Hemoglobin-derived peptides and mood regulation

Abstract Evidence accumulated over the past decades has revealed that red blood cells and hemoglobin (Hb) in the blood play important roles in modulating moods and emotions. The number of red blood cells affects the mood. Hb is the principal content in the red blood cells besides water. Denatured Hb is hydrolyzed to produce bioactive peptides. RVD-hemopressin α (RVD-Hpα), which is a fragment of α-chain (95-103) in Hb, functions as a negative allosteric modulator of cannabinoid receptor 1 and a positive allosteric modulator of cannabinoid receptor 2. Hemorphins, which are fragments of β-chain in Hb, exert their effects on opioid receptors. Two hemorphins, namely, LVV-hemorphin-6 and LVV-hemorphin-7, could induce anxiolytic-like effects. The use of Hb-derived bioactive peptides for the treatment of mood disorders is desirable due to cannabinoid–opioid cross modulation and the critical roles of the two systems in physiological processes, such as memory, mood and emotion.