Nestronics
Nestronics
Ischemic stroke is also called brain ischemia and cerebral ischemia.
Ischemia is the medical term for "lack of blood supply." Most ischemic strokes occur
when an artery supplying the brain becomes blocked by a thrombus or embolus.
Important: Ischemic stroke must be distinguished from hemorrhagic stroke before
antiplatelet, anticoagulant, thrombolytic, or potentially blood-thinning therapies are used.
The compounds below include standard therapies, nutritional adjuncts, and experimental
neuroprotective compounds. They do not all have equivalent levels of clinical evidence.
| Mechanism | Top Compounds |
|---|---|
| Antiplatelet / secondary stroke prevention | Aspirin, Panax notoginseng/PNS, Ginkgo biloba/EGb 761, Salvia miltiorrhiza |
| Antioxidant / glutathione / ROS control | N-Acetylcysteine (NAC), Melatonin, CoQ10, EGCG, Curcumin, Quercetin |
| Mitochondrial protection | Melatonin, CoQ10, Resveratrol, Citicoline |
| Anti-inflammatory / NF-κB / cytokines | NAC, Melatonin, Curcumin, Luteolin, Baicalin |
| Membrane repair / cholinergic support | Citicoline, Alpha-GPC |
| BBB / neurovascular protection | Melatonin, Rosmarinic acid, Astragaloside IV |
| Nutritional deficiency / rehabilitation support | Vitamin D3, Vitamin B12, Folate, Magnesium |
| Experimental ischemic neuroprotection | Tocotrienols, Luteolin, Ferulic acid, Honokiol, Berberine, Huperzine A |
| Compound | Class | Primary Mechanisms | Key Stroke Effects | Evidence Level | Phase Utility | Human / Preclinical Dose Context | Clinical Translation Potential | |
|---|---|---|---|---|---|---|---|---|
| Aspirin / ASA | NSAID / antiplatelet drug | Irreversible COX-1 inhibition; ↓ thromboxane A2; ↓ platelet aggregation | Reduces recurrent ischemic stroke risk in appropriate non-cardioembolic ischemic stroke patients | Strong clinical; standard of care | Acute after hemorrhage is excluded + secondary prevention | Common long-term antiplatelet dose: approximately 75–100 mg/day; higher doses may be used in specific clinical circumstances | High; established benefit, but bleeding-risk limited | |
| N-Acetylcysteine (NAC) | Thiol antioxidant / glutathione precursor | ↑ glutathione; ↓ ROS; ↓ lipid peroxidation; anti-inflammatory effects; thiol/disulfide modulation; possible reduction of large VWF multimers | Preliminary human evidence for improved neurological and functional recovery; reduction of oxidative and inflammatory biomarkers; possible antithrombotic/VWF effects | Randomized human pilot studies + strong preclinical evidence | Acute / early recovery | No established routine post-stroke supplement dose. One clinical study used a 4 g loading dose followed by 4 g/day divided for 2 days; this is a research protocol, not a routine self-treatment dose | Moderate–High; promising human evidence but not standard therapy | |
| Melatonin | Indoleamine / neurohormone | ↓ ROS; mitochondrial protection; ↓ neuroinflammation; ↓ apoptosis; ↓ excitotoxicity; BBB protection; possible ↓ MMP-9 and NLRP3 signaling | Reduced ischemia-reperfusion injury in experimental models; preliminary human evidence suggests improved neurological and functional recovery | Preliminary randomized clinical + extensive preclinical evidence | Acute + recovery; sleep/circadian support | No established stroke-treatment dose. Low-dose sleep supplementation is commonly approximately 0.3–2 mg at night, while stroke trials have used study-specific pharmacological protocols | Moderate–High; favorable safety profile at conventional doses, promising but unproven stroke efficacy | |
| Vitamin D3 | Vitamin / secosteroid hormone precursor | Immune modulation; neurotrophic support; muscle function; vascular/endothelial support; calcium homeostasis | May improve neurological and functional rehabilitation outcomes, particularly in vitamin-D-deficient patients | Clinical studies + systematic review/meta-analysis; mixed but positive signal | Recovery / deficiency correction | Dose should be based on serum 25-OH-vitamin D status; no universal stroke-specific dose | Moderate–High when deficient | |
| Hydrogen Gas / Molecular Hydrogen | Therapeutic medical gas | ↓ ischemia/reperfusion oxidative stress; ↓ neuroinflammation; mitochondrial protection; ↓ apoptosis; BBB protection | Potential reduction of secondary neuronal injury and improvement in early neurological recovery | Small human RCT + substantial preclinical evidence | Primarily acute / early recovery | Clinical stroke study: 3% H₂ inhalation, 1 h twice daily for 7 days | Promising but experimental; chronic rehabilitation benefit unproven | |
