Oxidative Medicine and Cellular Longevity

Review Article

Neuroprotection of Catalpol for Experimental Acute Focal Ischemic Stroke: Preclinical Evidence and Possible Mechanisms of Antioxidation, Anti-Inflammation, and Antiapoptosis

Table 3

Characteristics of mechanism studies of catalpol on experimental ischemic stroke.


Study (years)	Model	Method of administration (experimental group versus control group)	Observations	Possible mechanisms

Jia et al. [14]	MCAO/1 h in Wistar rats	Catalpol versus saline	Increased β-endorphin levels and the effects were reversed by GLP-1R orthosteric antagonist	GLP-1R/β-endorphin pathway
Jia et al. [14]	MCAO/1 h in Wistar rats	Catalpol versus saline	Reduced IV and improved NFS	GLP-1R/β-endorphin pathway
Wan et al. [15]	Permanent MCAO in SD rats	Catalpol versus normal saline	Increased synapse quantity upregulated GAP43 expression	Promotion of survival, reparation, and regeneration of neural cells
Wan et al. [15]	Permanent MCAO in SD rats	Catalpol versus normal saline	Improved NFS
Zhu et al. [17]	Permanent MCAO in Kunming mice	Catalpol versus normal saline	Increased EPO and VEGF expression	Enhancement of angiogenesis
Zhu et al. [17]	Permanent MCAO in Kunming mice	Catalpol versus normal saline	Improved NFS, increased VWF and PCNA co-localization points, improved the vascular pattern of the cerebral cortex surface, and reduced BCEC edema	Enhancement of angiogenesis
Wang [18]	Permanent MCAO in SD rats	Catalpol versus normal saline	Upregulated the levels of VEGF, JAK2, and STAT3 Reduced IV	Enhancement of angiogenesis
Zhang et al. [20]	Permanent MCAO in Kunming mice	Catalpol versus no treatment	Increased SOD activity and decreased MDA and NO concentration Improved NFS	Reduction of oxidative reactions
Min et al. [21]	MCAO/2 h in SD rats	Catalpol versus dimethyl sulfoxide	Increased GSH-PX activity, decreasing MDA concentration Reduced IV and improved NFS	Reduction of oxidative reactions
Min [22]	MCAO/2 h in SD rats	Catalpol versus no treatment	Increased GSH-PX, SOD, and catalase activity, increased NOX2 expression, decreased MDA concentration Increased bcl-2 expression and decreased cleaved caspase-3 and Bax expression Reduced IV and improved NFS Reduced apoptotic cells	Reduction of oxidative reactions Inhibition of apoptosis
Liu 2011 [23]	MCAO/2 h in SD rats	Catalpol versus edible oil	Increased SOD activity, decreased MDA concentration Decreased IL10 expression Increased bcl-2 expression and decreased Bax expression Increased the expression of NGF, BDNF, VEGF, bFGF, TrKA, PI3K, and AKt, increased the mRNA levels of NGF, BDNF, TrKA, and AKt, decreased CDNF expression and PI3K mRNA level Decreased lactic acid content, increased pyruvic acid content, and improved Na⁺, K⁺-ATPase and Ca²⁺, Mg²⁺-ATPase activities Improved NFS Increased neuron number and nissl body number, improved cerebral cortex ultrastructure	Reduction of oxidative reactions Repression of inflammatory reactions Inhibition of apoptosis Promotion of survival, reparation, and regeneration of neural cells Relief of energy exhaustion
Wan et al. 2012 [24]	Permanent MCAO in SD rats	Catalpol versus normal saline	Increased dendritic branches and spine density and increased P38 expression Improved NFS	Promotion of survival, reparation, and regeneration of neural cells
Wang [25]	MCAO/2 h in SD rats	Catalpol versus normal saline	Increased LC3 expression Improved neurovascular unit structure Reduced IV and improved NFS	Repression of autophagy
Liu et al. 2011 [27]	Permanent MCAO in SD rats	Catalpol versus distilled water	Decreased lactic acid content, increased pyruvic acid content, and improved Na⁺, K⁺-ATPase and Ca²⁺, Mg²⁺-ATPase activities Improved NFS	Relief of energy exhaustion
Liu et al. 2011 [28]	Permanent MCAO in SD rats	Catalpol versus edible oil	Increased neuron number Increased the expression and mRNA levels of NGF and BDNF Improved NFS	Promotion of survival, reparation, and regeneration of neural cells
Wan et al. 2012 [31]	Permanent MCAO in SD rats	Catalpol versus normal saline	Increased dendritic branches and spine density Increased the expression of EPO, VEGF, STAT3, GAP-43, P38, BDNF, and Trk B Improved NFS	Enhancement of angiogenesis Promotion of survival, reparation, and regeneration of neural cells
Zhou [32]	Permanent MCAO in SD rats	Catalpol versus normal saline	Increased Ang-1 expression Improved NFS	Enhancement of angiogenesis
Wan et al. 2013 [33]	Permanent MCAO in SD rats	Catalpol versus normal saline	Increased remodeling and sprouting of CST axonal Increased the expression of GAP-43 Reduced IV and improved NFS	Enhancement of angiogenesis Promotion of survival, reparation, and regeneration of neural cells
Tan et al. [34]	Permanent MCAO in SD rats	Catalpol versus normal saline	Improved cell morphology and increased the number of neuron, glial cells, and vessel length Improved NFS	Enhancement of angiogenesis Promotion of survival, reparation, and regeneration of neural cells
Zhang et al. [35]	Permanent MCAO in SD rats	Catalpol versus edible oil and normal saline	Improved cell morphology and increased myelin sheath and increased MBP expression Improved NFS	Promotion of survival, reparation, and regeneration of neural cells
Qin [36]	Permanent MCAO in SD rats	Catalpol versus normal saline	Promote the proliferation and differentiation of neural stem cells and the survey of neuron Increased ratio of Bcl-2/Bax, reduced the expression of caspase-9 and caspase-3 Improved NFS	Inhibition of apoptosis
Wan et al. [38]	Permanent MCAO in SD rats	Catalpol versus no treatment	Increased VWF-PCNA colocalization Increased the expression of EPO, EPOR, pJAK2, pSTAT3, VEGF, and VEGF mRNA Improved NFS	Enhancement of angiogenesis

AKt: serine/threonine kinase; Ang-1: angiopoietin 1; BCEC: brain capillary endothelial cells; bcl-2: B-cell lymphoma-2; BDNF: brain-derived neurotrophic factor; bFGF: basic fibroblast growth factor; CDNF: cerebral dopamine neurotrophic factor; CST: corticospinal tract; EPO: erythroprotein; EPOR: erythroprotein receptor; GAP-43: growth-associated protein 43; GLP-1R: glucagon-like peptide-1 receptor; GSH-PX: glutathione peroxidase; HO-1: heme oxygenase-1; IL: interleukin; IV: infarct volume; JAK2: janus kinase 2; MCAO: middle carotid artery occlusion; MDA: malondialdehyde; NFS: neurological function score; NGF: nerve growth factor; PCNA: proliferating cell nuclear antigen; PI3K: phosphoinositide-3 kinase; pJAK2: phosphorylated janus kinase 2; pSTAT3: phosphorylated signal transducer and activator of transcription-3; SD: Sprague Dawley; SOD: superoxide dismutase; STAT3: the Stroke Therapy Academic Industry Roundtable; TrKA: tyrosine kinase receptor A; TrKB: tyrosine kinase receptor B; VEGF: vascular endothelial growth factor; VWF: Von Willebrand factor.