cerebral ischemia

Minocycline hydrochloride (Minocycline HCl) is a tetracycline antibiotic with excellent absorption and tissue penetration that is used for several bacterial infections as well as treatment of acne. Minocycline hydrochloride can cause both an acute hepatitis-like syndrome occurring within 1 to 3 months of starting therapy or a more insidious chronic hepatitis with autoimmune features typically after long-term treatment.

Orotirelin(CG 3509), a thyrotropin-releasing hormone analog, reversed pentobarbital-induced sleep time.Orotirelin may be beneficial in animals with focal cerebral ischemia.

Citicoline sodium (CDP-choline) is an endogenous intermediate in the synthesis of phosphatidylcholine. It also serves as a choline donor in the biosynthesis of the neurotransmitter acetylcholine. Citicoline sodium demonstrates protective effects in cerebral ischemia, traumatic brain injury, and memory disorders. Exogenous administration of citicoline to rodents (500 mg kg i.p. immediately after ischemia and at 3-h reperfusion) has been shown to stimulate the synthesis of phosphatidylcholine, sphingomyelin, and cardiolipin and to attenuate the release of arachidonic acid and the accumulation of ceramide.

Sesamin is a selective delta 5 desaturase inhibitor in the biosynthesis of polyunsaturated fatty acids and is a lignan abundantly present in sesame oil. It has potent neuroprotective effects against cerebral ischemia.

Butylphthalide (3-Butylphthalide) is an anti-cerebral-ischemia drug; first isolated from the seeds of Apium graveolens Linn.

Musk ketone can induce the growth repression and the apoptosis of cancer cells. Musk ketone increases activity of glutathione S-transferase and thus may prove to be useful cancer chemoprotectant.

BAPTA is a neuroprotective agent in cerebral ischemia, acting as an intercellular Ca2+ chelator.

Dihydrocapsaicin (CCRIS1589) is isolated from Capsicum fruit. Capsaicin is the primary active component of the heat and pain-eliciting lipid soluble fraction of the Capsicum pepper. Like capsaicin, dihydrocapsaicin is an irritant. Capsaicin is found in natural hot pepper extracts along with a number of impurities, including dihydrocapsaicin and several lesser impurities. Separation by HPLC is required in order to obtain pure dihydrocapsaicin. Dihydrocapsaicin represents about 10% of the compound present in commercial preparations purporting to be pure capsaicin, but it has about the same pungency as capsaicin. VR1 (vanilloid receptor 1) is a heat activated calcium ion channel which functions as a part of the normal nociceptive pain pathway. Capsaicin elicits a sensation of burning pain by activation of VR1 on small, non-myelinated polymodal C-type nociceptive nerve fibers. The potency of dihydrocapsaicin at VR1 appears equivalent to capsaicin. Antioxidant. Reduces oxidation of serum lipids. Mutagenic. Dihydrocapsaicin is an activator of VR1.

Morroniside would act as a regulator of hepatic inflammatory reactions and lipid metabolism in db db mice. It exhibits protective effects against diabetic renal damage and human umbilical vein endothelial cells, by inhibiting hyperglycemia and oxidative s

Cimicifugoside H1 shows the protective function to cerebral neuron during cerebral ischemia.

MTP 131 is a mitochondria-targeted peptide antioxidant.1,2It localizes to the mitochondria and reducestert-butyl hydroperoxide-induced lipid peroxidation and apoptosis in SH-SY5Y cells when used at concentrations ranging from 0.001 to 1 nM.1MTP 131 (2 mg kg) reduces infarct volume, hemispheric swelling, and glutathione (GSH) depletion in a mouse model of acute cerebral ischemia induced by middle cerebral artery occlusion (MCAO).2It increases survival, improves motor function, and decreases degeneration of the lumbar spinal cord in a superoxide dismutase 1 mutant (SOD1G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS) when administered at a dose of 5 mg kg. MTP 131 reduces albuminuria, urinary hydrogen peroxide levels, and mesangial matrix accumulation, as well as preserves superoxide production, in adb dbmouse model of diabetic nephropathy.3 1.Zhao, K., Luo, G., Giannelli, S., et al.Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell linesBiochem. Pharmacol.70(12)1796-1806(2005) 2.Szeto, H.H.Mitochondria-targeted peptide antioxidants: Novel neuroprotective agentsAAPS J.8(3)E521-E531(2006) 3.Miyamoto, S., Zhang, G., Hall, D., et al.Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db db mice against progression of diabetic kidney diseaseJ. Biol. Chem.295(21)7249-7260(2020)

Keap1-Nrf2-IN-22 (compound 19) acts as a Keap1-Nrf2 inhibitor with a KD2 value of 42.2 nM. It is utilized in research focused on acute lung injury (ALI) and cerebral ischemia reperfusion (I R) injuries.

iNOs-IN-5 (Compound BN-4) is an inhibitor of iNOS with an IC50 value of 0.1707 μM, effectively reducing NO expression in RAW264.7 cells stimulated by LPS (HT-D1056). It further diminishes the expression of ROS and lactate dehydrogenase induced by hypoxic injury, displaying anti-necrotic and anti-apoptotic properties. In an SD rat model, iNOs-IN-5 exhibits neuroprotective effects against cerebral ischemia and is capable of crossing the blood-brain barrier.

