Neuroprotective Effects of 5-Aminolevulinic Acid Combined with Ferrous Iron on Chronic Stress- Induced Depressive-Like Behavior in Mice by Activating the HO-1/Nrf2 Signaling Pathway

Depression, classified as a mental disorder, exerts a profound negative impact on the overall well-being and life satisfaction of individuals affected. The aim of the current study was to investigate the role of 5-Aminolevulinic acid (5-ALA) in treating depression. Previous research has indicated that 5-ALA/ferrous iron (Fe ²⁺ ) possesses anti-oxidative and anti-inflammatory properties. However, the effectiveness of the combination of 5-ALA/Fe ²⁺ in treating depression remains inadequately characterized. In the mice model induced by 6 weeks chronic unpredictable mild stress, 5-ALA/Fe ²⁺ is tested to determine its effect on improving depression-like behavior. In the behavioral tests, 5-ALA/ Fe ²⁺ was found to have anxiolytic effects on mice behavior. The administration with 5-ALA/Fe ²⁺ exhibited significant advantages in terms of decreased oxidative stress and proinflammatory cytokines, and increased levels of neurotransmitters in the hippocampus. Additionally, the group treated with 5-ALA/ Fe ²⁺ exhibited a substantial decrease in the protein expression of IBA-1 and GFAP within the hippocampus of mice. The administration of 5-ALA/Fe ²⁺ promoted the expression of associated proteins within the activated HO-1/Nrf2 pathway, as well as the inhibition of the NLRP3 Inflammasome Activation induced by chronic stress. Consequently, 5-ALA/Fe ²⁺ exhibits promising potential as a therapeutic candidate for the treatment of depression.