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Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The NLRP3 inflammasome is a multiprotein complex of the innate immune system that mediates the maturation and secretion of interleukin-1\u03b2 (IL-1\u03b2) and plays a pivotal role in the pathogenesis of chronic inflammatory diseases, including asthma, metabolic disorders, and autoimmune diseases. However, natural product\u2013derived metabolites that directly modulate NLRP3 activation remain limited. This study aimed to investigate the inhibitory effects of\n                      <jats:italic>Thymelaea hirsuta<\/jats:italic>\n                      extract (TMH) on NLRP3 inflammasome activation and to elucidate its underlying mechanism of action.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TMH was prepared by methanol extraction and chemically profiled using UPLC-QTOF\/MS analysis. Human monocytic THP-1 cells and murine macrophage J774A.1 cells were used to evaluate inflammasome activation. Following lipopolysaccharide (LPS) priming, cells were stimulated with ATP or nigericin to induce NLRP3 inflammasome activation. IL-1\u03b2 secretion was quantified by ELISA, and the expression of NLRP3 inflammasome-related proteins was evaluated by Western blot analysis. Cell viability was assessed using the EZ-CYTOX assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TMH exhibited no cytotoxicity at concentrations up to 100\u00a0\u03bcg\/mL. TMH treatment (10, 50, and 100\u00a0\u03bcg\/mL) significantly reduced LPS\/ATP- or LPS\/nigericin-induced IL-1\u03b2 secretion. However, even at the highest concentration tested (100\u00a0\u03bcg\/mL), TMH did not significantly affect pro-IL-1\u03b2 expression or NF-\u03baB signaling, indicating that the priming step was not altered. Instead, TMH suppressed NLRP3 inflammasome activation during the activation phase. In addition, TMH treatment at 1\u00a0\u03bcg\/mL was associated with reduced NLRP3 ATPase activity, suggesting a potential effect on inflammasome assembly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TMH attenuated NLRP3 inflammasome activation without affecting the priming step. These findings suggest that TMH may act as a natural product\u2013derived modulator of NLRP3-mediated inflammatory responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1781860","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:44:39Z","timestamp":1776231879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Thymelaea hirsuta (L.) Endl. extract attenuates NLRP3 inflammasome activation via modulation of ATPase activity"],"prefix":"10.3389","volume":"17","author":[{"given":"Seongjong","family":"Lee","sequence":"first","affiliation":[{"name":"BK21 R&E Initiative for Advanced Precision Medicine, Ajou University School of Medicine","place":["Suwon, Republic of Korea"]},{"name":"Department of Microbiology, Ajou University School of Medicine","place":["Suwon, Republic of Korea"]},{"name":"Department of Biomedical Sciences, Graduate School of Ajou University","place":["Suwon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyeon","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Technology, Kyung Hee University","place":["Seoul, Republic of Korea"]},{"name":"School of Medicine, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangyeol","family":"Lee","sequence":"additional","affiliation":[{"name":"Natural Product Research Center and Natural Product Central Bank, KRIBB","place":["Cheongju-si, Chungcheongbuk-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Khorchani","sequence":"additional","affiliation":[{"name":"Laboratory of Management and Valorization of Forest Resources, The National Research Institute of Rural Engineering, Water, and Forestry. 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