{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:01:48Z","timestamp":1793826108196,"version":"4.6.1"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"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:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Ischemic stroke seriously threatens human health because of high rates of morbidity, mortality and disability. This study compared the effects of nicotinamide adenine dinucleotide (NAD\n                    <jats:sup>+<\/jats:sup>\n                    ) and butylphthalide (NBP) on\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    ischemic stroke models.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Transient middle cerebral artery occlusion\/reperfusion (t-MCAO\/R) model was established in mice, and the cultured primary cortical neurons were subjected to oxygen-glucose deprivation\/reoxygenation (OGD\/R). Cerebral infarct volume, neurobehavioral indices, antioxidant activity, ATP level and lactic acid content were determined. The neuroprotective effects of NAD\n                    <jats:sup>+<\/jats:sup>\n                    or NBP were compared using sirtuin inhibitor niacinamide (NAM).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Intraperitoneal injection of NBP within 4\u00a0h or intravenous injection of NAD\n                    <jats:sup>+<\/jats:sup>\n                    within 1\u00a0h after t-MCAO\/R significantly reduced the volume of infarcts, cerebral edema, and neurological deficits. Administration of NAD\n                    <jats:sup>+<\/jats:sup>\n                    and NBP immediately after t-MCAO\/R in mice showed similar neuroprotection against acute and long-term ischemic injury. Both NAD\n                    <jats:sup>+<\/jats:sup>\n                    and NBP significantly inhibited the accumulation of MDA and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and reduced oxidative stress. NAD\n                    <jats:sup>+<\/jats:sup>\n                    was superior to NBP in inhibiting lipid oxidation and DNA damage. Furthermore, although both NAD\n                    <jats:sup>+<\/jats:sup>\n                    and NBP improved the morphology of mitochondrial damage induced by ischemia\/reperfusion, NAD\n                    <jats:sup>+<\/jats:sup>\n                    more effectively reversed the decrease of ATP and increase of lactic acid after ischemia\/reperfusion compared with NBP. NAD\n                    <jats:sup>+<\/jats:sup>\n                    but not NBP treatment significantly upregulated SIRT3 in the brain, but the sirtuin inhibitor NAM could abolish the protective effect of NAD\n                    <jats:sup>+<\/jats:sup>\n                    and NBP by inhibiting SIRT1 or SIRT3.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    These results confirmed the protective effects of NAD\n                    <jats:sup>+<\/jats:sup>\n                    and NBP on cerebral ischemic injury. NBP and NAD\n                    <jats:sup>+<\/jats:sup>\n                    showed similar antioxidant effects, while NAD\n                    <jats:sup>+<\/jats:sup>\n                    had better ability in restoring energy metabolism, possibly through upregulating the activity of SIRT1 and SIRT3. The protection provided by NBP against cerebral ischemia\/reperfusion may be achieved through SIRT1.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2023.1096533","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T01:08:23Z","timestamp":1679965703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Neuroprotection of NAD+ and NBP against ischemia\/reperfusion brain injury is associated with restoration of sirtuin-regulated metabolic homeostasis"],"prefix":"10.3389","volume":"14","author":[{"given":"Xin-Xin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Hui","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Qi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Hong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14447","DOI":"10.1073\/pnas.0803790105","article-title":"'A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis","volume":"105","author":"Ahn","year":"2008","journal-title":"Proc. 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