{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T13:02:38Z","timestamp":1792242158345,"version":"4.4.0"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82505059"],"award-info":[{"award-number":["82505059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82505059"],"award-info":[{"award-number":["82505059"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Science and Technology Development Fund (FDCT) of Macao SAR","award":["FDCT 0008\/2023\/AMR"],"award-info":[{"award-number":["FDCT 0008\/2023\/AMR"]}]},{"award":["FDCT 0008\/2023\/AMR"],"award-info":[{"award-number":["FDCT 0008\/2023\/AMR"]}],"id":[{"id":"https:\/\/ror.org\/05vna4324","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004377","name":"The Hong Kong Polytechnic University","doi-asserted-by":"publisher","award":["A0051173"],"award-info":[{"award-number":["A0051173"]}],"id":[{"id":"10.13039\/501100004377","id-type":"DOI","asserted-by":"publisher"}]},{"award":["A0051173"],"award-info":[{"award-number":["A0051173"]}],"id":[{"id":"https:\/\/ror.org\/0030zas98","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neuroinflammation, mediated by microglia and astrocytes, is an abnormal immune reaction in central nervous system (CNS) disorders. Stimulation of TRPV1 has been found to enhance microglial activation, resulting in a pro-inflammatory response. Natural anthraquinones such as physcion and rhein are commonly found in rhubarb, a medicinal plant recognized for its dual role in culinary and therapeutic applications. The therapeutic potential and mechanisms of these anthraquinones remain largely unexplored. This research aims to examine how anthraquinones protect against neuroinflammation and delineate the underlying mechanisms in lipopolysaccharide (LPS)-mediated cellular and zebrafish models. Among the representative anthraquinone analogs, physcion and rhein showed potent functional inhibitory activity against the TRPV1 channel. The production of nitric oxide (NO) and secretion of pro-inflammatory factors triggered by LPS were significantly reduced in BV-2 cells through regulation of iNOS, IL-6, IL-1\u03b2, and TNF-\u03b1 mRNA expression. Moreover, physcion and rhein inhibited calcium influx and exerted anti-neuroinflammatory effects, which were closely associated with the suppression of Ca2+\/CAMKK2\/AKT and the PI3K\/AKT-mediated NF-\u03baB activation pathways. Furthermore, physcion and rhein reduced LPS-driven neutrophil recruitment to the brain and ameliorated locomotor deficits in zebrafish larvae, with the restoration of IL-1\u03b2, IL-6, and TNF-\u03b1 transcript levels to baseline. In conclusion, natural-derived anthraquinones from rhubarb, physcion and rhein, acted as functional inhibitors of TRPV1-mediated calcium dynamics and significantly reduced LPS-mediated neuroinflammation in microglial cells and zebrafish larvae, suggesting promise as therapeutics for neurological disorders.<\/jats:p>","DOI":"10.3390\/molecules31122049","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:14:58Z","timestamp":1781180098000},"page":"2049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Rhubarb Anthraquinones Physcion and Rhein as Functional Inhibitors of TRPV1 Against Lipopolysaccharide-Induced Neuroinflammation"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6567-8605","authenticated-orcid":false,"given":"Shuli","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mechanism and 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