Application and prospects of butylphthalide for the treatment of neurologic diseases

Abstract

Objective The 3- N -butylphthalide (NBP) comprises one of the chemical constituents of celery oil. It has a series of pharmacologic mechanisms including reconstructing microcirculation, protecting mitochondrial function, inhibiting oxidative stress, inhibiting neuronal apoptosis, etc. Based on the complex multi-targets of pharmacologic mechanisms of NBP, the clinical application of NBP is increasing and more clinical researches and animal experiments are also focused on NBP. The aim of this review was to comprehensively and systematically summarize the application of NBP on neurologic diseases and briefly summarize its application to non-neurologic diseases. Moreover, recent progress in experimental models of NBP on animals was summarized. Data sources Literature was collected from PubMed and Wangfang database until November 2018, using the search terms including “3- N -butylphthalide,” “microcirculation,” “mitochondria,” “ischemic stroke,” “Alzheimer disease,” “vascular dementia,” “Parkinson disease,” “brain edema,” “CO poisoning,” “traumatic central nervous system injury,” “autoimmune disease,” “amyotrophic lateral sclerosis,” “seizures,” “diabetes,” “diabetic cataract,” and “atherosclerosis.” Study selection Literature was mainly derived from English articles or articles that could be obtained with English abstracts and partly derived from Chinese articles. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors’ files. Results NBP has become an important adjunct for ischemic stroke. In vascular dementia, the clinical application of NBP to treat severe cognitive dysfunction syndrome caused by the hypoperfusion of brain tissue during cerebrovascular disease is also increasing. Evidence also suggests that NBP has a therapeutic effect for neurodegenerative diseases. Many animal experiments have found that it can also improve symptoms in other neurologic diseases such as epilepsy, cerebral edema, and decreased cognitive function caused by severe acute carbon monoxide poisoning. Moreover, NBP has therapeutic effects for diabetes, diabetes-induced cataracts, and non-neurologic diseases such as atherosclerosis. Mechanistically, NBP mainly improves microcirculation and protects mitochondria. Its broad pharmacologic effects also include inhibiting oxidative stress, nerve cell apoptosis, inflammatory responses, and anti-platelet and anti-thrombotic effects. Conclusions The varied pharmacologic mechanisms of NBP involve many complex molecular mechanisms; however, there many unknown pharmacologic effects await further study.

Mitochondrial Dysfunctions: A Red Thread across Neurodegenerative Diseases

“…Other molecules, which are not specific for the treatment of neurodegenerative diseases, can counteract mitochondrial alterations, preventing a wide range of altered mechanisms. For instance, 3-N-butylphthalide (NBP), a compound widely employed in the treatment of ischemic stroke in China thanks to its ability in restoring microcirculation [227], can (i) maintain mitochondria permeability and dynamics (preventing mitochondria swelling), (ii) improve mitochondria bioenergetics (increasing complex IV activity), (iii) prevent cytochrome c release and caspase-dependent apoptosis, and (iv) counteract ROS production. Indeed, most of these effects have been observed on in vitro and in vivo PD models, determining neuroprotection and behavioral improvement [228,229] and a randomized controlled trial has demonstrated NBP efficacy in improving motor symptom and sleep quality of PD patients [230].…”

Effect of butylphthalide on new cerebral microbleeds in patients with acute ischemic stroke

“…Previous studies indicated that dl-3-N-butylphthalide (NBP) not only improved neurological function, but also contributed to the long-term outcomes. [ 13 ] The mechanisms of NBP for ischemic stroke treatment may involve many complex molecular mechanisms, including anti-oxidant, anti-thrombosis, anti-apoptosis, anti-inflammation, protection of mitochondria, and so on. [ 14 ]…”

Efficacy and safety of butylphthalide as adjunctive therapy for vascular dementia

“…Butylphthalide was first extracted from the celery seed and was discovered within the last few decades. [ 10 ] The main pharmacologic effects of butylphthalide include antiplatelet aggregation effect, mitochondria protect effect, antiapoptotic effect, and so on. [ 11 – 14 ] Based on the therapeutic property of this compound, butylphthalide was artificially synthesized later in China and approved by the China Food and Drug Administration for ischemic stroke and neuro impairment induced by ischemic stroke.…”

“…[ 11 – 14 ] Based on the therapeutic property of this compound, butylphthalide was artificially synthesized later in China and approved by the China Food and Drug Administration for ischemic stroke and neuro impairment induced by ischemic stroke. [ 10 ] Due to its promising pharmacological effect and good safety profile, butylphthalide is widely used as an adjunctive therapy for ischemic stroke. [ 15 ] It is also used for neurodegenerative diseases such as Alzheimer disease and Parkinson disease.…”

“…[ 15 ] It is also used for neurodegenerative diseases such as Alzheimer disease and Parkinson disease. [ 10 ] Butylphthalide is believed to improve vascular dementia management through its antioxidant, anti-apoptotic effects and through reduction of A β deposits. [ 11 ] It is also recognized as hopeful adjunctive therapy for vascular dementia.…”