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CNS & Neurological Disorders - Drug Targets

Author(s): Fangfang Zhao and Yumin Luo*

DOI: 10.2174/1871527321666211221160922

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Potential Protective Effect of Dl-3-n-butylphthalide on Chronic Cerebral Ischemia Brain Injury

Page: [734 - 737] Pages: 4

  • * (Excluding Mailing and Handling)

Abstract

Chronic cerebral ischemia is one of the common ischemic cerebrovascular diseases. Chronic cerebral ischemia can lead to brain dysfunction, and its pathophysiological mechanism involves inflammation, blood-brain barrier destruction, oxidative stress, and other factors. As it is difficult to detect, it is easily overlooked, and it is often only observed following the onset of cognitive dysfunction. At present, there are only a few drugs for its treatment. Dl-3-n-butylphthalide (NBP), a compound extracted from celery seed, may play an important role in protecting against brain damage caused by chronic cerebral ischemia. Therefore, here, we have paid attention to the prevention and treatment of chronic cerebral ischemia with NBP.

Keywords: Chronic cerebral ischemia, NBP, brain damage, inflammation, blood-brain barrier destruction, oxidative stress.

Graphical Abstract

[1]
Belayev L, Obenaus A, Mukherjee PK, et al. Blocking pro-inflammatory platelet-activating factor receptors and activating cell survival pathways: A novel therapeutic strategy in experimental ischemic stroke. Brain Circ 2020; 6(4): 260-8.
[http://dx.doi.org/10.4103/bc.bc_36_20] [PMID: 33506149]
[2]
Sun Y, Zhao Z, Li Q, et al. Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats. J Int Med Res 2020; 48(7): 300060520936177.
[http://dx.doi.org/10.1177/0300060520936177] [PMID: 32644834]
[3]
Lee KM, Bang J, Kim BY, et al. Fructus mume alleviates chronic cerebral hypoperfusion-induced white matter and hippocampal damage via inhibition of inflammation and downregulation of TLR4 and p38 MAPK signaling. BMC Complement Altern Med 2015; 15: 125.
[http://dx.doi.org/10.1186/s12906-015-0652-1] [PMID: 25898017]
[4]
Iglesias J, Morales L, Barreto GE. Metabolic and inflammatory adaptation of reactive astrocytes: Role of PPARs. Mol Neurobiol 2017; 54(4): 2518-38.
[http://dx.doi.org/10.1007/s12035-016-9833-2] [PMID: 26984740]
[5]
Kakae M, Tobori S, Morishima M, Nagayasu K, Shirakawa H, Kaneko S. Depletion of microglia ameliorates white matter injury and cognitive impairment in a mouse chronic cerebral hypoperfusion model. Biochem Biophys Res Commun 2019; 514(4): 1040-4.
[http://dx.doi.org/10.1016/j.bbrc.2019.05.055] [PMID: 31097227]
[6]
Washida K, Hattori Y, Ihara M. Animal models of chronic cerebral hypoperfusion: From mouse to primate. Int J Mol Sci 2019; 20(24): E6176.
[http://dx.doi.org/10.3390/ijms20246176] [PMID: 31817864]
[7]
Bjerke M, Zetterberg H, Edman Å, Blennow K, Wallin A, Andreasson U. Cerebrospinal fluid matrix metalloproteinases and tissue inhibitor of metalloproteinases in combination with subcortical and cortical biomarkers in vascular dementia and Alzheimer’s disease. J Alzheimers Dis 2011; 27(3): 665-76.
[http://dx.doi.org/10.3233/JAD-2011-110566] [PMID: 21860087]
[8]
Cheng P, Ren Y, Bai S, et al. Chronic cerebral ischemia induces downregulation of A1 adenosine receptors during white matter damage in adult mice. Cell Mol Neurobiol 2015; 35(8): 1149-56.
[http://dx.doi.org/10.1007/s10571-015-0208-4] [PMID: 25982512]
[9]
Miyanohara J, Kakae M, Nagayasu K, et al. TRPM2 channel aggravates CNS inflammation and cognitive impairment via activation of microglia in chronic cerebral hypoperfusion. J Neurosci 2018; 38(14): 3520-33.
[http://dx.doi.org/10.1523/JNEUROSCI.2451-17.2018] [PMID: 29507145]
[10]
Li W, Pan R, Qi Z, Liu KJ. Current progress in searching for clinically useful biomarkers of blood-brain barrier damage following cerebral ischemia. Brain Circ 2018; 4(4): 145-52.
[http://dx.doi.org/10.4103/bc.bc_11_18] [PMID: 30693340]
[11]
Ueno M, Tomimoto H, Akiguchi I, Wakita H, Sakamoto H. Blood-brain barrier disruption in white matter lesions in a rat model of chronic cerebral hypoperfusion. J Cereb Blood Flow Metab 2002; 22(1): 97-104.
[http://dx.doi.org/10.1097/00004647-200201000-00012] [PMID: 11807399]
[12]
Holland PR, Searcy JL, Salvadores N, et al. Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease. J Cereb Blood Flow Metab 2015; 35(6): 1005-14.
[http://dx.doi.org/10.1038/jcbfm.2015.12] [PMID: 25669904]
[13]
Candelario-Jalil E, Thompson J, Taheri S, et al. Matrix metalloproteinases are associated with increased blood-brain barrier opening in vascular cognitive impairment. Stroke 2011; 42(5): 1345-50.
