Breviscapine Alleviates Cognitive Impairments Induced by Transient Cerebral Ischemia/Reperfusion through Its Anti-Inflammatory and Anti-Oxidant Properties in a Rat Model

Abstract

Cerebral ischemia/reperfusion (I/R)-induced injury is a common phenomenon of stroke, and the effective treatment for I/R-induced brain tissue damage is limited. Breviscapine has been widely used in China as herbal medicine to treat cardiovascular diseases for hundreds of years and has been demonstrated to possess potent cardiovascular pharmacological effects. This study aims to investigate the neuroprotective effect of breviscapine on cerebral I/R-induced injury. The rat model of middle cerebral artery occlusion (MCAO) was applied in our study. The cerebral I/R rats received multiple injections of breviscapine. All rats were subject to neurological behavior tests by open field test and Morris water maze test. The pro-inflammatory cytokines and oxidative stress marker levels were determined by ELISA and colorimetric analysis, respectively. We demonstrated that administration of breviscapine dose-dependently ameliorated cerebral I/R-induced injury and improved the neurological performance of cerebral I/R rats. Further studies illustrated that breviscapine treatment effectively attenuated inflammatory cytokine expression, reduced oxidative stress, and pro-apoptosis protein expression and inhibited the activation of NF-κB signaling and microglia in the I/R injury tissues. Breviscapine may serve as a single drug or a promising adjuvant that can be used in conjunction with other medicine for the treatment of cerebral I/R-induced injury.

Challenges and Improvements of Novel Therapies for Ischemic Stroke

“…Apart from these active components mentioned, there are still many active ingredients that are effective in the treatment of stroke in preclinical studies and are under clinical studies ( Supplementary Table S1 ). For example, breviscapine could alleviate cognitive impairments and neuro defects caused by stroke through its anti-inflammatory and antioxidant, promoting autophagy ( Li et al, 2020 ). Timosaponin B and scutellarein had neuroprotective effects against stroke by their antithrombotic, antiplatelet, and anticoagulation effects ( Dong et al, 2019 ).…”

Diosmetin alleviates cerebral ischemia‐reperfusion injury through Keap1‐mediated Nrf2/ARE signaling pathway activation and NLRP3 inflammasome inhibition

“…6 It was reported that administration of breviscapine ameliorated CIR-induced neurological injury and improved the neurological performance in MCAO rats through its anti-inflammatory and anti-oxidant properties. 7 Diosmetin is a natural flavonoid compound present in citrus fruit. More notably, diosmetin has been found to play critical roles in ischemia-reperfusion (IR)induced diseases through its antioxidant and anti-inflammatory effects.…”

“…Morin alleviated cerebral damage and protected the blood–brain barrier integrity by attenuating oxidative stress, inflammation, and apoptosis in a middle cerebral artery occlusion (MCAO) and reperfusion model 6 . It was reported that administration of breviscapine ameliorated CIR‐induced neurological injury and improved the neurological performance in MCAO rats through its anti‐inflammatory and anti‐oxidant properties 7 . Diosmetin is a natural flavonoid compound present in citrus fruit.…”

The Signaling Pathways and Targets of Natural Compounds from Traditional Chinese Medicine in Treating Ischemic Stroke

“…Salvianolic acid D, a polyphenol component of Salvia miltiorrhiza Bunge, inhibits NF-κB activation and inflammatory factor release mediated by HMGB1-TLR4 signaling and attenuates HMGB1-mediated inflammatory response by inhibiting TLR4/MyD88/NF-κB signaling pathway [ 36 ]. Furthormore, other natural compounds such as triptolide, β-patchoulene, ginkgetin, tanshinone IIA, breviscapine, diosgenin, icariin, and berberine can also exert a protective effect against ischemic brain injury by inhibiting the NF-κB signaling pathway [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. The NF-κB signaling pathway and the chemical structure of natural compounds are shown in Figure 2 .…”