{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:30:32Z","timestamp":1786429832188,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":221,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Allergic rhinitis (AR) is a prevalent chronic inflammatory nasal disorder with suboptimal current therapies. Glycyrrhizic acid (GA), a bioactive triterpenoid from\n                      <jats:italic>Glycyrrhiza uralensis<\/jats:italic>\n                      , exerts well\u2010documented antiinflammatory effects, and preliminary evidence indicates its efficacy in alleviating airway inflammation in AR models. However, two critical knowledge gaps remain unaddressed: whether GA directly binds to core proteins of the toll\u2010like receptor 4 (TLR4)\/nuclear factor\u2010kappa B (NF\u2010\u03baB)\/IL\u20101\u03b2 inflammatory pathway, and whether this binding mediates GA\u2019s therapeutic effects in AR have not been systematically verified by integrated computational and in vivo experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An ovalbumin (OVA)\u2010induced AR rat model was established. GA was administered intranasally for seven consecutive days. Behavioral observations, histopathological examination, and serum cytokine detection were performed to evaluate AR\u2010related symptoms and immune imbalance. Molecular docking was employed to assess the binding affinity between GA and four key proteins in the TLR4 pathway (TLR4, myeloid differentiation primary response 88 [MyD88], NF\u2010\u03baB, and IL\u20101\u03b2). About 100\u2009ns molecular dynamics (MD) simulations were further conducted to validate the stability of the GA\u2013protein complexes. Immunohistochemistry and RT\u2010qPCR were used to verify the expression of pathway\u2010related proteins and cytokines in nasal mucosal tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GA significantly reduced sneezing, rhinorrhea, and nasal mucosal pathological damage in AR rats. It restored the T helper 1 (Th1)\/Th2 immune balance by suppressing Th2 cytokines (IL\u20104 and IL\u201013) and enhancing Th1 cytokines (interferon\u2010gamma [IFN\u2010\u03b3] and IL\u20102). Molecular docking results showed that GA bound strongly to all four target proteins, with the highest affinity for IL\u20101\u03b2 (\u22129.3\u2009kcal\/mol) and TLR4 (\u22127.6\u2009kcal\/mol). MD simulations confirmed the stable conformational dynamics of the GA\u2013IL\u20101\u03b2 and GA\u2013TLR4 complexes. In vivo experiments further demonstrated that GA significantly downregulated the expression of TLR4, MyD88, NF\u2010\u03baB, and IL\u20101\u03b2 in nasal mucosa and reduced the levels of downstream proinflammatory cytokines (TNF\u2010\u03b1 and IL\u20106).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GA alleviates AR symptoms by directly binding to core proteins of the TLR4\/NF\u2010\u03baB\/IL\u20101\u03b2 pathway, inhibiting pathway activation, restoring Th1\/Th2 immune balance, and suppressing inflammatory responses. This study provides structural and functional evidence supporting GA as a promising targeted therapeutic candidate for AR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jimr\/6032689","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:08:28Z","timestamp":1786428508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Molecular Docking and Dynamic Simulations Reveal Glycyrrhizic Acid Alleviates Allergic Rhinitis in Rats by Inhibiting the TLR4\/NF\u2010\u03baB\/IL\u20101\u03b2 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