The therapeutic potential of compounds from natural products for alleviating depression by targeting P2X7 receptor-mediated proinflammatory signaling pathways

Depression is a prevalent neuropsychiatric disorder with high incidence and causing severe disability, representing a clinically unmet challenge and thus demanding more effective therapeutics. Neuroinflammation in the central nervous system (CNS) is a pathological feature of depression and, with increasing recognition, it is also a critical depression-driving mechanism. In the CNS, the P2X7 receptor for extracellular ATP is expressed in microglia and astrocytes, and acts as a key mediator of neuroinflammation. Besides medicinal chemistry efforts in developing novel CNS-penetrable P2X7 antagonists, there is an increasing interest in exploring natural products as medications for CNS conditions including depression. In this mini-review, we discuss the recent progress in examining the therapeutic potential and mechanisms of compounds from natural products, using rodent models of depression, and revealing P2X7-mediated proinflammatory signaling pathways as an important target for their antidepressant actions.