Natural products target pyroptosis for ameliorating neuroinflammation: A novel antidepressant strategy

Depression is a common mental disorder characterized by prolonged loss of interest and low mood, accompanied by symptoms such as sleep disturbances and cognitive impairments. In severe cases, there may be a tendency toward suicide. Depression can be caused by a series of highly complex pathological mechanisms; However, its key pathogenic mechanism remains unclear. As a novel programmed cell death (PCD) pathway and inflammatory cell death mode, pyroptosis involves a series of tightly regulated gene expression events. It may play a significant role in the pathogenesis and management of depression by modulating neuroinflammatory processes. In addition, a large number of studies have shown that various pharmacologically active natural products can regulate pyroptosis through multiple targets and pathways, demonstrating significant potential in the treatment of depression. These natural products offer advantages such as low costs and minimal side effects, making them a viable supplement or alternative to traditional antidepressants. In this review, we summarized recent research on natural products that regulate pyroptosis and neuroinflammation to improve depression. The aim of this review was to contribute to a scientific basis for the discovery and development of more natural antidepressants in the future.

To review the antidepressant effects of natural products targeting pyroptosis-mediated neuroinflammation, data were collected from the Web of Science, ScienceDirect databases, and PubMed to classify and summarize the relationship between pyroptosis and neuroinflammation in depression, as well as the pharmacological mechanisms of natural products.

Multiple researches have revealed that pyroptosis-mediated neuroinflammation serves as a pivotal contributory factor in the pathological process of depression. Natural products, such as terpenoids, terpenes, phenylethanol glycosides, and alkaloids, have antidepressant effects by regulating pyroptosis to alleviate neuroinflammation.

We comprehensively reviewed the regulatory effects of natural products in depression-related pyroptosis pathways, providing a uniquely insightful perspective for the research, development, and application of natural antidepressants. However, future research should further explore the modulatory mechanisms of natural products in regulating pyroptosis, which is of great importance for the genration of effective antidepressants.