Depression, stress, and tryptophan metabolism through the kynurenine pathway: treatment strategies from the perspective of Chinese herbal medicine

The pathogenesis of depression is complex, involving abnormalities in tryptophan (TRP) metabolism through the kynurenine pathway (KP). Moreover, depression is closely related to the hypothalamic-pituitary-adrenal (HPA) axis, the gut-brain axis, neuroinflammation, and stress. These factors collectively influence the multidimensional pathological mechanisms of depression. TRP, a fundamental amino acid, serves as a precursor for neuroactive metabolites vital to physiological functions. Central to TRP metabolism is the KP, and the imbalance between neurotoxic and neuroprotective metabolites is closely related to the onset and progression of depression. Therefore, maintaining the balance of KP metabolites is important. In this review, we have investigated the role of the KP in depression and explored the complexity of KP dysregulation and its therapeutic importance. Here, we highlight how a deeper understanding of the KP and its regulation can pave the way for new treatment strategies. Specifically, we have summarized the latest advances in elucidating the key mechanisms of rate-limiting enzyme inhibitors, providing insights into their potential therapeutic efficacy. In addition, we have explored the emerging field of Chinese herbal medicine, discussing its potential to regulate KP metabolites and alleviate depressive symptoms, thereby expanding the treatment options for depression. Our findings emphasize the multifaceted nature of depression and the necessity of interdisciplinary research to fully utilize KP regulation and Chinese herbal medicine as strategies to advance the treatment of depression.