{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T06:00:04Z","timestamp":1783490404344,"version":"3.55.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"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:sec><jats:title>Background<\/jats:title><jats:p>Linarine is a natural chemical component widely found in Buddleja officinalis Maxim., Chrysanthemum indicum L., Mentha canadensis L., and other medicinal plants. Modern pharmacological studies have shown that linarine with good anti-inflammatory and antioxidant activities can inhibit the proliferation and induce apoptosis of many kinds of tumor cells. Moreover, linarine showed protective effect on the liver, kidneys, and other organs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Inflammation model of human corneal epithelial cell (HCEC) was constructed using NaCl induction, and cytotoxicity was detected by the CCK8 assay. The levels of inflammatory factors tumor necrosis factor-\u03b1 (TNF-\u03b1) and interleukin 1\u03b2 (IL-1\u03b2) were measured using Enzyme-linked immunoassay (ELISA). Chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops in a desiccator established a mouse model of dry eye disease (DED). The following parameters were recorded: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. The levels of inflammatory factors mitogen activated protein kinase (MAPK), nuclear factor kappa-B (NF-kB), c-Jun N-terminal kinase (JNK), IL-1\u03b2, Interleukin 18(IL-18), A2A, A3, P2X4, P2X7, P2Y1 were measured by using immunofluorescence (IF) staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Linarine can inhibit the secreation of TNF-\u03b1, and IL-1\u03b2 in HCECs. Linarine prolonged tear film rupture time, promoted tear secretion, repaired corneal damage, and reduced the levels of inflammatory factors of MAPK, NF-kB, JNK, IL-1\u03b2, IL-18, and modulated the levels of the purinergic receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Linarine is effective in treating dry eye in mice by inhibiting purinergic receptors-mediated inflammatory response.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1463767","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T04:31:22Z","timestamp":1727670682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Linarine inhibits inflammatory responses in dry eye disease mice by modulating purinergic 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