Seahorse Attenuated DSS-Induced Depression in Mice by Inhibiting Neuroinflammation and Ferroptosis

Seahorse (Hippocampus abdominalis), a small fish, has been extensively utilized in traditional Chinese medicine to enhance and harmonize vital energy throughout the body and brain. This study aimed to elucidate the therapeutic role and underlying mechanism of seahorse in treating depressive symptoms. The therapeutic potential of seahorse was investigated in mice induced by dextran sulfate sodium (DSS) via behavioral tests, histopathological examinations, immunofluorescence staining, and transmission electron microscopy detection. Our findings revealed that seahorse effectively alleviated colitis symptoms by DSS, as shown by reduced inflammatory markers and enhanced expression of claudin-1 in the colonic tissues. More importantly, these gastrointestinal improvements were paralleled by significant attenuation of depressive behaviors, including improved anhedonia and reduced despair-like responses. Furthermore, seahorse exhibited a potent anti-inflammatory effect on brain tissues, evidenced by a decreased number of microglia in the hippocampal CA1 region, reduced expression of pNF-κB and NLRP3, and lowered cytokine levels. Additionally, seahorse promoted neurogenesis in the hippocampal DG region, enhanced brain-derived neurotrophic factor (BDNF) content in the CA1 region, and induced the pNrf2-mediated expression of HO-1, GPX4, and SLC7A11, collectively counteracting DSS-induced hippocampal ferroptosis. Transmission electron microscopy of mitochondria further confirmed that seahorse ameliorated DSS-induced mitochondrial atrophy and cristae deficiency. These results demonstrated that seahorse reversed IBD and comorbid depressive symptoms by regulating inflammation and ferroptosis. Our study highlights the multifaceted efficacy of seahorse in alleviating IBD and comorbid depressive symptoms, potentially offering a novel therapeutic avenue for these conditions.