Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
Dihydroartemisinin (DHA) has been found to inhibit the expression of von Willebrand factor (VWF), a marker of endothelial cell injury, but its mechanism in cerebral ischemia/reperfusion (I/R) injury remains obscure. In this study, I/R model was constructed through middle cerebral artery occlusion (M...
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| Format: | Article |
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De Gruyter
2023-07-01
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| Series: | Open Medicine |
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| Online Access: | https://doi.org/10.1515/med-2023-0698 |
| _version_ | 1797784125400154112 |
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| author | Duan Qi Wu Junxia |
| author_facet | Duan Qi Wu Junxia |
| author_sort | Duan Qi |
| collection | DOAJ |
| description | Dihydroartemisinin (DHA) has been found to inhibit the expression of von Willebrand factor (VWF), a marker of endothelial cell injury, but its mechanism in cerebral ischemia/reperfusion (I/R) injury remains obscure. In this study, I/R model was constructed through middle cerebral artery occlusion (MCAO) in rats, followed by DHA administration. The effect of DHA on rat cerebral I/R injury was investigated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, TUNEL staining, and Western blot. Brain microvascular endothelial cells (BMVECs) isolated from newborn rats were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R), and then treated with DHA. The results showed that MCAO treatment induced infarction, nerve cell apoptosis, and brain tissue impairment in rats, which was mitigated by DHA. OGD/R inhibited viability and accelerated apoptosis of BMVECs, which was alleviated by DHA. I/R procedures or OGD/R up-regulated expressions of VWF, ATG7, Beclin1, and LC3-II/LC3-I ratio, while down-regulating Occludin, Claudin-5, ZO-1, P62, SIRT1, and FOXO1 expressions in vivo and in vitro; however, these effects of I/R procedures or OGD/R were offset by DHA. VWF overexpression reversed the above effects of DHA on OGD/R-induced BMVECs. In summary, DHA ameliorates cerebral I/R injury in rats by reducing VWF level and activating autophagy-mediated SIRT1/FOXO1 signaling pathway. |
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| language | English |
| last_indexed | 2024-03-13T00:35:34Z |
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| spelling | doaj.art-2cd47ad516b4454ea0f9c27c5b84ed532023-07-10T06:03:58ZengDe GruyterOpen Medicine2391-54632023-07-0118131203110.1515/med-2023-0698Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathwayDuan Qi0Wu Junxia1Emergency Department, Nantong Rich Hospital, Nantong, Jiangsu, 226006, ChinaEmergency Department, The Sixth People’s Hospital of Nantong, No. 500 Yonghe Road, Gangzha District, Nantong, Jiangsu, 226000, ChinaDihydroartemisinin (DHA) has been found to inhibit the expression of von Willebrand factor (VWF), a marker of endothelial cell injury, but its mechanism in cerebral ischemia/reperfusion (I/R) injury remains obscure. In this study, I/R model was constructed through middle cerebral artery occlusion (MCAO) in rats, followed by DHA administration. The effect of DHA on rat cerebral I/R injury was investigated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, TUNEL staining, and Western blot. Brain microvascular endothelial cells (BMVECs) isolated from newborn rats were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R), and then treated with DHA. The results showed that MCAO treatment induced infarction, nerve cell apoptosis, and brain tissue impairment in rats, which was mitigated by DHA. OGD/R inhibited viability and accelerated apoptosis of BMVECs, which was alleviated by DHA. I/R procedures or OGD/R up-regulated expressions of VWF, ATG7, Beclin1, and LC3-II/LC3-I ratio, while down-regulating Occludin, Claudin-5, ZO-1, P62, SIRT1, and FOXO1 expressions in vivo and in vitro; however, these effects of I/R procedures or OGD/R were offset by DHA. VWF overexpression reversed the above effects of DHA on OGD/R-induced BMVECs. In summary, DHA ameliorates cerebral I/R injury in rats by reducing VWF level and activating autophagy-mediated SIRT1/FOXO1 signaling pathway.https://doi.org/10.1515/med-2023-0698cerebral ischemia/reperfusion injurybrain microvascular endothelial cellsdihydroartemisininvon willebrand factorsirt1/foxo1 pathwayautophagy |
| spellingShingle | Duan Qi Wu Junxia Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway Open Medicine cerebral ischemia/reperfusion injury brain microvascular endothelial cells dihydroartemisinin von willebrand factor sirt1/foxo1 pathway autophagy |
| title | Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway |
| title_full | Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway |
| title_fullStr | Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway |
| title_full_unstemmed | Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway |
| title_short | Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway |
| title_sort | dihydroartemisinin ameliorates cerebral i r injury in rats via regulating vwf and autophagy mediated sirt1 foxo1 pathway |
| topic | cerebral ischemia/reperfusion injury brain microvascular endothelial cells dihydroartemisinin von willebrand factor sirt1/foxo1 pathway autophagy |
| url | https://doi.org/10.1515/med-2023-0698 |
| work_keys_str_mv | AT duanqi dihydroartemisininamelioratescerebralirinjuryinratsviaregulatingvwfandautophagymediatedsirt1foxo1pathway AT wujunxia dihydroartemisininamelioratescerebralirinjuryinratsviaregulatingvwfandautophagymediatedsirt1foxo1pathway |