| Coenzyme Q10 / CoQ10 | Mitochondrial cofactor / antioxidant | Supports mitochondrial electron transport; ↓ ROS; ↑ antioxidant capacity; anti-inflammatory effects | Human studies suggest reductions in oxidative stress and inflammatory biomarkers after ischemic stroke; possible neurological benefit | Small randomized human trials + preclinical evidence | Acute + recovery | Study-specific; no established post-stroke therapeutic dose. Common supplement doses are approximately 100–300 mg/day | Moderate; encouraging human evidence but not standard therapy | |
| Ginkgo biloba / EGb 761 | Standardized herbal extract | Cerebral microcirculation; antioxidant effects; platelet-activating-factor modulation; neuroprotection | May support post-stroke cognition and neurological recovery; not established for prevention of recurrent stroke | Clinical + preclinical; evidence stronger for standardized EGb 761 | Recovery / cognition | Approximately 120–240 mg/day standardized extract in many neurological studies | Moderate; bleeding interaction caution, especially with antiplatelet or anticoagulant drugs | |
| Panax notoginseng / PNS | Triterpene saponins | Anti-inflammatory; vascular/endothelial protection; microcirculation support; antiplatelet/antithrombotic effects; antioxidant activity | Improved neurological and blood-flow outcomes in some clinical studies; much evidence involves standardized PNS or Xuesaitong preparations | Clinical mainly from China + substantial preclinical evidence | Acute + recovery | Highly formulation-dependent; standardized extracts and injectable preparations cannot be directly equated with ordinary root supplements | Moderate; possible bleeding interaction | |
| Alpha-GPC / Alpha-glycerylphosphorylcholine | Choline donor / phospholipid precursor | ↑ acetylcholine; phosphatidylcholine synthesis; neuronal membrane support | May support cognitive and neurological recovery after stroke | Older human clinical evidence; modern confirmation limited | Recovery / cognition | Approximately 300–1200 mg/day in supplement/clinical use; no established modern stroke-treatment dose | Moderate; possible TMAO/cardiovascular concern remains uncertain | |
| Citicoline / CDP-choline | Choline donor / phospholipid precursor | ↑ phosphatidylcholine synthesis; membrane repair; ↓ free fatty acid release; cholinergic support | Strong mechanistic rationale and possible cognitive effects, but no demonstrated benefit in the large ICTUS acute-stroke trial | Clinical; large pivotal RCT negative, smaller/earlier studies mixed | Recovery / cognition | Approximately 500–2000 mg/day has been studied; no established effective post-stroke dose | Low–Moderate efficacy / good tolerability | |
| Salvia miltiorrhiza / Danshen | Herbal extract | Microcirculation; endothelial protection; antioxidant effects; antiplatelet activity | May support cerebral perfusion and neurological recovery; evidence often involves Chinese standardized or injectable preparations | Clinical mainly China + preclinical | Acute + recovery | Variable and formulation-dependent; no established dose for ordinary oral supplements after stroke | Moderate; bleeding and drug-interaction caution | |
| Vitamin B12 + Folate + Vitamin B6 | B vitamins / methylation cofactors | ↓ homocysteine; methylation support; endothelial and neurological function | Potential secondary-prevention relevance when homocysteine is elevated or B12/folate deficiency is present | Human clinical; mixed overall, stronger rationale in selected patients | Prevention / recovery / deficiency correction | Dose should be guided by B12, folate, renal function, and homocysteine status | Moderate when indicated | |
| Magnesium | Essential mineral | NMDA modulation; vascular tone; blood-pressure regulation; neuronal membrane stabilization | Supports normal vascular and neurological function; direct therapeutic benefit after established stroke remains uncertain | Nutritional/epidemiological support; limited treatment evidence | Prevention / recovery / deficiency correction | Prefer dietary adequacy and correction of deficiency; no established post-stroke therapeutic supplement dose | Moderate when deficient | |
