Ethanol extract of Alpiniae oxyphyllae fructus regulates glucose metabolism, the HPA axis and hippocampal function in diabetic mice with depression

Abstract Background: Alpiniae oxyphyllae fructus (AOF) is the dry ripe fruit of Alpinia oxyphylla Miq . which has significant therapeutic effects in Alzheimer's disease, Parkinson's disease, depression, learning and memory dysfunction and other nervous system disease. Methods: In this study, we established a mouse model of Type 2 Diabetes Mellitus (T2DM) combined with depression induced by feeding high fat and high sugar diet combined with intraperitoneal injection of streptozotocin (STZ) and chronic unpredictable mild stress (CUMS) to evaluate the dual therapeutic effects of ethanol extract of AOF (EEA), and further explore the mechanism of EEA on diabetes complicated with depression. Results: The results showed that EEA improved the body weight of diabetic mice with depression (DD mice). EEA could also improve glucose metabolism and insulin resistance in DD mice. Next, EEA improved the depression-like behaviors of DD mice. EEA also attenuated diabetes and CUMS-induced hyperactivity of the hypothalamic-pituitary-adrenal(HPA) axis and improved the expression of neurotransmitters and synaptic plasticity in the hippocampus of DD mice. In addition, EEA could improve hippocampal tissue damage caused by neuroinflammation and oxidative stress. Further research showed that EEA improved the protein expression and phosphorylation of Phosphoinositide 3-kinase (PI3K), Protein kinase B (Akt) and Mammalian target of rapamycin (mTOR) in the hippocampus of DD mice. Conclusions: This study showed that EEA may have a dual role in the treatment of diabetes and depression and provided new scientific theoretical basis for the future development of AOF and the prevention and treatment of diabetes complicated with depression.