Ginsenoside-Mc1 reduces cerebral ischemia-reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative/endoplasmic reticulum stress
The neuroprotective effect of ginsenoside-Mc1 (GMc1) in hyperlipidemic rats in the setting of cerebral ischemiareperfusion injury (I/RI), as well as the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels and oxidative/ endoplasmic reticulum (ER) stress, was investigated. Hyperlipidemi...
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University of Belgrade, University of Novi Sad
2022-01-01
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| Series: | Archives of Biological Sciences |
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| Online Access: | http://www.doiserbia.nb.rs/img/doi/0354-4664/2022/0354-46642200015W.pdf |
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| author | Wang Min Li Danni |
| author_facet | Wang Min Li Danni |
| author_sort | Wang Min |
| collection | DOAJ |
| description | The neuroprotective effect of ginsenoside-Mc1 (GMc1) in hyperlipidemic rats in the setting of cerebral ischemiareperfusion injury (I/RI), as well as the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels and oxidative/ endoplasmic reticulum (ER) stress, was investigated. Hyperlipidemia (8 weeks) was induced by a high-fat diet in Sprague Dawley rats. GMc1 (10 mg/kg, i.p.) was given to hyperlipidemic rats daily for one month before I/RI. Rat brains were subjected to 2 h of local ischemia followed by 24 h reperfusion. The cerebral infarcted injury was measured by triphenyltetrazolium chloride staining and the levels of oxidative stress indicators were detected by ELISA and spectrophotometry. A fluorometric technique was employed to evaluate mitochondrial function. Western blotting was used to detect changes in the expression of ER stress proteins. GMc1 reduced cerebral infarct volume in hyperlipidemic rats in comparison to untreated ones (P<0.01). GMc1 reduced cerebral infarct volume in hyperlipidemic rats as compared to untreated rats (P<0.01). GMc1 significantly decreased mitochondrial membrane depolarization, mitochondrial reactive oxygen species (mitoROS) and malondialdehyde levels (P<0.01), while increasing the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) (P<0.001). GMc1 administration reduced the expression of ER stress markers, including phosphorylated (p)-endoplasmic reticulum kinase (PERK), p-eukaryotic translation initiation factor 2 subunit 1 (elF2α), and C/EBP homologous protein (CHOP). Inhibition of mitoKATP channels with hydroxydecanoate significantly eliminated the protective impacts of GMc1 in hyperlipidemic rats subjected to cerebral I/RI. The neuroprotective effect of GMc1 preconditioning was remarkably improved by increasing mitoKATP channel activity and decreasing oxidative and ER stress levels in hyperlipidemic rats, implying that this compound could be an appropriate candidate for reducing cerebral I/RI in comorbidities. |
| first_indexed | 2024-12-11T16:24:15Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 0354-4664 1821-4339 |
| language | English |
| last_indexed | 2024-12-11T16:24:15Z |
| publishDate | 2022-01-01 |
| publisher | University of Belgrade, University of Novi Sad |
| record_format | Article |
| series | Archives of Biological Sciences |
| spelling | doaj.art-6e1f667c82bd49f083c21d8fbd75268a2022-12-22T00:58:46ZengUniversity of Belgrade, University of Novi SadArchives of Biological Sciences0354-46641821-43392022-01-0174215916810.2298/ABS220212015W0354-46642200015WGinsenoside-Mc1 reduces cerebral ischemia-reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative/endoplasmic reticulum stressWang Min0Li Danni1Department of Neurology, Central Hospital Affiliated to Shandong First Medical University, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, ChinaDepartment of Neurology, Central Hospital Affiliated to Shandong First Medical University, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, ChinaThe neuroprotective effect of ginsenoside-Mc1 (GMc1) in hyperlipidemic rats in the setting of cerebral ischemiareperfusion injury (I/RI), as well as the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels and oxidative/ endoplasmic reticulum (ER) stress, was investigated. Hyperlipidemia (8 weeks) was induced by a high-fat diet in Sprague Dawley rats. GMc1 (10 mg/kg, i.p.) was given to hyperlipidemic rats daily for one month before I/RI. Rat brains were subjected to 2 h of local ischemia followed by 24 h reperfusion. The cerebral infarcted injury was measured by triphenyltetrazolium chloride staining and the levels of oxidative stress indicators were detected by ELISA and spectrophotometry. A fluorometric technique was employed to evaluate mitochondrial function. Western blotting was used to detect changes in the expression of ER stress proteins. GMc1 reduced cerebral infarct volume in hyperlipidemic rats in comparison to untreated ones (P<0.01). GMc1 reduced cerebral infarct volume in hyperlipidemic rats as compared to untreated rats (P<0.01). GMc1 significantly decreased mitochondrial membrane depolarization, mitochondrial reactive oxygen species (mitoROS) and malondialdehyde levels (P<0.01), while increasing the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) (P<0.001). GMc1 administration reduced the expression of ER stress markers, including phosphorylated (p)-endoplasmic reticulum kinase (PERK), p-eukaryotic translation initiation factor 2 subunit 1 (elF2α), and C/EBP homologous protein (CHOP). Inhibition of mitoKATP channels with hydroxydecanoate significantly eliminated the protective impacts of GMc1 in hyperlipidemic rats subjected to cerebral I/RI. The neuroprotective effect of GMc1 preconditioning was remarkably improved by increasing mitoKATP channel activity and decreasing oxidative and ER stress levels in hyperlipidemic rats, implying that this compound could be an appropriate candidate for reducing cerebral I/RI in comorbidities.http://www.doiserbia.nb.rs/img/doi/0354-4664/2022/0354-46642200015W.pdfginsenoside-mc1atp-sensitive potassium channelendoplasmic reticulum stresshyperlipidemiaischemia-reperfusion injury |
| spellingShingle | Wang Min Li Danni Ginsenoside-Mc1 reduces cerebral ischemia-reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative/endoplasmic reticulum stress Archives of Biological Sciences ginsenoside-mc1 atp-sensitive potassium channel endoplasmic reticulum stress hyperlipidemia ischemia-reperfusion injury |
| title | Ginsenoside-Mc1 reduces cerebral ischemia-reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative/endoplasmic reticulum stress |
| title_full | Ginsenoside-Mc1 reduces cerebral ischemia-reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative/endoplasmic reticulum stress |
| title_fullStr | Ginsenoside-Mc1 reduces cerebral ischemia-reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative/endoplasmic reticulum stress |
| title_full_unstemmed | Ginsenoside-Mc1 reduces cerebral ischemia-reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative/endoplasmic reticulum stress |
| title_short | Ginsenoside-Mc1 reduces cerebral ischemia-reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative/endoplasmic reticulum stress |
| title_sort | ginsenoside mc1 reduces cerebral ischemia reperfusion injury in hyperlipidemia through mitochondrial improvement and attenuation of oxidative endoplasmic reticulum stress |
| topic | ginsenoside-mc1 atp-sensitive potassium channel endoplasmic reticulum stress hyperlipidemia ischemia-reperfusion injury |
| url | http://www.doiserbia.nb.rs/img/doi/0354-4664/2022/0354-46642200015W.pdf |
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