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 functio...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展开更多
As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex- tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for isch...As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex- tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that I-3-n- butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cere- bral repetitive ischemia/reperfusion, and intragastrically administered I-3-n-butylphthalide daily for 28 consecutive days after ischemia/repedusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of I-3-n-butylphthalide, especially pretreatment with I-3-n- butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of I-3-n-butylphthalide can reduce loss of pyrami- dal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen- tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after I-3-n- butylphthalide treatment. Experimental findings demonstrate that I-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.展开更多
In the present study, a series of novel nitric oxide-hydrogen sulfide releasing derivatives of(S)-3-n-butylphthalide((S)-NBP) were designed, synthesized, and evaluated as potential antiplatelet agents. Compound NOSH-N...In the present study, a series of novel nitric oxide-hydrogen sulfide releasing derivatives of(S)-3-n-butylphthalide((S)-NBP) were designed, synthesized, and evaluated as potential antiplatelet agents. Compound NOSH-NBP-5 displayed the strongest activity in inhibiting the arachidonic acid(AA)- and adenosine diphosphate(ADP)-induced platelet aggregation in vitro, with 3.8- and 7.0-fold more effectiveness than(S)-NBP, respectively. Furthermore, NOSH-NBP-5 could release moderate levels of NO and H2 S, which would be beneficial in improving cardiovascular and cerebral circulation. Moreover, NOSH-NBP-5 could release(S)-NBP when incubated with rat brain homogenate. In conclusion, these findings may provide new insights into the development of novel antiplatelet agents for the treatment of thrombosis-related ischemic stroke.展开更多
A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic pe...A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic peripheral neuropathy. Therefore, this study investigated the effects of high glucose on proliferation, apoptosis, and 3-nitrotyrosine levels of Schwann cells treated with butylphthalide. In addition, we explored potential protective mechanisms of butylphthalide on peripheral nerves. Schwann cells were cultured in vitro with high glucose then stimulated with the peroxynitrite anion inhibitors uric acid and 3-n-butylphthalide for 48 hours. Cell Counting Kit-8 and flow cytometry were used to investigate the effects of uric acid and 3-n-butylphthalide on proliferation and apoptosis of Schwann cells exposed to a high glucose environment. Effects of uric acid and 3-n-butylphthalide on levels of 3-nitrotyrosine in Schwann cells were detected by enzyme-linked immunosorbent assay. The results indicated that Schwann cells cultured in high glucose showed decreased proliferation, but increased apoptosis and intracellular 3-nitrotyrosine levels. However, intervention with uric acid or 3-n-butylphthalide could increase proliferation of Schwann cells cultured in high glucose, and inhibited apoptosis and intracellular 3-nitrotyrosine levels. According to our data, 3-n-butylphthalide may inhibit cell nitrification and apoptosis, and promote cell proliferation, thereby reducing damage to Schwann cells caused by high glucose.展开更多
文摘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
基金supported by the National Natural Science Foundationof China, No. 81241037the Natural Science Foundationof Hebei Province, No.H2013307046
文摘As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex- tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that I-3-n- butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cere- bral repetitive ischemia/reperfusion, and intragastrically administered I-3-n-butylphthalide daily for 28 consecutive days after ischemia/repedusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of I-3-n-butylphthalide, especially pretreatment with I-3-n- butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of I-3-n-butylphthalide can reduce loss of pyrami- dal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen- tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after I-3-n- butylphthalide treatment. Experimental findings demonstrate that I-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.
基金supported by the National Natural Science Foundation for Young Scientists of China(Nos:21502071 and 21302068)the Natural Science Foundation of Jiangsu Province,China(Nos:BK20140154 and BK20130127)the Fundamental Research Funds for the Central Universities(Nos:JUSRP51411B and JUSRP51629B)
文摘In the present study, a series of novel nitric oxide-hydrogen sulfide releasing derivatives of(S)-3-n-butylphthalide((S)-NBP) were designed, synthesized, and evaluated as potential antiplatelet agents. Compound NOSH-NBP-5 displayed the strongest activity in inhibiting the arachidonic acid(AA)- and adenosine diphosphate(ADP)-induced platelet aggregation in vitro, with 3.8- and 7.0-fold more effectiveness than(S)-NBP, respectively. Furthermore, NOSH-NBP-5 could release moderate levels of NO and H2 S, which would be beneficial in improving cardiovascular and cerebral circulation. Moreover, NOSH-NBP-5 could release(S)-NBP when incubated with rat brain homogenate. In conclusion, these findings may provide new insights into the development of novel antiplatelet agents for the treatment of thrombosis-related ischemic stroke.
基金supported by the Natural Science Foundation of Anhui Province,China,No.1608085MH209(to YBW)New Medicine of University of Science and Techology of China,No.WK110000036(to YBW)
文摘A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic peripheral neuropathy. Therefore, this study investigated the effects of high glucose on proliferation, apoptosis, and 3-nitrotyrosine levels of Schwann cells treated with butylphthalide. In addition, we explored potential protective mechanisms of butylphthalide on peripheral nerves. Schwann cells were cultured in vitro with high glucose then stimulated with the peroxynitrite anion inhibitors uric acid and 3-n-butylphthalide for 48 hours. Cell Counting Kit-8 and flow cytometry were used to investigate the effects of uric acid and 3-n-butylphthalide on proliferation and apoptosis of Schwann cells exposed to a high glucose environment. Effects of uric acid and 3-n-butylphthalide on levels of 3-nitrotyrosine in Schwann cells were detected by enzyme-linked immunosorbent assay. The results indicated that Schwann cells cultured in high glucose showed decreased proliferation, but increased apoptosis and intracellular 3-nitrotyrosine levels. However, intervention with uric acid or 3-n-butylphthalide could increase proliferation of Schwann cells cultured in high glucose, and inhibited apoptosis and intracellular 3-nitrotyrosine levels. According to our data, 3-n-butylphthalide may inhibit cell nitrification and apoptosis, and promote cell proliferation, thereby reducing damage to Schwann cells caused by high glucose.
