{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T07:38:28Z","timestamp":1773041908482,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Leonurus japonicus<\/jats:italic>\n                      Houtt. has been traditionally used as a gynecological remedy and is now recognized for its anti-inflammatory and immunomodulatory properties. But its potential therapeutic role in allergic asthma is unclear. This study aimed to investigate the anti-asthmatic effects of the total alkaloids of Leonurus (TAL) and their regulation of mast cell activation through the hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      An ovalbumin (OVA)-induced asthma mouse model was used to detect TAL\u2019s effects on airway hyperresponsiveness, lung inflammation, and Th2 cytokines. For\n                      <jats:italic>in vitro<\/jats:italic>\n                      studies, RBL-2H3 cells were employed as a mast cell model. Transcriptomics and cross-species analysis integrated rat signatures with human asthma datasets using KEGG enrichment to identify conserved HIF-1\u03b1\u2013related pathways. HIF-1\u03b1 expression and localization were analyzed by Western blotting and immunofluorescence. Mast cell degranulation was evaluated\n                      <jats:italic>via<\/jats:italic>\n                      \u03b2-hexosaminidase (\u03b2-hex) assay and Th2 cytokines detection. Constructed a HIF-1\u03b1 stable overexpression cell or applied pharmacological inhibition (YC-1) to verify the key role of HIF-1\u237a on TAL\u2019s efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TAL significantly alleviated allergic symptoms, reduced airway hyperresponsiveness, and decreased lung mast cell infiltration. Transcriptomic analysis revealed that hypoxia-related pathways, particularly HIF-1\u03b1, were downregulated following TAL intervention. TAL suppressed HIF-1\u03b1 protein expression, reduced mast cell degranulation, and Th2 cytokines both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Mechanistically, hypoxia induced HIF-1\u03b1 upregulation, mast cell activation, and cytokine release, whereas TAL inhibited these responses. This effect was weakened by HIF-1\u03b1 overexpression but potentiated by YC-1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TAL alleviates allergic asthma by suppressing HIF-1\u03b1-mediated mast cell activation and associated inflammation responses, supporting its potential application in inflammatory airway diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1783196","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:47:56Z","timestamp":1773038876000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Total alkaloids of Leonurus alleviate allergic asthma and inflammation responses by inhibiting hypoxia-induced factor-1\u237a-mediated mast cell activation"],"prefix":"10.3389","volume":"17","author":[{"given":"Yannan","family":"Zheng","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]},{"name":"Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyue","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]},{"name":"Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhichao","family":"Xi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]},{"name":"Engineering Research Center of Shanghai Colleges for 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