{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:05:22Z","timestamp":1774940722243,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"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>Objective<\/jats:title>\n                    <jats:p>This study investigated the protective effect of Salidroside (SAL) against cerebral ischemia-reperfusion (I\/R) injury and its role in regulating nicotinamide phosphoribosyltransferase (NAMPT)-mediated neuroinflammation and damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      , a middle cerebral artery occlusion\/reperfusion (MCAO\/R) model was established in male SD rats. Animals were divided into sham-operated (Sham), I\/R (MCAO-NS), MCAO+eNAMPT, and MCAO+eNAMPT+SAL groups. Recombinant NAMPT (5 \u03bcg\/rat) and\/or SAL (10 \u03bcg\/rat) were administered intracerebroventricularly. Neurological deficit scores (mNSS), infarct volume (TTC), brain levels of IL-1\u03b2\/TNF-\u03b1 (ELISA), total NAMPT expression (WB\/ELISA), and NAD+ content were assessed.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , primary microglia were subjected to oxygen-glucose deprivation\/reoxygenation (OGD\/R) and divided into control (Ctrl), OGD-NS, OGD+eNAMPT (20\u00a0ng\/mL), and OGD+eNAMPT+SAL (6\u00a0\u03bcg\/mL) groups. Cytotoxicity (LDH), viability (MTT), and IL-1\u03b2\/TNF-\u03b1 secretion (ELISA) were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to Sham, the I\/R group showed worsened neurological deficits, larger infarct volumes, elevated total NAMPT, TNF-\u03b1, and IL-1\u03b2 levels (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001), and reduced NAD+ (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). Exogenous eNAMPT further exacerbated these injuries and inflammation (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). SAL treatment significantly reversed eNAMPT-aggravated neurological deficits and infarction (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001), downregulated total NAMPT, TNF-\u03b1, and IL-1\u03b2, and increased NAD+ levels (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001).\n                      <jats:italic>In vitro<\/jats:italic>\n                      , eNAMPT stimulation increased OGD\/R-induced TNF-\u03b1 and IL-1\u03b2 secretion from microglia (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001), which SAL effectively inhibited (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides experimental evidence that the neuroprotective effects of SAL against cerebral I\/R injury are associated with downregulation of pathologically elevated NAMPT expression (likely reflecting a reduction in pro-inflammatory eNAMPT), restoration of cerebral NAD+ homeostasis (potentially preserving iNAMPT function), and suppression of microglia-mediated neuroinflammation, suggesting that eNAMPT may serve as a potential effector molecule of SAL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1800667","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:33:39Z","timestamp":1774935219000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective effects of salidroside against cerebral ischemia-reperfusion injury involve downregulation of total NAMPT and suppression of microglial inflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Meng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junchao","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Tongde Hospital of Zhejiang Province","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilin","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Liangzhu Community Health Service Center","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"107848","DOI":"10.1016\/j.pharmthera.2021.107848","article-title":"Targeting autophagy in ischemic stroke: from molecular mechanisms to clinical therapeutics","volume":"225","author":"Ajoolabady","year":"2021","journal-title":"Pharmacol. 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