一氧化氮合酶
丙二醛
药理学
每1
医学
超氧化物歧化酶
大脑中动脉
肿瘤坏死因子α
谷胱甘肽
缺血
麻醉
内分泌学
化学
内科学
一氧化氮
时钟
昼夜节律
氧化应激
生物化学
生物钟
酶
作者
Sanli Zhang,Yu Yan,Mingyue Sheng,Xun Chen,Qi Wu,Junping Kou,Gangling Chen
出处
期刊:Phytomedicine
[Elsevier]
日期:2023-11-01
卷期号:120: 155028-155028
被引量:1
标识
DOI:10.1016/j.phymed.2023.155028
摘要
Ruscogenin (Rus), a steroidal sapogenin extracted from Ophiopogon japonicus (L. f.) Ker-Gawl., has the effect of alleviating cerebral ischemia-reperfusion injury (IRI), acute lung injury. At present, the chronopharmacological effects of Rus are still unknown. This study explored the alleviating effect and mechanism of Rus timing administration on mice cerebral IRI. The animals in different groups were administrated Rus (10 mg/kg) by gavage at four time points (23:00–01:00, 05:00–07:00, 11:00–13:00, 17:00–19:00) respectively for 3 days. On the 4th day, middle cerebral artery occlusion (MCAO) surgery was operated during 5:00–7:00. Behavioral tests were executed and the brain was collected for infarct volume, qPCR and immunoblot detection. The levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin-1beta (IL-1β) and inducible nitric oxide synthase (iNOS) were detected by qPCR. Glutathione (GSH), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in serum and cerebral cortex were detected. The clock genes were tested by western blot. Based on these results, 17:00–19:00 was selected to administrate Rus for further mechanism study and Nrf2 blocker group was administrated all-trans-retinoic acid (ATRA) at 14:00 for 3 days. Administration of Rus reduced cerebral infarcted volume, ameliorated the behavior score and upregulated the mRNA and protein expression of Per1, Bmal1, Clock, Rev-erbα, transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1). Administration of Rus during 17:00–19:00 had better preventive effect than other three time points. Combined administration of ATRA blunted the preventive effect of Rus. The preventive effect of Rus is affected by the time of administration, which was regulated by Nrf2 pathway. Taken together, we provide solid evidence to suggest that different administration time point affect the effectiveness of Rus in alleviating IRI.
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