The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Table 1

The main effects of artemisinin derivatives.

Name	Main functions		Mechanism	Adverse events
Arteether	Antiparasites	Plasmodium	Inducing iron-dependent free radicals’ generation	Anorexia; Cardiovascular symptom; Embryotoxicity; Immunosuppressive activity neurotoxicity
		Schistosoma	Reducing glycogen content and alkaline phosphatase activity
		Toxoplasma gondii	Unknown
	Anticancer	Tumor of the central nervous system	Inducing iron-dependent cell death
	Antifungi	Cryptococcus neoformans	Unknown
Artelinic acid	Antiparasites	Plasmodium	Unknown	Anemia; Embryotoxicity; Neurotoxicity; Nephrotoxicity; Reticulocytopenia; Vascular irritation
Artemether	Antiparasites	Plasmodium	Increasing production of reactive oxygen intermediates and reactive nitrogen intermediates	Anemia; Clastogenic potential; Distal tubular ectasia; Emesia; Endocrine disruption; Fetal growth retardation; Flattened epithelium in the kidney; Haemolytic anemia; Hemolysis; Hepatocellular hypertrophy; Hepatotoxicity; High liver weight; Immunosuppressive activity; Increases in hemoglobin levels; Meningeal inflammation; Neurotoxicity; Prolonged QT interval; Reduction in fetal body weight; Reduced oxytocin-induced contraction of uterine tissues; Slight damage to the proprius layer lamina of intestinal villi; Suppression of humoral responses; Transient focal vesicle degeneration of the liver
		Acanthamoeba castellanii	Be used as a hosphoglycerate dehydrogenase inhibitor
		Schistosoma	(1) Affecting both carbohydrate and protein metabolism of schistosomes; (2) By inhibition of GST and SOD enzymes, leading to increased schistosome susceptibility to oxidant attacks
		Toxoplasma gondii	By affecting the glucose-6-phosphatase of T. gondii, resulting in the energy metabolism of the parasite
	Anticancer	Pituitary macroadenoma	Unknown
		Glioma	Inhibiting the migration, invasiveness, expression of MMP-2/MMP-9 and p-Akt significantly while also promoting the apoptosis of tumor cells
	Anti-inflammation	Neuroinflammation	Inducing Nrf2 expression which results in the anti-inflammatory effect
	Antivirus	Cytomegalovirus	Unknown
Artemisinin	Antiparasites	Plasmodium	Generating highly reactive carbon-centered radicals via endoperoxide cleavage	Anemia; Anorexia; Cholestatic liver injury; Genital system injury; Hepatitis; Immunosuppressive activity; Neurotoxicity; Ptyalism
		Schistosoma	Unknown
		Toxoplasma gondii	(1) Inhibiting the intracellular growth of T. gondii in vitro by imposing oxidative stress within the cells; (2) Perturbing calcium homeostasis in T. gondii
		Trypanosoma	Inhibiting calcium-dependent ATPase activity in T. cruzi membranes
	Anticancer	Brain tumor	(1) Bringing about reactive oxygen species-mediated action; (2) Inducing iron-dependent cell death
	Anti-inflammation	Alzheimer’s disease	Suppressing NF-κB activity and NALP3 inflammasome activation
	Antifungi	C. neoformans	Unknown
		C. albicans	Unknown
	Antivirus	Cytomegalovirus	Modulating cell cycle through CDKs and pRb
		Herpes virus	Unknown
	Others	Schizophrenia	Reducing levels of antibodies to gliadin
		Neurite outgrowth	Activating ERK and p38 MAPK signaling pathways
		Vascular	(1) Inhibiting VSMC migration through down-regulation of ERK1/2 and MMP9 phosphorylation; (2) Inhibiting the inflammation of VSMCs induced by TNF-α through ROS-mediated NF-κB signal pathway
Artesunate	Antiparasites	Plasmodium	(1) Inhibiting the activity of the cytochrome oxidase; (2) Increasing oxidant stress on the infected red cells	Anaphylaxis; Anemia; Cardiovascular system; Contragestational action; Haemolysis; Immunosuppressive activity; Neurotoxicity
		Echinococcus	Unknown
		Heterophyid	Unknown
		Schistosoma	Reducing expression of schistosome thioredoxin glutathione reductase and cytochrome c peroxidase
		Toxoplasma gondii	Distorting in tachyzoites’ shape, peeling, erosions and discontinuity in areas of surface membrane
		Trypanosoma	Unknown
	Anticancer	Glioma	Inducing oxidative DNA lesions and DNA double-strand breaks
		Neuroblastoma	Inducing apoptosis and reactive oxygen species in neuroblastoma cells
		Schwannoma	Inducing cell death dependent on necroptosis
