{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:37:35Z","timestamp":1792291055049,"version":"4.4.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To verify that Triptolide alleviates hyperosmotic stress-induced damage to human corneal epithelial cells (HCECs) by suppressing pyroptosis via the Toll-like receptor 4\/nuclear factor-\u03baB\/NOD-like receptor family, pyrin domain-containing 3 (TLR4\/NF-\u03baB\/NLRP3) axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HCECs were divided into six groups: control (CG), hyperosmotic model (MG, 500\u202fmOsm for 12\u202fh), hyperosmotic model with LPS (MG\u202f+\u202fLPS), triptolide intervention (THSG, 30\u202fnM in 500\u202fmOsm medium), triptolide with LPS (THSG\u202f+\u202fLPS), and triptolide-only (TOG, 30\u202fnM in standard medium). Cell viability was detected using Cell Counting Kit-8 (CCK-8). The pyroptosis rate was measured by flow cytometry, and lactate dehydrogenase (LDH) release was quantified to assess cytotoxicity. Inflammatory cytokines interleukin-1\u03b2 (IL-1\u03b2) and interleukin-8 (IL-8) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression levels of NLRP3 and NF-\u03baB were analyzed by quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. NF-\u03baB p65 nuclear translocation was detected by immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to the CG (100.00\u202f\u00b1\u202f0.00)%, MG significantly reduced HCECs proliferation to (54.47\u202f\u00b1\u202f3.10)% and increased the pyroptosis rate to (40.28\u202f\u00b1\u202f3.74)%. LPS further exacerbated these effects in the MG\u202f+\u202fLPS. The levels of inflammatory cytokines IL-1\u03b2 and IL-8 were markedly elevated under hyperosmotic conditions, and further increased with LPS stimulation. THSG significantly ameliorated hyperosmotic-induced injury: cell proliferation increased to (86.47\u202f\u00b1\u202f5.51)%, the pyroptosis rate decreased to (17.01\u202f\u00b1\u202f2.33)%, and the release of IL-1\u03b2 and IL-8 was substantially reduced. Triptolide also downregulated mRNA and protein expression of NLRP3 and NF-\u03baB, and inhibited NF-\u03baB p65 nuclear translocation. In the THSG\u202f+\u202fLPS group, triptolide partially reversed the LPS-enhanced inflammatory and pyroptotic responses, though its protective effect was attenuated compared to THSG without LPS. Notably, TOG showed no adverse effects on normal HCECs, with proliferation, pyroptosis rate, and inflammatory cytokine levels comparable to those of the CG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Triptolide alleviates hyperosmotic stress-induced pyroptosis and inflammatory injury in HCECs, likely through inhibiting the TLR4\/NF-\u03baB\/NLRP3 pathway. This study suggests the potential of triptolide in treating hyperosmolarity-related ocular surface diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1753857","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:24:42Z","timestamp":1772169882000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Triptolide alleviates hyperosmotic stress-induced human corneal epithelial cell damage by inhibiting NLRP3 inflammasome-mediated pyroptosis via the TLR4\/NF-\u03baB pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Ran","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Second Hospital Affiliated to Anhui Medical University","place":["Hefei, China"]},{"name":"Department of Ophthalmology, Anhui No.2 Provincial People\u2019s Hospital","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Hospital Affiliated to Anhui Medical University","place":["Hefei, China"]},{"name":"Department of Ophthalmology, Anhui No.2 Provincial People\u2019s Hospital","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Hospital Affiliated to Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4302","DOI":"10.1167\/iovs.04-0299","article-title":"Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial 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