Sodium formononetin-3'-sulphonate alleviates cerebral ischemia–reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosis
Abstract Background Sodium formononetin-3ʹ-sulphonate (Sul-F) may alleviate I/R injury in vivo with uncertain mechanism. Endoplasmic reticulum (ER) stress-mediated apoptosis participates in the process of cerebral ischemia‐reperfusion (I/R) injury. Our aim is to figure out the effect of Sul-F on cer...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
|
| Series: | BMC Neuroscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12868-022-00762-4 |
| _version_ | 1811302043432779776 |
|---|---|
| author | Yue Bai Zhiwei He Weisong Duan He Gu Kefeng Wu Wei Yuan Wenkang Liu Huaipeng Huang Yanan Li |
| author_facet | Yue Bai Zhiwei He Weisong Duan He Gu Kefeng Wu Wei Yuan Wenkang Liu Huaipeng Huang Yanan Li |
| author_sort | Yue Bai |
| collection | DOAJ |
| description | Abstract Background Sodium formononetin-3ʹ-sulphonate (Sul-F) may alleviate I/R injury in vivo with uncertain mechanism. Endoplasmic reticulum (ER) stress-mediated apoptosis participates in the process of cerebral ischemia‐reperfusion (I/R) injury. Our aim is to figure out the effect of Sul-F on cerebral I/R injury and to verify whether it works through suppressing ER stress-mediated apoptosis. Results The cerebral lesions of middle cerebral artery occlusion (MCAO) model in SD rats were aggravated after 24 h of reperfusion, including impaired neurological function, increased infarct volume, intensified inflammatory response and poor cell morphology. After intervention, the edaravone (EDA, 3 mg/kg) group and Sul-F high-dose (Sul-F-H, 80 mg/kg) group significantly alleviated I/R injury via decreasing neurological score, infarct volume and the serum levels of inflammatory factors (TNF-α, IL-1β and IL-6), as well as alleviating pathological injury. Furthermore, the ER stress level and apoptosis rate were elevated in the ischemic penumbra of MCAO group, and were significantly blocked by EDA and Sul-F-H. In addition, EDA and Sul-F-H significantly down-regulated the ER stress related PERK/eIF2α/ATF4 and IRE1 signal pathways, which led to reduced cell apoptosis rate compared with the MCAO group. Furthermore, there was no difference between the EDA and Sul-F-H group in terms of therapeutic effect on cerebral I/R injury, indicating a therapeutic potential of Sul-F for ischemic stroke. Conclusions Sul-F-H can significantly protects against cerebral I/R injury through inhibiting ER stress-mediated apoptosis in the ischemic penumbra, which might be a novel therapeutic target for ischemic stroke. |
| first_indexed | 2024-04-13T07:20:53Z |
| format | Article |
| id | doaj.art-0b53937cacb54c4f90d1801638249f2e |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-04-13T07:20:53Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-0b53937cacb54c4f90d1801638249f2e2022-12-22T02:56:37ZengBMCBMC Neuroscience1471-22022022-12-0123111410.1186/s12868-022-00762-4Sodium formononetin-3'-sulphonate alleviates cerebral ischemia–reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosisYue Bai0Zhiwei He1Weisong Duan2He Gu3Kefeng Wu4Wei Yuan5Wenkang Liu6Huaipeng Huang7Yanan Li8Department of Internal Medicine, Shijiazhuang Pingan Hospital, Hebei Medical UniversityDepartment of Internal Medicine, Shijiazhuang Pingan Hospital, Hebei Medical UniversityNeurological Laboratory of Hebei Province, The Second Hospital of Hebei Medical UniversityDepartment of Internal Medicine, Shijiazhuang Pingan Hospital, Hebei Medical UniversityDepartment of Internal Medicine, Shijiazhuang Pingan Hospital, Hebei Medical UniversityDepartment of Internal Medicine, Shijiazhuang Pingan Hospital, Hebei Medical UniversityDepartment of Internal Medicine, Shijiazhuang Pingan Hospital, Hebei Medical UniversityDepartment of Internal Medicine, Shijiazhuang Pingan Hospital, Hebei Medical UniversityDepartment of Clinical Laboratory Diagnosis, Shijiazhuang Pingan Hospital, Hebei Medical UniversityAbstract Background