| Omega-3 / EPA / DHA | Marine fatty acids | Lipid modulation; endothelial effects; inflammation modulation; membrane support | Cardiovascular risk-factor support, but ordinary fish-oil supplementation has not consistently reduced recurrent stroke | Human clinical; mixed for stroke-specific outcomes | Prevention / long-term vascular health | Prefer dietary fish intake; supplemental dose should be individualized, especially when combined with antithrombotic drugs | Moderate for cardiovascular support; Low–Moderate for stroke-specific benefit | |
| Baicalin | Flavonoid | Anti-inflammatory; anti-apoptotic; antioxidant; PI3K/Akt and related signaling | Reduced neuronal injury, inflammation, and infarct size in experimental ischemia models | Preclinical + limited clinical context | Experimental acute neuroprotection | No established human stroke dose | Low–Moderate | |
| Methylene Blue | Synthetic redox-active phenothiazine | Mitochondrial electron transport support; increased ATP production; reduced oxidative stress; enhanced mitophagy; reduced apoptosis; reduced AQP4-associated cerebral edema | Reduced infarct volume and improved neurological outcomes in transient ischemic stroke models; delayed penumbra progression in permanent ischemia models | Moderate preclinical; multiple rodent MCAO studies; no established human stroke efficacy | Experimental acute + reperfusion | No established human stroke dose | Rat studies: 0.5-10 mg/kg, depending on protocol and administration route. Approximate HED: 0.08-1.61 mg/kg (about 5.6-113 mg for 70 kg). Not a recommended human dose. | Moderate-Low (investigational); MAO-A inhibition, serotonin syndrome risk, G6PD contraindication, dose-dependent toxicity |
| Curcumin | Polyphenol | ↓ NF-κB; ↓ inflammatory cytokines; Nrf2 activation; antioxidant and anti-apoptotic effects | Reduced infarct size, oxidative stress, and neuroinflammation in experimental ischemia models | Strong preclinical; limited direct human stroke evidence | Experimental acute + recovery | General supplement doses commonly approximately 500–2000 mg/day depending on formulation; no established stroke dose | Low–Moderate; bioavailability and bleeding-interaction considerations | |
| Resveratrol | Polyphenol | SIRT1 activation; mitochondrial protection; antioxidant; anti-inflammatory; anti-apoptotic | Reduced apoptosis and ischemic brain injury in experimental models | Strong preclinical; limited direct clinical stroke evidence | Experimental acute + recovery | General supplement doses approximately 100–500 mg/day; no established stroke-treatment dose | Low–Moderate; low bioavailability | |
| EGCG | Green-tea catechin | ROS modulation; Nrf2-related antioxidant activity; vascular and mitochondrial protection | Reduced neuronal injury and oxidative stress in experimental models | Strong preclinical; little direct human stroke evidence | Experimental acute neuroprotection | Approximately 200–400 mg/day supplemental EGCG is commonly used; no established stroke dose | Low–Moderate; hepatotoxicity risk increases with high-dose extracts | |
| Quercetin | Flavonoid | Antioxidant; anti-inflammatory; anti-edema; endothelial protection | Reduced edema, oxidative injury, and infarct size in experimental ischemia models | Strong preclinical; limited direct clinical stroke evidence | Experimental acute neuroprotection | Approximately 500–1000 mg/day commonly used as a supplement; no established stroke dose | Low–Moderate | |
| Tocotrienols | Vitamin E subfamily | Lipid antioxidant; membrane protection; anti-inflammatory and neuroprotective signaling | Neuroprotection and reduced ischemic injury in experimental models | Preclinical + limited human neurological evidence | Experimental acute / prevention | Approximately 100–300 mg/day commonly used in supplements; no established stroke dose | Low–Moderate | |
| Luteolin | Flavonoid | ↓ NF-κB; Nrf2 activation; PI3K/Akt modulation; anti-inflammatory; anti-apoptotic effects | Reduced inflammation and neuronal injury in experimental stroke models | Strong preclinical | Experimental acute neuroprotection | No established human stroke dose | Low | |
| Ferulic acid | Phenolic acid | Antioxidant; vasodilation; endothelial and vascular protection | Improved cerebral blood flow and reduced neuronal injury in experimental models | Preclinical | Experimental acute neuroprotection | No established human stroke dose | Low | |
| Rosmarinic acid | Phenolic acid | BBB protection; antioxidant; anti-inflammatory; anti-apoptotic | Reduced BBB disruption, edema, and inflammatory injury in experimental ischemia models | Preclinical | Experimental acute neuroprotection | No established human stroke dose | Low | |
