844 3840 Fax +1 334 844 3268Email [email protected]: Diabetes mellitus (DM)-induced brain damage is characterized by cellular, molecular and functional changes. The mechanisms include oxidative stress, neuroinflammation, reduction of neurotrophic factors, insulin resistance, excessive amyloid beta (Aβ) deposition and Tau phosphorylation. Both antidiabetic and neuroprotective effects of the phytoestrogen genistein have been reported. However, the beneficial effect of genistein in brain of the ob/ob mouse model of severe obesity and diabetes remains to be determined.Methods: In this study, female ob/ob mice and lean control mice were fed with either a standard diet or a diet containing genistein (600mg/kg) for a period of 4 weeks. Body weight was monitored weekly. Blood was collected for the measurement of glucose, insulin and common cytokines. Mice brains were isolated for Western immunoblotting analyses.Results: Treatment with genistein reduced weight gain of ob/ob mice and decreased hyperglycemia compared to ob/ob mice fed the standard diet. The main findings show that genistein treatment increased insulin sensitivity and the expression levels of the neurotrophic factors nerve growth factor (NGF) and brain-derived neurotrophic factors (BDNF). In these mice, genistein also reduced Aβ deposition and the level of hyper-phosphorylated Tau protein.Conclusion: The results of our study indicate the beneficial effects of genistein in the obese diabetic mouse brain, including improving brain insulin signaling, increasing neurotrophic support, and alleviating Alzheimer’s disease-related pathology.Keywords: isoflavones, leptin-deficient mice, brain injury, insulin signaling, amyloid beta