Sodium formononetin-3ʹ-sulphonate (Sul-F) may alleviate I/R injury in vivo with uncertain mechanism. Endoplasmic reticulum (ER) stress-mediated apoptosis participates in the process of cerebral ischemia‐reperfusion (I/R) injury. Our aim is to figure out the effect of Sul-F on cerebral I/R injury and to verify whether it works through suppressing ER stress-mediated apoptosis. Results The cerebral lesions of middle cerebral artery occlusion (MCAO) model in SD rats were aggravated after 24 h of reperfusion, including impaired neurological function, increased infarct volume, intensified inflammatory response and poor cell morphology. After intervention, the edaravone (EDA, 3 mg/kg) group and Sul-F high-dose (Sul-F-H, 80 mg/kg) group significantly alleviated I/R injury via decreasing neurological score, infarct volume and the serum levels of inflammatory factors (TNF-α, IL-1β and IL-6), as well as alleviating pathological injury. Furthermore, the ER stress level and apoptosis rate were elevated in the ischemic penumbra of MCAO group, and were significantly blocked by EDA and Sul-F-H. In addition, EDA and Sul-F-H significantly down-regulated the ER stress related PERK/eIF2α/ATF4 and IRE1 signal pathways, which led to reduced cell apoptosis rate compared with the MCAO group. Furthermore, there was no difference between the EDA and Sul-F-H group in terms of therapeutic effect on cerebral I/R injury, indicating a therapeutic potential of Sul-F for ischemic stroke. Conclusions Sul-F-H can significantly protects against cerebral I/R injury through inhibiting ER stress-mediated apoptosis in the ischemic penumbra, which might be a novel therapeutic target for ischemic stroke.https://doi.org/10.1186/s12868-022-00762-4FormononetinCerebral ischemia-reperfusion injuryEndoplasmic reticulum stressCell apoptosisIschemic penumbraStroke |
| spellingShingle | Yue Bai Zhiwei He Weisong Duan He Gu Kefeng Wu Wei Yuan Wenkang Liu Huaipeng Huang Yanan Li Sodium formononetin-3'-sulphonate alleviates cerebral ischemia–reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosis BMC Neuroscience Formononetin Cerebral ischemia-reperfusion injury Endoplasmic reticulum stress Cell apoptosis Ischemic penumbra Stroke |
| title | Sodium formononetin-3'-sulphonate alleviates cerebral ischemia–reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosis |
| title_full | Sodium formononetin-3'-sulphonate alleviates cerebral ischemia–reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosis |
| title_fullStr | Sodium formononetin-3'-sulphonate alleviates cerebral ischemia–reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosis |
| title_full_unstemmed | Sodium formononetin-3'-sulphonate alleviates cerebral ischemia–reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosis |
| title_short | Sodium formononetin-3'-sulphonate alleviates cerebral ischemia–reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosis |
| title_sort | sodium formononetin 3 sulphonate alleviates cerebral ischemia reperfusion injury in rats via suppressing endoplasmic reticulum stress mediated apoptosis |
| topic | Formononetin Cerebral ischemia-reperfusion injury Endoplasmic reticulum stress Cell apoptosis Ischemic penumbra Stroke |
| url | https://doi.org/10.1186/s12868-022-00762-4 |
| work_keys_str_mv | AT yuebai sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis AT zhiweihe sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis AT weisongduan sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis AT hegu sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis AT kefengwu sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis AT weiyuan sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis AT wenkangliu sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis AT huaipenghuang sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis AT yananli sodiumformononetin3sulphonatealleviatescerebralischemiareperfusioninjuryinratsviasuppressingendoplasmicreticulumstressmediatedapoptosis |