		Neurofibromatosis	Binding to and degrading translationally controlled tumor protein
		Growth hormone adenoma	Inhibiting proliferation and inducing apoptosis by caspase-dependent pathways
	Anti-inflammation	Neuroinflammatory	Influencing NF-kB, p38 MAPK and Nrf2/ARE-dependent signal pathway
	Antivirus	Cytomegalovirus	Interfering with the NF-κB pathway by targeting RelA/p65
		Ebola virus	Unknown
		Epstein-Barr virus	Blocking viral immediate early protein synthesis
		Herpes virus	Unknown
		Polyomavirus	Leading to cytostatic effects on the host cell
	Others	Subarachnoid hemorrhage	Protecting BBB via S1P1/PI3K pathway after subarachnoid hemorrhage
		Vascular	(1) Inhibiting VSMCs proliferation by disturbing DNA replication, inducing cell apoptosis and blocking cell cycle in G0/G1 phase; (2) Inducing apoptosis of endothelial cells via an iron/ROS-dependent p38 MAPK-mitochondrial pathway; (3) Inhibiting NF-κB nuclear translocation and the subsequent expression of ICAM-1
Dihydroartemisinin	Antiparasites	Plasmodium	(1) Generating highly reactive carbon-centered radicals via endoperoxide cleavage; (2) Causing the pigment of P. berghei to clump	Contragestational effects; Embryotoxicity; Erythroid cell differentiation; Hemolysis; Immunosuppressive activity; Neurotoxicity; Suppression of humoral responses
		Naegleria fowleri	Unknown
		Schistosoma	Causing damage to the genital system of worms
		Toxoplasma gondii	Unknown
	Anticancer	Neuroblastoma	Damaging mitochondrial cristae and endoplasmic reticulum
		Glioma	(1) Inhibiting the Raf/ERK/MEK, ADAM17, PI3K/AKT pathways and activating caspase-3; (2) Increasing the reactive oxygen species and inhibiting hypoxia inducible factor-1α activation
	Others	Neurite outgrowth	Activating ERK and p38 MAPK signaling pathways
		Vascular	(1) Inhibiting VEGF-induced EC migration via a p38 MAPK-independent pathway; (2) Repressing the NF-κB pathway
Artemiside	Antiparasites	Plasmodium	Unknown	Unknown
		Toxoplasma gondii	Unknown
Artemisitene	Antiparasites	Plasmodium	Unknown	Unknown
		Trypanosoma	Unknown
	Anticancer	Tumor of the central nervous system	Inducing iron-dependent cell death
Artemisone	Antiparasites	Plasmodium	Resulting in antimalarial activities by the Fe2+-mediated decomposition, PfATP6 binding	Embryotoxicity; Cardiac ventricular septal defects; Vascular variation
		Toxoplasma gondii	Unknown
Artefenomel (OZ439)	Antiparasites	Plasmodium	Activating hemoglobin degradation	Unknown
Arterolane (OZ277)	Antiparasites	Plasmodium	Activating hemoglobin degradation	Embryotoxicity
		Schistosoma	Unknown
Arteanuin B	Anticancer	Tumor of the central nervous system	Inducing iron-dependent cell death	Unknown
	Others	Vascular	Inhibiting immune mediators of angiogenesis
SM735	Anti-inflammation	Immunosuppressive activity	Inhibiting the proliferation of splenocytes, proinflammatory cytokine production, T cell-mediated delayed-type hypersensitivity (DTH) and B-cell-mediated QHS reactions	Unknown
SM905	Anti-inflammation	Immunosuppressive activity	Inhibiting T cell activation, NO and proinflammatory cytokine production by suppressing and Ras activation, MAPK and NF-kappaB pathways	Unknown
SM933	Anti-inflammation	Autoimmune encephalomyelitis	Involving the NF-kB and the Rig-G/JAB1 signaling pathways	Unknown
SM934	Anti-inflammation	Autoimmune encephalomyelitis; Immunosuppressive activity	Inducing Treg differentiation and expansion; Inhibiting T cell activation	Unknown
Artemisinin dimer 1	Anticancer	Tumor of the central nervous system	Inducing iron-dependent cell death	Unknown
Artemisinin dimer 2	Anticancer	Tumor of the central nervous system	Inducing iron-dependent cell death	Unknown
Artemisinin dimer hemisuccinate	Anticancer	Tumor of the central nervous system	Inducing iron-dependent cell death	Unknown
Artesunate derivative	Anticancer	Tumor of the central nervous system	Inducing iron-dependent cell death	Unknown
CPM-1	Antiparasites	Plasmodium	Unknown	Unknown
11-Azaartemisinins	Antiparasites	Plasmodium	Unknown	Unknown
10-Aminoethylether derivatives of artemisinin	Antiparasites	Plasmodium	Unknown	Unknown
Artefanilide	Antivirus	Cytomegalovirus	Unknown	Unknown