The therapeutic potential of traditional Chinese medicine in depression: Targeting adult hippocampal neurogenesis

Background: Depression is a common mental disorder characterized by persistent sadness and lack of interest or pleasure in previously rewarding or enjoyable activities. Understandably, the causes of depression are complex. Nevertheless, the understanding of depression pathophysiology has progressed considerably and numerous studies indicate that hippocampal neurogenesis plays a pivotal role. However, no drugs specifically targeting hippocampal neurogenesis yet exist. Meanwhile, the effects of traditional Chinese medicine (TCM) on hippocampal neurogenesis have received increasing attention in the field of antidepressant treatment because of its multi-ingredient, multi-target, and holistic view. However, the effects and mechanisms of TCM on hippocampal neurogenesis in clinical trials and pharmaceutical studies remain to be comprehensively delineated. Purpose: To summarize the importance of hippocampal neurogenesis in depression and illustrate the targets and mechanisms of hippocampal neurogenesis regulation that underlie the antidepressant effects of TCM. Method: A systematic review of clinical trials and studies ending by January 2022 was performed across eight electronic databases (Web of Science, PubMed, SciFinder, Research Gate, ScienceDirect, Google Scholar, Scopus and China Knowledge Infrastructure) according to the PRISMA criteria, using the search terms 'traditional Chinese medicine' "AND" 'depression' "OR" 'hippocampal neurogenesis' "OR" 'multi-ingredient' "OR" 'multi target'. Results: Numerous studies show that hippocampal neurogenesis is attenuated in depression, and that antidepressants act by enhancing hippocampal neurogenesis. Moreover, compound Chinese medicine (CCM), Chinese meteria medica (CMM), and major bioactive components (MBCs) can promote hippocampal neurogenesis exerting antidepressant effects through modulation of neurotransmitters and receptors, neurotrophins, the hypothalamic-pituitary-adrenal axis, inflammatory factors, autophagy, and gut microbiota. Conclusion: We have comprehensively summarized the effect and mechanism of TCM on hippocampal neurogenesis in depression providing a unique perspective on the use of TCM in the antidepressant field. TCM has the characteristics and advantages of multiple targets and high efficacy, showing great potential in the field of depression treatment.