Natural products for the treatment of depression: Insights into signal pathways influencing the hypothalamic-pituitary-adrenal axis

Depression, a prevalent psychiatric malady, afflicts a substantial global demographic, engendering considerable disease burden due to its elevated morbidity and mortality rates. Contemporary therapeutic approaches for depression encompass the administration of serotonin reuptake inhibitors, monoamine oxidase inhibitors, and tricyclic antidepressants, albeit these pharmaceuticals potentially induce adverse neurological and gastrointestinal effects. Traditional Chinese Medicine (TCM) natural products proffer the benefits of multi-target, multi-level, and multi-channel depression treatment modalities. In this investigation, we conducted a comprehensive literature review of the past 5 years in PubMed and other databases utilizing the search terms Depression, Natural medicines, Traditional Chinese Medicine, and hypothalamic-pituitary-adrenal axis. We delineated the 5 most recent and pertinent signaling pathways associated with depression and hypothalamic-pituitary-adrenal (HPA) axis dysregulation: nuclear factor kappa light-chain-enhancer of activated B cell, brain-derived neurotrophic factor, mitogen-activated protein kinase, cyclic AMP/protein kinase A, and phosphoinositide 3-kinase/protein kinase B. Additionally, we deliberated the antidepressant mechanisms of natural medicines comprising alkaloids, flavonoids, polyphenols, saponins, and quinones via diverse pathways. This research endeavor endeavored to encapsulate and synthesize the progression of TCMs in modulating HPA axis-associated signaling pathways to mitigate depression, thereby furnishing robust evidence for ensuing research in this domain.

Automated summary

Depression is a prevalent psychiatric disorder with high morbidity and mortality rates. Traditional Chinese Medicine (TCM) natural products offer multi-target, multi-level, and multi-channel treatment modalities for depression. This study reviewed recent literature on depression and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and discussed the antidepressant mechanisms of natural medicines through various pathways.