Hydroxysafflor Yellow A: A Promising Therapeutic Agent for a Broad Spectrum of Diseases

Table 2

Summary about the neuroprotection of HYSA.

Effects	Model	Details	Ref.
Cerebral ischemia	Rat fetal cortical cells stimulated by OGD.	Preventing cell death and LDH release.	[28]
	Rat fetal cortical cells stimulated by glutamate and NaCN	Preventing cell death and release of LDH and NO.	[29]
	MCAO rats	Reducing neurological deficit scores, infarct area, edema extend, cell apoptosis and expressions of Bax, Caspase-3, ICAM-1, IL-1β, TNF-α and NF-κB, improving glucose metabolism and increasing expressions of GFAP, NGF and Bcl-2.	[28–30]
	MCAO rats	Decreasing infarct sizes, neurological deficit scores and cerebrovascular permeability.	[6]
	Coronary artery and basilar artery rings of dogs	Having a stronger effect on cerebrovascular vasodilatation than on cardiovascular vasodilatation.	[6]
	MCAO rats	Reducing neurological deficit scores, suppressing thrombin generation, suppressing thrombin generation, NF-κB p65 nuclear translation, p65 binding activity, elevating ICAM-1 mRNA and protein levels and neutrophils infiltration and decreasing Ang II.	[31, 32]
	MCAO rats	Decreasing apoptotic cell number, increasing Bcl-2/Bax proportion, and elevating levels of Akt and GSK-3β phosphorylation in the penumbral cortex.	[33]
	MCAO rats	Decreasing infarct volume, and increasing BDNF and decreasing TLR4 expression, phosphorylation of NF-κB p65, ERK1/2, JNK and p38 and secretion of TNF-α, IL-1β and NO.	[34]
	MCAO rats	Reducing infarct volume, improving neurological scores and activating Akt-autophagy.	[35]
	MCAO rats	Reducing infarct volume, neurological deficit scores, inhibiting expressions of TNF-α, IL-1 and IL-6, and p65 translocation and binding activity, up-regulating expression of IL-10 and restoring the metabolism pathways.	[36]
	MCAO rats	Decreasing BBB permeability, improving tight junction, attenuating expressions of occludin, claudin-5 and ZO-1 and regulating the tight junction pathway.	[37, 38]
	MCAO rats	Decreasing infarct volume, BBB permeability, brain edema, production of carbonyl and expressions of 12/15-LOX and 15-HETE and elevating nitrotyrosine.	[39]
	MCAO rats	Reducing infarct volume, BBB permeability, brain edema, expression of iNOS and level of NO end product and 3-NT and improving neurological scores.	[40]
	Bovine serum albumin and primary cortical neurons induced by authentic peroxynitrite	Alleviating tyrosine nitration.	[40]
	OGD-induced PC12 cells	Promoting cell viability, reducing MDA, apoptotic cells and expressions of Bax, Caspase-3 and cyto c and increasing Bcl-2 expression and SOD activity.	[41]
	LPS-activited co-existance system for microglia and neurons	Suppressing TLR4 expression, down-regulating MyD88, NF-κB, JNK, ERK1/2 and p38 and release of TNF-α, IL-β and NO and increasing BDNF expression.	[42]
	Rat cortical neurons subjected to NMDA	Reducing cell apoptosis, expressions of Bax and NR2B-containing NMDA receptors and increasing Bcl-2 expression. Decreasing apoptotic cell number, increasing BCl2/Bax proportion, elevating levels of Akt and GSK-3β phosphorylation in the penumbral cortex.	[43]
	Mouse hippocampal slices	Inhibiting EPCs, postsynaptic NMDAR activity and pre-synaptic glutamate transmitter release, NMDAR-mediated OGD-evoked membrane depolarization current and NMDAR-dependent ischemic LTP induced by OGD.	[44]
	Mouse hippocampal neurons	Inhibiting NMDA-mediated and NMDAR- induced intracellular Ca^2+ influx, NMDAR-induced cell apoptosis and necrotic cell deaths, and NMDA-induced mitochondrial injury.	[44]
	MCAO rats	Inhibiting overloaded Ca^2+ and scavenge capability of free radicals, increasing the membrane fluidity and activities of respiratory enzymes and decreasing edema degree and membrane phospholipid decomposability in the cortex mitochondria.	[45]
	MCAO rats	Increasing latency time on rotarod and alteration behavior in Y-maze, levels of GSH and catalase, and reducing neurological deficit scores, levels of MDA and TNF-β, and infarct volume.	[46]
	Mitochondria isolated from rat brains suffered from Ca^2+ and H2O2	Alleviating swelling, reducing ROS generation, improving mitochondrial energy metabolism and increasing ATP level and the respiratory control ratio.	[47]
Dementia	VD rats by 2-VO	Reducing escape latency, prolonged time spent in the platform quadrant and swimming distance in the water maze, and increasing LTP and finally ameliorating learning and memory, up-regulating expressions of VEGF-A, NR1, BDNF and NMDAR in the hippocampal.	[48, 49]
	AD rats induced by Hcy	Shortening escape latency, reducing the number to cross the hidden platform and time spent in the target quadrant, attenuating A, A and PS1 protein levels, rescuing cell apoptosis and increasing LTP.	[50]
	A-induced AD mice	Decreasing memory deficits and expressions of Iba-1, GFAP, IL-1, TNF-α and iNOS, increasing expressions of IL-4 and IL-10 and suppressing activation of microglia and astrocytes in the hippocampi.	[51]
	A-induced BV-2 cells	Increasing cell viability, reducing mRNA levels of IL-1β, TNF-α, COX-2 and iNOS and protein expressions of COX-2, TNF-α and iNOS and up-regulating IL-4, IL-10 and phosphorylation protein expressions of JAK2 and STAT3.	[52]
	Neurons and SH-SY5Y cells inhibited by conditioned meadium of A-induced BV-2 cells	Promoting cell viability and inhibiting cell apoptosis.	[52]
	A-induced PC12 cells	Increasing cell viability, stabilizing mitochondrial function and reducing LDH, intracellular ROS, MDA and neuronal apoptosis.	[53]
TBI	TBI rats	Reducing contusion volume, MDA and GSSG in the brain, plasma PAI-1 activity and MMP-9 expression in the hippocampus, and increasing activities of SOD, CAT, GSH, t-PA and mitochondrial ATPase and the GSH/GSSG ratio.	[54, 55]
Other nervous system diseases	LE-induced brain injury in rats	Decreasing the neurological scores, cell apoptosis in RVLM, up-regulating eNOS expression in both of mRNA and protein levels of RVLM and reducing HRV.	[56]
	Spinal cord compression injury rats	Decreasing neurological deficit score, MDA, MPO, NO, TNF-α, IL-6, iNOS, COX-2, activities of NF-κB and Caspase-3, water content in spinal cord and permeability in BSCB and increasing SOD activity.	[57]