[http://dx.doi.org/10.1161/STROKEAHA.110.600825] [PMID: 21454822]
[14]
Behl T, Kaur G, Sehgal A, et al. Multifaceted role of matrix metalloproteinases in neurodegenerative diseases: Pathophysiological and therapeutic perspectives. Int J Mol Sci 2021; 22(3): 1413.
[http://dx.doi.org/10.3390/ijms22031413] [PMID: 33573368]
[15]
Kim GW, Gasche Y, Grzeschik S, Copin JC, Maier CM, Chan PH. Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: Role of matrix metalloproteinase-9 in early blood-brain barrier disruption? J Neurosci 2003; 23(25): 8733-42.
[http://dx.doi.org/10.1523/JNEUROSCI.23-25-08733.2003] [PMID: 14507973]
[16]
Li J, Liu Y, Zhang X, et al. Dl-3-N-butylphthalide alleviates the blood-brain barrier permeability of focal cerebral ischemia reperfusion in mice. Neuroscience 2019; 413: 99-107.
[http://dx.doi.org/10.1016/j.neuroscience.2019.06.020] [PMID: 31247236]
[17]
Han QY, Zhang H, Zhang X, et al. dl-3-n-butylphthalide preserves white matter integrity and alleviates cognitive impairment in mice with chronic cerebral hypoperfusion. CNS Neurosci Ther 2019; 25(9): 1042-53.
[http://dx.doi.org/10.1111/cns.13189] [PMID: 31334611]
[18]
Hu J, Wen Q, Wu Y, Li B, Gao P. The effect of butylphthalide on the brain edema, blood-brain barrier of rats after focal cerebral infarction and the expression of Rho A. Cell Biochem Biophys 2014; 69(2): 363-8.
[http://dx.doi.org/10.1007/s12013-013-9808-0] [PMID: 24442989]
[19]
Liu CY, Zhao ZH, Chen ZT, et al. DL-3-n-butylphthalide protects endothelial cells against advanced glycation end product-induced injury by attenuating oxidative stress and inflammation responses. Exp Ther Med 2017; 14(3): 2241-8.
[http://dx.doi.org/10.3892/etm.2017.4784] [PMID: 28962149]
[20]
Ye ZY, Xing HY, Wang B, Liu M, Lv PY. DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins. Chin Med J (Engl) 2019; 132(11): 1344-53.
[http://dx.doi.org/10.1097/CM9.0000000000000232] [PMID: 30939485]
[21]
Zhao CY, Lei H, Zhang Y, et al. L-3-n-Butylphthalide attenuates neuroinflammatory responses by downregulating JNK activation and upregulating heme oxygenase-1 in lipopolysaccharide-treated mice. J Asian Nat Prod Res 2016; 18(3): 289-302.
[http://dx.doi.org/10.1080/10286020.2015.1099524] [PMID: 26675131]
[22]
Wang HM, Zhang T, Huang JK, Sun XJ. 3-N-butylphthalide (NBP) attenuates the amyloid-β-induced inflammatory responses in cultured astrocytes via the nuclear factor-κB signaling pathway. Cell Physiol Biochem 2013; 32(1): 235-42.
[http://dx.doi.org/10.1159/000350139] [PMID: 23899885]
[23]
Zhao W, Luo C, Wang J, et al. 3-N-butylphthalide improves neuronal morphology after chronic cerebral ischemia. Neural Regen Res 2014; 9(7): 719-26.
[http://dx.doi.org/10.4103/1673-5374.131576] [PMID: 25206879]
[24]
Lei H, Zhang Y, Huang L, et al. L-3-n-butylphthalide regulates proliferation, migration, and differentiation of neural stem cell in vitro and promotes neurogenesis in APP/PS1 mouse model by regulating BDNF/TrkB/CREB/Akt pathway. Neurotox Res 2018; 34(3): 477-88.
[http://dx.doi.org/10.1007/s12640-018-9905-3] [PMID: 29728920]
[25]
Zhang L, Lü L, Chan WM, Huang Y, Wai MS, Yew DT. Effects of DL-3-n-butylphthalide on vascular dementia and angiogenesis. Neurochem Res 2012; 37(5): 911-9.
[http://dx.doi.org/10.1007/s11064-011-0663-3] [PMID: 22246225]
[26]
Liebner S, Dijkhuizen RM, Reiss Y, Plate KH, Agalliu D, Constantin G. Functional morphology of the blood-brain barrier in health and disease. Acta Neuropathol 2018; 135(3): 311-36.
[http://dx.doi.org/10.1007/s00401-018-1815-1] [PMID: 29411111]
[27]
Yan Y, Lou J, Bai H, et al. Expression of neuroglobin in rats with cerebral infarction and the intervention effect of butylphthalide. J Apoplexy and Nervous Diseases 2015; 32(5): 430-3.
[28]
Li L, Zhang B, Tao Y, et al. DL-3-n-butylphthalide protects endothelial cells against oxidative/nitrosative stress, mitochondrial damage and subsequent cell death after oxygen glucose deprivation in vitro. Brain Res 2009; 1290: 91-101.
[http://dx.doi.org/10.1016/j.brainres.2009.07.020] [PMID: 19616517]
[29]
Ye J, Zhai L, Zhang S, et al. DL-3-n-butylphthalide inhibits platelet activation via inhibition of cPLA2-mediated TXA2 synthesis and phosphodiesterase. Platelets 2015; 26(8): 736-44.
[http://dx.doi.org/10.3109/09537104.2014.989826] [PMID: 25734213]
[30]
Kong S, Li Q, Yang J, He L. The effect of butylphthalide on the expression of NGF and BDNF in ischemic brain tissue of rats. J Sichuan Univ (Med Ed) 2007; 38(3): 400-7.
[31]
Li J, Li Y, Ogle M, et al. DL-3-n-butylphthalide prevents neuronal cell death after focal cerebral ischemia in mice via the JNK pathway. Brain Res 2010; 1359: 216-26.
[http://dx.doi.org/10.1016/j.brainres.2010.08.061] [PMID: 20800583]