DL-3-n-Butylphthalide, an Anti-Oxidant Agent, Prevents Neurological Deficits and Cerebral Injury Following Stroke per Functional Analysis, Magnetic Resonance Imaging and Histological Assessment

Abstract

DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.

Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

“…The positive effects of NBP on cerebral ischemia, including improvement of microcirculation and energy metabolism, reduction of oxidative damage and neuronal apoptosis and inhibition of the inflammatory response, have been verified in experimental models and pharmacodynamic studies (1)(2)(3)(4)(5). Our previous studies demonstrated that NBP significantly inhibits caspase-3-mediated apoptosis, and decreases stroke-induced neuron loss and autophagic activity following cerebral ischemia in diabetic rats (22,23); and attenuates amyloid-β-induced activation of Table V.…”

“…The racemic compound DL-3-n-butylphthalide (NBP), which has multiple effects on various pathophysiological processes, is considered to be beneficial for the treatment of ischemic stroke, since it has been shown to protect neuronal cells against ischemia-induced brain damage and neurotoxic damage, improve cerebral blood flow, decrease brain edema and preserve the blood brain barrier (1)(2)(3)(4)(5). Cerebrolysin is a peptide-containing preparation that also exerts beneficial effects on ischemic stroke; preclinical studies have shown that Cerebrolysin substantially improves neurological outcome and promotes neurological functional recovery following ischemia by preventing cell death, the formation of free radicals, inflammation and by counteracting excitotoxicity (6)(7)(8)(9).…”

The novel targets of DL-3-n-butylphthalide predicted by similarity ensemble approach in combination with molecular docking study

“…Recently, studies also show that NBP has a therapeutic effect on various neurodegenerative diseases, especially vascular dementia and vascular cognitive impairment without dementia (1). In animal experiments, including our own investigations, NBP may reduce cerebral edema, decrease cerebral infarct volume, improve cerebral microcirculation, protect vascular endothelial cells, scavenge free radicals, protect mitochondria, reduce inflammation, inhibit neuronal apoptosis, counteract platelet aggregation, inhibit thrombosis and decrease the expression of β-amyloid protein and tau protein in the brain (1)(2)(3). Therefore, NBP may play a neuroprotective role by acting on multiple active targets.…”

N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons

“…Certain phthalide analogs have shown neuronal protection activity in brain injury and neurodegenerative diseases323334353637. As a major component of the Chinese herb Angelica sinensis , n-butylidenephthalide (Bdph) was tested for its ability to reduce amyloid aggregates in our DS-iPSC model.…”

“…Bdph has also been reported to improve dopaminergic neuron degeneration and α-synuclein accumulation in Caenorhabditis elegans models of Parkinson's disease32, though the underlying mechanism is still unclear. Notably, n-butylphthalide (NBP), which shares the same chemical structure as Bdph, shows strong neuron protection activity in acute brain ischemia and neural degenerative diseases3334353637. Treating AD with NBP activates MAPK53 and Akt signaling34 and attenuates Aβ accumulation, Tau overexpression and cognitive impairment in AD models.…”