Phloridzin ameliorates type 2 diabetes-induced depression in mice by mitigating oxidative stress and modulating brain-derived neurotrophic factor.

Purpose: Type 2 diabetes (T2D) is linked with depression due to insulin resistance, oxidative stress and disruption of neurotrophic factors. We evaluated potential benefits of phloridzin in ameliorating depressive symptoms in T2D.

Methods: Adult male Swiss-albino mice (25-30 g) on high-fat-diet (HFD) for 2 weeks were administered with streptozotocin (STZ; 35 mg/kg, intraperitoneal) to induce T2D. Seven days after STZ administration, diabetic mice on HFD were distributed into different groups. Animals were subjected daily to oral treatment of saline (0.25 ml), fluoxetine (10-20 mg/kg) or phloridzin (10-20 mg/kg) for a period of 4 weeks. One hour after last dose, the immobility time of animals was evaluated in forced swim test (FST) and tail suspension test (TST). To further confirm the mechanisms involved in antidepressant effect of phloridzin, biochemical parameters like brain derived neurotropic factor (BDNF), glutathione (GSH), extracellular signal-regulated kinase (ERK), tyrosine receptor kinase B (TrkB) and cAMP-response element binding protein (CREB) were estimated in the brain.

Results: Animals with T2D showed a significant increase in immobility as compared to control in FST and TST. However, 4 weeks administration of fluoxetine or phloridzin attenuated this effect. A significant decline in GSH, BDNF, TrkB, CREB and ERK levels were noticed in the brain of mice with T2D. These changes were also attenuated by administration of phloridzin.

Conclusions: Phloridzin may ameliorates T2D-induced depression by mitigating the oxidative stress, and up-regulation of neurotrophins in the brain. Therefore, phloridzin can be used as a therapeutic intervention for the management of depression co-morbid with T2D.