HZS60 is a brain-penetrant NMDAR TRPM4 inhibitor that shows promise in ameliorating cerebral ischemia. It provides significant neuroprotection against ischemic injury in primary neurons caused by NMDA and oxygen-glucose deprivation reoxygenation. HZS60 demonstrates favorable pharmacokinetic properties and can inhibit cerebral ischemia-reperfusion injury, positioning it as a potential inhibitor for ischemic stroke.

L-701252, a potent glycine site NMDA receptor antagonist, exhibits an inhibition concentration (IC50) of 420 nM. Additionally, it offers marginal neuroprotection against global cerebral ischemia.

Licostinel (CGP 63446) is a glutamate receptor antagonist. Licostinel protects against permanent focal cerebral ischemia.

Oxysophoridine (Sophoridine N-oxide) has a protective effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic mechanisms; it may be a potential neuroprotective agent for cerebral ischemia injury, that the effect may be due to its ability to inhibit oxidative stress and expression of the N-methyl-D-aspartate receptor subunit NR1.Oxysophoridine ameliorates cardiac damage in a rat model of AMI and that this cardioprotection may be linked with its anti-oxidative, anti-apoptotic and anti-inflammatory properties.

ASN04885796 (compound IV) is a neuroprotective, specific GPR17 agonist with an EC50=2.27 nM for GPR17-mediated GTPγS binding and can be used to study neurodegenerative diseases such as cerebral ischemia and demyelinating diseases.

KUS121 is a valosin-containing protein (VCP) modulator that inhibits VCP ATPase activity (IC50= 330 nM).1It inhibits cell death, ATP depletion, and upregulation of C/EBP-homologous protein (CHOP) induced by tunicamycin, an inducer of ER stress, in HeLa cells when used at concentrations of 20, 50, and 50 μM, respectively. KUS121 (100 μM) inhibits ATP depletion and cell death induced by oxygen-glucose deprivation (OGD) in rat primary cortical neurons in anin vitromodel of cerebral ischemia.2It reduces infarction volume and increases the latency to fall in an accelerating rotarod test in a mouse model of focal cerebral ischemia induced by transient distal middle cerebral artery occlusion (MCAO) when administered at a dose of 100 mg/kg immediately following occlusion and again at 50 mg/kg following reperfusion. KUS121 (50 mg/kg) inhibits thinning of the retinal outer nuclear layer and preserves visual function in an rd10 mouse model of retinitis pigmentosa.1 1.Ikeda, H.O., Sasaoka, N., Koike, M., et al.Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosaSci. Rep.45970(2014) 2.Kinoshita, H., Maki, T., Yasuda, K., et al.KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletionSci. Rep.9(1)11519(2019)

Aptiganel hydrochloride（Cerestat） is the salt form of Aptiganel.Aptiganel is a non-competitive NMDA antagonist with neuroprotective effects used in the treatment of stroke and focal cerebral ischemia.

Verbenalin (Verbenaloside) induces angiogenesis via a programmed PI3K Akt eNOS VEGF signaling axis.

Forsythoside B binds to LPS and reduces the biological activity of serum LPS, and inhibits NF-κB activation. Forsythoside B inhibits the inflammatory response and has antioxidant properties. Potent neuroprotective effects with a favorable therapeutic time

Emodin-8-glucoside (Anthraglycoside B) functions to protect from focal cerebral injury induced by ischemia and reperfusion. Emodin-8-beta-D-glucoside directly stimulates cell proliferation and differentiation of osteoblasts.

Barlerin (8-O-Acetylshanzhiside methyl ester) has potential against cerebral ischemic injury, and its protective effect on oxygen-glucose deprivation-induced injury might be due to the suppression of intracellular Ca2+ elevation and caspase-3 activity, and improvement of mitochondrial energy metabolism.8-O-Acetylshanzhiside methylester can increase angiogenesis and improve functional recovery after stroke.8-O-Acetylshanzhiside methylester has protective effects on experimental myocardial ischemia injury, the effects might be due to block of myocardial inflammatory cascades through an HMGB1-dependent NF-κB signaling pathway.8-O-Acetylshanzhiside methylester protects diabetic brain against I R injury by alleviating diabetic cerebral I R injury and attenuating blood–brain barrier (BBB) breakdown, and its protective effects may involve HMGB-1 and NF-κB signalling pathway.