Xueying Guan1, Xiaolei Li2, Xuejiao Yang3, Junwei Yan3, Pilong Shi1, Lina Ba1, Yonggang Cao4, Peng Wang5. 1. Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, China. 2. Department of Scientific Research, Third Affiliated Hospital of Gui zhou Medical University, Du yun, Gui zhou, 558000, China. 3. Department of Vascular Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266003, China. 4. Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, China. Electronic address: yonggangcaodr2014@163.com. 5. Department of Physiology, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319, China. Electronic address: wangpeng810122@126.com.
Abstract
OBJECTIVE: Cerebral ischemia is the most common type of neuronal injury and is characterized by a reduction in the function and number of hippocampal neurons. Carvacrol has a significant neuroprotective effect in cerebral ischemia. However, the mechanisms by which carvacrol affects cerebral ischemia, especially with respect to the regulation of neuronal damage by iron levels, have never been systematically studied. This study aimed to reveal the mechanisms by which carvacrol protects against hippocampal neuron impairment after ischemic stroke in gerbils. MATERIALS AND METHODS: The Morris water maze test was performed to evaluate learning and memory impairments. Iron ion content and oxidative stress index were detected by the kit. MTT assay was performed to assess the cell viability. The morphology and molecular characteristics were detected by electron micrographs and western blot. RESULTS: In the present study, we demonstrated the neuroprotective effects of carvacrol in vivo and in vitro. The Morris water maze test showed that the learning and memory abilities of the gerbils treated with carvacrol were significantly improved. Lipid peroxide injury was evaluated by measuring the levels of lipid peroxide biomarkers; the results indicated that carvacrol decreased the level of lipid peroxide in ischemic gerbil brain tissue. Histopathological examinations and western blotting were performed to evaluate injury in neurons, and carvacrol reduced cell death. Moreover, ferroptosis in the hippocampus was evaluated by measuring the levels of proteins involved in this iron-dependent form of regulated cell death. These results indicated that carvacrol reduced cell death and that carvacrol inhibited ferroptosis by increasing the expression of glutathione peroxidase 4(GPx4). This study showed that carvacrol may be a valuable drug for treating cerebral ischemia. CONCLUSION: Carvacrol provides protection for hippocampal neurons against I/R in gerbils by inhibiting ferroptosis through increasing the expression of GPx4.
OBJECTIVE:Cerebral ischemia is the most common type of neuronal injury and is characterized by a reduction in the function and number of hippocampal neurons. Carvacrol has a significant neuroprotective effect in cerebral ischemia. However, the mechanisms by which carvacrol affects cerebral ischemia, especially with respect to the regulation of neuronal damage by iron levels, have never been systematically studied. This study aimed to reveal the mechanisms by which carvacrol protects against hippocampal neuron impairment after ischemic stroke in gerbils. MATERIALS AND METHODS: The Morris water maze test was performed to evaluate learning and memory impairments. Iron ion content and oxidative stress index were detected by the kit. MTT assay was performed to assess the cell viability. The morphology and molecular characteristics were detected by electron micrographs and western blot. RESULTS: In the present study, we demonstrated the neuroprotective effects of carvacrol in vivo and in vitro. The Morris water maze test showed that the learning and memory abilities of the gerbils treated with carvacrol were significantly improved. Lipid peroxideinjury was evaluated by measuring the levels of lipid peroxide biomarkers; the results indicated that carvacrol decreased the level of lipid peroxide in ischemic gerbil brain tissue. Histopathological examinations and western blotting were performed to evaluate injury in neurons, and carvacrol reduced cell death. Moreover, ferroptosis in the hippocampus was evaluated by measuring the levels of proteins involved in this iron-dependent form of regulated cell death. These results indicated that carvacrol reduced cell death and that carvacrol inhibited ferroptosis by increasing the expression of glutathione peroxidase 4(GPx4). This study showed that carvacrol may be a valuable drug for treating cerebral ischemia. CONCLUSION:Carvacrol provides protection for hippocampal neurons against I/R in gerbils by inhibiting ferroptosis through increasing the expression of GPx4.