Accessible, and non-pharmacological strategy, has been widely shown to alleviate depressive symptoms. Nevertheless, most previous studies have interpreted the antidepressant effects of exercise from isolated perspectives, such as inflammation, neurotransmitter regulation, or neuroplasticity, without offering a systematic integration based on the overall mechanism of the heart-brain axis. Accordingly, this review aims to clarify the potential mechanisms through which exercise improves depression from the perspective of the heart-brain axis and to provide a new analytical framework for understanding the coordinated regulation of emotional state and cardiocerebral function by exercise.

Based on a systematic review of relevant domestic and international literature, this paper integrates research advances from psychiatry, cardiovascular medicine, neuroscience, exercise science, and traditional Chinese medicine to summarize and discuss the neurobiological basis of the heart-brain axis and its role in exercise-induced improvement of depression. First, the theoretical connotation of the heart-brain axis is interpreted from the perspective of the autonomic nervous system, the central autonomic network, and bidirectional heart-brain regulation in modern medicine, in combination with the holistic concept in traditional Chinese medicine that the heart and brain co-governing "Shenming" (mind and spirit). Second, the pathways through which exercise affects depression are analyzed from the dimensions of neural regulation, biochemical homeostasis, central remodeling, and heart-brain comorbidity. Finally, guided by the FITT-VP principle, key elements of exercise prescription, including frequency, intensity, time, type, volume, and progression, are summarized.

Current evidence indicates that the antidepressant effects of exercise largely overlap with mechanisms of the heart-brain axis. Depression is characterized by reduced heart rate variability, impaired vagal tone, elevated inflammation, HPA axis hyperactivity, decreased cerebral perfusion, and compromised neuroplasticity. Exercise may counter these alterations by enhancing baroreflex sensitivity, restoring autonomic balance, and strengthening vagal afferent signaling to emotion-related brain regions. It also reduces inflammatory load and stress hormones, optimizing the neuroendocrine-immune environment. Centrally, exercise improves cardiovascular function and cerebral blood flow, increases brain-derived neurotrophic factor expression, and promotes functional remodeling in key regions such as the hippocampus and prefrontal cortex. Given the high comorbidity between depression and cardiovascular disease, exercise may provide integrated protection by disrupting the vicious cycle linking emotional dysregulation, autonomic imbalance, and cardiac dysfunction.

Overall, the heart-brain axis may represent a key integrative framework for elucidating the antidepressant effects of exercise. This perspective transcends reductionist models that isolate single pathways, emphasizing instead the systemic psychosomatic benefits arising from coordinated regulation of cardiac and neural processes. It offers a refined theoretical basis for exercise-based interventions and aligns with the holistic concept of "simultaneous regulation of the heart and brain." However, current evidence remains largely indirect, with a paucity of targeted empirical studies. Future research should therefore further verify the relevant mechanistic pathways and identify sensitive biomarkers as well as optimal exercise doses for different populations, so as to enhance both theoretical explanatory power and clinical translational value.