{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:45:22Z","timestamp":1775108722093,"version":"3.50.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1814913","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T04:20:52Z","timestamp":1775103652000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The therapeutic potential of compounds from natural products for alleviating depression by targeting P2X7 receptor-mediated proinflammatory signaling pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Xin-Yang","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology and Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province, Henan 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