Abstract
Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R). Ischemia and reperfusion-induced injury or apoptosis inhibition in human brain tissue may exert an irreplaceable protective effect on ischemic nerves. This process has particular significance for the treatment of stroke patients. However, the development of neuroprotective drugs remains challenging. Radix Scrophulariae, traditionally considered a valuable medicine, has been discovered to have neuroprotective effects. To explore the neuroprotective effects of an aqueous extract of Radix Scrophulariae (RSAE) on cerebral ischemia/reperfusion and their underlying mechanisms, oxygen-glucose deprivation and reperfusion (OGD/R)-induced PC12 cells were used, and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. In vitro results showed that 12.5 μg/mL RSAE markedly improved cell viability; inhibited LDH leakage; increased SOD, GSH-Px and CAT enzyme activity; stabilized the mitochondrial membrane potential; and reduced OGD-induced cell injury and apoptosis. Additionally, in vivo results preliminarily suggested that in MCAO/R model mice, RSAE treatments attenuated infarct volume; reduced brain water content and nitric oxide (NO) and malondialdehyde (MDA) concentrations; inhibited I/R-induced neurological deficits; reduced the levels of lactate dehydrogenase (LDH) leakage release; improved antioxidant capacity by upregulating SOD, GSH-Px and CAT enzyme activity; and reduced neuronal apoptosis, necrosis and loss of neurons. Moreover, it was found that RSAE upregulated the expression of Bcl-2 and downregulated the expression of Bax. In addition, the phosphorylation levels of MAPK signal pathways were elucidated via western blot analysis and immunohistochemical evaluation. In summary, this study investigated the neuroprotective effects and potential mechanisms of RSAE on focal cerebral I/R injury in mice. Radix Scrophulariae has been previously identified as a potential neuroprotective natural plant. Hence, our results may offer insight into discovering new active compounds or drugs for the treatment of ischemic stroke. Many new natural active chemicals in this extract may be discovered by chemical separation and identification and may provide new insights into therapeutic targets in stroke patients.
Highlights
Ischemic stroke is a clinically common cerebrovascular disease accounting for 70 to 80% of all cerebrovascular patients; approximately 15 million people worldwide suffer from stroke each year, resulting in approximately 5 million deaths and making it a primary cause of disability and death worldwide [1,2]
To explore better treatment options for ischemic stroke and reperfusion injury, researchers have carried out extensive studies on its pathogenesis; proposed a set of theories [4,5] mainly including energy metabolism disorders, oxidative stress, glutamate toxicity, Ca2+ overload, excessive nitric oxide (NO) synthesis, and apoptosis; and developing a series of new drugs [5], such as recombinant tissue plasminogen activator (r-TPA), aspirin and heparin
The results showed that the brain water content (BWC) distinctly increased in the ischemic brain brain hemisphere hemisphere of of the group, and and this this increase increase was was significantly significantly reduced reduced by by ischemic the middle cerebral artery occlusion/reperfusion (MCAO/R)
Summary
Ischemic stroke is a clinically common cerebrovascular disease accounting for 70 to 80% of all cerebrovascular patients; approximately 15 million people worldwide suffer from stroke each year, resulting in approximately 5 million deaths and making it a primary cause of disability and death worldwide [1,2]. The primary concern of clinical treatment for ischemic stroke is to restore blood and oxygen supply to the ischemic brain tissue as soon as possible. To explore better treatment options for ischemic stroke and reperfusion injury, researchers have carried out extensive studies on its pathogenesis; proposed a set of theories [4,5] mainly including energy metabolism disorders, oxidative stress, glutamate toxicity, Ca2+ overload, excessive NO synthesis, and apoptosis; and developing a series of new drugs [5], such as recombinant tissue plasminogen activator (r-TPA), aspirin and heparin. The management of acute ischemic stroke has not made significant strides since the introduction of recombinant tissue plasminogen activator (r-TPA) two decades ago [3], and r-TPA is the only thrombolytic agent approved by the US Food and Drug Administration for stroke treatment [6]. Since its therapeutic time window (TTW) is narrow, r-TPA treatment for stroke is suitable for only a limited percentage of stroke patients (
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