| Berberine | Isoquinoline alkaloid | AMPK activation; metabolic regulation; anti-inflammatory, antioxidant, and endothelial effects | Neuroprotection in experimental ischemia; may also improve metabolic vascular risk factors | Predominantly preclinical for stroke | Prevention + experimental recovery | Approximately 500–1500 mg/day commonly used metabolically; no established stroke-treatment dose | Low–Moderate; substantial drug-interaction potential | |
| Huperzine A | Alkaloid / acetylcholinesterase inhibitor | AChE inhibition; ↑ acetylcholine; possible NMDA modulation and neuroprotection | Potential support for post-stroke cognitive dysfunction, but direct clinical evidence is limited | Preclinical + indirect cognitive clinical evidence | Experimental recovery / cognition | Approximately 100–200 µg/day commonly used; no established stroke-treatment dose | Low; cholinergic adverse effects may limit use | |
| Honokiol | Biphenolic lignan | Mitochondrial protection; antioxidant; anti-inflammatory; anti-apoptotic effects | Reduced ischemic neuronal injury in experimental models | Preclinical | Experimental acute + recovery | No established human stroke dose | Low |
| Compound | Class | Primary Mechanisms | Key Stroke Effects | Evidence Level | Phase Utility | Human Dose Range | Approx. HED mg/kg/day | Practical Therapeutic Index |
|---|---|---|---|---|---|---|---|---|
| Edaravone | Synthetic free-radical scavenger | ROS reduction; lipid peroxidation inhibition; mitochondrial and endothelial protection | May reduce acute ischemic neuronal injury; clinical benefit varies across studies | Human clinical; approved for ischemic stroke in Japan | Acute | 30 mg IV twice daily, up to 14 days (Japanese regimen) | Not applicable; direct human clinical dose available | Moderate-High; clinical use, but renal and other safety considerations |
| Cerebrolysin | Porcine brain-derived peptide mixture | Neurotrophic signaling; neuronal survival; neuroplasticity; anti-apoptotic effects | Investigated for neurological and motor recovery; clinical benefit remains unproven | Human RCTs; mixed results and possible serious adverse events | Acute + rehabilitation | 10-50 mL/day IV in clinical studies; formulation-specific | Not applicable; clinical dosing expressed in mL | Low-Moderate; uncertain benefit-risk balance |
| N-Acetylcysteine (NAC) | Cysteine derivative / glutathione precursor | GSH synthesis increase; ROS reduction; mitochondrial protection; NF-kB modulation | Reduced oxidative injury and infarct size in experimental ischemia models | Preclinical + limited human stroke research | Experimental acute + recovery | No established stroke dose; 600-1800 mg/day oral used for other indications | No validated stroke HED; 600-1800 mg/day equals 8.6-25.7 mg/kg for a 70 kg adult, not a preclinical conversion | Moderate; established use elsewhere, stroke efficacy uncertain |
| Omega-3 Fatty Acids (DHA/EPA) | Polyunsaturated fatty acids | Membrane phospholipid support; resolvin and protectin production; neuroinflammation reduction | Neuroprotection in experimental stroke; human secondary-prevention benefit uncertain | Human cardiovascular research + preclinical stroke studies | Prevention + recovery | No established stroke dose; 1-4 g/day EPA+DHA studied for other indications | Not established for stroke; clinical human doses available | Moderate; bleeding and atrial fibrillation considerations at higher doses |
| Sulforaphane | Isothiocyanate / broccoli-derived compound | NRF2 activation; HO-1 increase; oxidative stress reduction; ferroptosis and neuroinflammation modulation | Reduced infarct volume and neuronal injury in experimental ischemia-reperfusion models | Preclinical stroke evidence | Experimental acute + recovery | No established stroke dose; human studies use variable sulforaphane or glucoraphanin formulations | Study-specific; no validated stroke HED | Moderate-Low; promising mechanism, formulation and bioavailability uncertainties |
| Magnesium | Essential mineral / NMDA modulator | NMDA receptor modulation; calcium influx regulation; excitotoxicity reduction | Neuroprotective in experimental models; large acute-stroke trials did not show improved functional outcomes | Large human clinical trials; negative acute efficacy | Acute investigated; deficiency correction when indicated | FAST-MAG: 4 g IV loading followed by 16 g infusion over 24 hours (magnesium sulfate) | Not applicable; direct human trial regimen | Low for acute stroke efficacy; IV administration requires monitoring |
| Taurine | