{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T19:44:43Z","timestamp":1776973483945,"version":"3.51.4"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860224"],"award-info":[{"award-number":["81860224"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Licorice (\n                      <jats:italic>Glycyrrhiza<\/jats:italic>\n                      spp.), a traditional Chinese herb, contains glycyrrhetinic acid derivatives with neuroprotective properties but limited bioavailability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      YCY\u201020 is a novel derivative synthesized by structural modification of 18\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010glycyrrhetinic acid. The aim of this study is to explore its therapeutic effect and potential molecular mechanism on cerebral ischemia\u2013reperfusion injury (CIRI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Pharmacokinetic profiling was performed to compare plasma exposure and brain distribution of YCY\u201020 and its parent compound 18\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010GA. Neuroprotection was assessed using middle cerebral artery occlusion\/reperfusion (MCAO\/R) rats and oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R)\u2010induced HT22 cells. Evaluations included infarct volume (TTC staining), apoptosis (TUNEL, flow cytometry), and protein dynamics (Western blot). Network pharmacology identified potential targets, and in\u00a0vivo experiments are conducted to validate the relevant molecular pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      YCY\u201020 exhibited improved pharmacokinetic properties, with higher and more stable plasma concentrations and detectable brain levels after oral administration, compared with 18\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010GA. YCY\u201020 administration significantly attenuated body weight loss, cerebral infarct volume, and neuronal apoptosis in MCAO\/R rats. Mechanistically, YCY\u201020 suppressed the MCAO\/R\u2010induced upregulation of pro\u2010apoptotic proteins (Bax, caspase\u20103, cleaved caspase\u20103) while restoring anti\u2010apoptotic Bcl\u20102 expression. In\u00a0vitro OGD\/R models corroborated these anti\u2010apoptotic effects. Network analysis identified AGE\u2010RAGE\/MAPK signaling as the predominant pathway modulated by YCY\u201020, with subsequent in\u00a0vivo validation demonstrating its capacity to downregulate key mediators in this pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>YCY\u201020 confers protection against CIRI, at least partially through apoptosis inhibition mediated by AGE\u2010RAGE\/MAPK signaling pathway modulation. This study provides preclinical evidence for developing licorice\u2010derived agents in stroke management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70792","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T10:37:44Z","timestamp":1771324664000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Glycyrrhizinic Acid Derivative\n                    <scp>YCY<\/scp>\n                    \u201020 Inhibits Cerebral Ischemia\/Reperfusion Induced Apoptosis via the\n                    <scp>AGE<\/scp>\n                    \u2010\n                    <scp>RAGE<\/scp>\n                    \/\n                    <scp>MAPK<\/scp>\n                    Pathway"],"prefix":"10.1002","volume":"32","author":[{"given":"Jia","family":"Luo","sequence":"first","affiliation":[{"name":"Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education Shihezi University 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