Human placental extract, melsmon, suppresses stress-induced neuroinflammation and peripheral inflammation in a mouse model of depression.

Neuroinflammation and hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis triggered by stress have been implicated in the pathophysiology of depression, highlighting the need for novel therapeutic approaches targeting these mechanisms. Placental extracts have been reported in clinical studies to alleviate fatigue and depressive symptoms, suggesting their potential to modulate stress-induced neuroinflammatory responses and HPA-axis activation, although this has not been adequately investigated. In this study, we used a stress-sensitive depression model mouse (SITH-1 mouse), which expresses the human herpesvirus 6 (HHV-6)-derived protein SITH-1 specifically in astrocytes, and subjected it to mild stress via water immersion cage stress (WICS) to induce inflammatory cytokine expression in the brain and peripheral organs. We further examined the effects of intramuscular administration of the human placental extract "Melsmon" (20 μL per injection, administered every other day for four doses) on neuroinflammation and HPA-axis hyperactivity in this model. As a result, WICS exposure led to increased expression of inflammatory cytokines in the brain and in peripheral organs such as the liver, colon, and heart, along with elevated expression of steroidogenic acute regulatory protein (StAR), a marker of HPA-axis activation, in the adrenal gland. These changes were suppressed by Melsmon treatment. Collectively, our findings suggest that Melsmon exerts anti-inflammatory effects in both central and peripheral tissues, potentially contributing to the stabilization of the HPA axis and attenuation of stress-related inflammatory responses involved in the pathogenesis of depression. These findings suggest that placental extracts may serve as a novel therapeutic strategy for treating stress-related neuroinflammatory disorders such as depression.