<i>Alternanthera philoxeroides</i> (Mart.) Griseb Mitigates Age‐Related Depression in Mice Through Regulation of Oxidative Stress and Neurogenic Mechanisms

Depression adversely impacts daily life, with age‐related neurodegeneration being a significant contributing factor. Neurodegenerative alterations, often accelerated by oxidative stress, underlie depressive progression in advanced age. Our previous research has reported that Alternanthera philoxeroides (Mart.) Griseb (AP) exhibits promising antioxidant properties for counteracting age‐related dementia. However, other mechanisms, such as those related to aging‐induced depression, have not been investigated. The present study investigated the therapeutic potential of AP against D‐galactose (D‐gal)‐induced geriatric depression in male mice, with a specific emphasis on its antioxidative properties and neurogenesis‐mediated mechanisms of action. AP extract showed radical scavenging activity by transferring hydrogen atoms and single electrons. Moreover, AP treatment significantly restored the endogenous defensive system and neuronal regeneration, prevented lipid peroxidation in mood‐regulating brain regions, and reduced serum corticosterone levels, alleviating depressive‐like behaviors. Nuclear magnetic resonance (NMR)–based metabolomic pathway analysis revealed that neurotransmitter synthesis, energy production, and protein synthesis were the pathways modulated by AP. Thus, AP extract demonstrated neuroprotective and antidepressive effects in aging‐induced depression, offering a promising source for the treatment of depression in elderly patients. Further research is required to establish its role in treating aging‐related neurodegenerative diseases.