@article {Chen1265, author = {Feichi Chen and Weiqian Lin}, title = {Anti-apoptosis effects of codonolactone on cerebral ischemia-reperfusion injury}, volume = {70}, number = {5}, pages = {1265--1272}, year = {2022}, doi = {10.1136/jim-2021-002113}, publisher = {BMJ Publishing Group Limited}, abstract = {Codonolactone is the main biologically active ingredient in Atractylodes lancea. Studies have shown various functions of codonolactone, while its protective effect against neurotoxicity caused by ischemic stroke is unclear. This study investigated the roles of codonolactone in inflammation, oxidative stress and apoptosis after cerebral ischemia-reperfusion (I/R) injury. Rats with codonolactone treatment, I/R treatment and the sham operation group were used in this study. After reperfusion for 24 hours, nerve damage was detected by nerve staining, and the neurological deficits of the rats were analyzed. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in rat brain tissues were also determined. Western blot analysis was performed to determine the expression levels of Akt/Nrf2 pathway-associated proteins. Compared with the I/R group, the cerebral blood flow, infarct volume, brain water content, coronary blood flow and neurological deficits in the codonolactone treatment group, especially with the 80 mg/kg dosage, were significantly reduced. Codonolactone could significantly reduce the expression levels of caspase-3 and Bax, and significantly increase the expression levels of Bcl-2 after I/R. In addition, codonolactone could significantly reduce MDA content and the expression levels of TNF-α and IL-1β in ischemic brain tissues. It also significantly increased SOD activity, the expression levels of heme oxygenase-1 (HO-1) and the phosphorylation of Akt and Nrf2. Codonolactone ameliorated the cerebral I/R injury by improving anti-oxidant, anti-inflammatory activities and reducing apoptosis. Besides, the Akt/Nrf2 pathway was involved in the pharmacological action of the codonolactone.Data are available on reasonable request. The datasets used and/or analyzed during the current study is available from the corresponding author on reasonable request.}, issn = {1081-5589}, URL = {http://hw-f5-jim.highwire.org/content/70/5/1265}, eprint = {http://hw-f5-jim.highwire.org/content/70/5/1265.full.pdf}, journal = {Journal of Investigative Medicine} }