Table 2.

Summarized effects and mechanisms of NBP on different targets related to ischemic stroke in in vivo and in vitro studies.

Model	Type	Tissue sites	Effects	Mechanisms	RF
Endothelin-1-induced focal cerebral ischemia in rats	In vivo	Focal cerebral ischemia injury	↑ number and length of crossing CST fibers ↑ PSD95 and VGlut-1 levels ↑ number of BrdU+/DCX+ cells ↓ rho-A+, ROCK+, Nogo-A+ and Nogo-R+ cells ↑ behavioral performance	↑ axonal growth ↑ neurogenesis	[53]
p MCAO in rats	In vivo	Cerebral ischemia infarction	↓ glucose and citric acid levels ↑ ATP, ADP, AMP, and GMP metabolism ↑ glutamate, glutamine, aspartate, and N-acetylaspartate levels ↑ glutathione, ascorbic acid, and taurine levels ↓ number of sodium ions ↑ number of potassium ions	↑ ATP metabolism ↑ antioxidant level Maintain sodium-potassium ion balance	[52]
Endothelin-1-induced focal cerebral ischemia in rats	In vivo	Stroke-induced white matter injury	↑ differentiation and maturation of OPCs ↑ length of CST fibers into the denervated hemispheres	↑ Remyelination ↑ BDNF level ↓ NogoA level	[57]
OGD in cortical neurons	In vitro	Ischemic stroke	↑ number of primary and secondary dendrites and of dendritic tips	Regulate dendritic branching ↓ PI3K/AKT Signaling	[54]
p MCAO in mice	In vivo	Cerebral infarction	↓ neurologic function deficits ↓ infarction volume ↓ BBB permeability ↓ MMP-9 expression ↑ Claudin-5 expression	↑ VEGF and GFAP expression ↑ ultrastructure in capillary Endothelial cells of BBBs ↑ Nrf-2/HO-1 signaling pathway	[47]
MCAO in rats	In vivo	Cerebral ischemia	↑ body weight ↓ infarct volume ↑ neurobehavioral outcomes ↑ number of CD31+ microvessels ↑ number of CD31+/BrdU+ proliferating endothelial cells ↑ functional Vascular density ↑ VEGF level ↑ angiopoietin-1 level	↑ angiogenesis ↑ sonic hedgehog expression	[55]
MCAO in mice Photothrombosis-induced permanent cerebral ischemia in mice	In vivo	Ischemic stroke	↓ ICAM-1 level ↓ PAR-1 level ↓ brain infiltration of myeloid cells Preserve BBB integrity ↑ cerebral blood flow	↓ neurovascular inflammation	[48]
t MCAO in mice	In vivo	Cerebral I/R injury	↓ infarct volume ↓ neurological deficit ↓ cerebral edema ↓ BBB permeability	↑ blood flow ↓ BBB dysfunction	[49]
ADP, thrombin, U46619, AA, and collagen-induced platelet activation in human	In vivo	Arterial thrombotic diseases heart attack and stroke	↓ human platelet Aggregation and ATP release PAC-1 binding ↓ TXA2 synthesis ↓ intracellular calcium mobilization	↓ cPLA2-mediated TXA2 synthesis ↓ PDE level ↑ 3,5-cyclic adenosine monophosphate level	[51]
BCCAO in rats	In vivo	Chronic cerebral hypoperfusion	↑ CBF recovery ↑ hemodynamic compensation ↓ astrogliosis ↓ cell apoptosis Protect hippocampal neurons	↑ hemodynamics ↑ CBF recovery ↑ cognitive function	[50]
MCAO in mice	In vivo	Ischemic stroke	↑ functional recovery ↑ number of RECA-1 positive vessels ↑ occludin expression ↑ HIF-1α expression ↑ VEGF, notch, and DLL-4 expression	↑ white matter integrity, ↑ occludin expression ↑ HIF-1α/VEGF/notch/Dll4 expression	[64]
OGD in SV40-transformed aortic rat endothelial cell line	In vitro	Ischemic injury	↓ endothelial cells injury ↑ PGC-1α expression ↑ vascular proliferation	Maintain the endothelial PGC-1α expression via regulating eNOS activity	[56]

RF: reference; other abbreviations as shown in the literature. (↓): downregulation or inhibition; (↑): upregulation or activation.