{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:32:41Z","timestamp":1785450761632,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition\u2010enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes\u2010associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes\u2010associated memory impairment in streptozotocin\u2010induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide\u2010binding domain and leucine\u2010rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end\u2010products and its receptor (AGEs\/RAGE) axis and suppressed up\u2010regulation of thrombin receptor protease\u2010activated receptor 1 (PAR\u20101) in cerebral cortex. On the other hand, Sar mitigated high glucose\u2010induced neuronal damages, NLRP1 inflammasome activation, and PAR\u20101 up\u2010regulation in high glucose\u2010cultured SH\u2010SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR\u20101 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF\u2010\u03baB mediated the effect of PAR\u20101 up\u2010regulation in high glucose condition by using PAR\u20101 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF\u2010\u03baB regulated by cerebral PAR\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Sarsasapogenin ameliorated memory impairment caused by diabetes in rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sarsasapogenin mitigated neuronal damages and neuroinflammation by down\u2010regulating cerebral PAR\u20101.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The NLRP1 inflammasome and NF\u2010\u03baB signaling mediated the pro\u2010inflammatory effects of PAR\u20101.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic 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