Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Table 2

Pharmacotherapies targeting ferroptosis and necroptosis against cerebral ischemia or ischemic stroke. BCAS: bilateral common carotid artery stenosis.

Pharmacotherapy	Subject	Effects	References
Ferroptosis
DFO	MCAO rats	Decreases infarct volume	[24]
Statin	Acute ischemic stroke patients	Reduces cholesterol and enhances early reperfusion	[173, 175]
Vitamin B12	Lacunar stroke patients; MCAO model; one patient	Protects the BBB; improves neurological function; endothelial cell protection	[25, 176, 177]
Promethazine	HT1080 cell ferroptosis model; MCAO model	Suppresses ferroptosis; an excellent therapeutic effect; a good ability to permeate the BBB	[178]
Naotaifang	MCAO rats	Reduces ROS, MDA, and iron accumulation	[27]
Carvacrol	Ischemic stroke gerbils	Reduces lipid peroxidation levels and increases GPX4 expression	[26]
Ferroptosis; necroptosis
17-DMAG	MCAO mice; OGD-subjected bEnd.3 cells	Protects the BBB; inhibits HSP90 expression; suppresses inflammation	[186]
Necroptosis
Nec-1	BCAS mice	Inhibits RIP1 and RIP3 to reduce inflammation and improve cognitive function	[30]
Nec-1	MCAO rats	Decreases phosphorylated RIP1, RIP3, MLKL, and phosphorylated MLKL levels and the numbers of phosphorylated RIP1^+ neurons	[188]
Necrosulfonamide	MCAO mice	Reduces MLKL expression and infarct volume and improves neurological function	[189]
Dabrafenib	Focal ischemic brain injury model mice	Reduces TNF-α mRNA levels and infarct size	[31]
Infliximab	tMCAO rats	Reduces mitochondrial damage, cytoplasm transparency, and BBB permeability	[7]
Gsk872+RIP3 siRNA	MCAO mice; OGD-subjected HT-22 cells	Reduces RIP1, RIP3, MLKL, and phosphorylated MLKL levels to protect the neurological system	[171]
Ligustroflavone	MCAO rats	Reduces RIP3, MLKL, and phosphorylated MLKL levels to improve neurological function	[190]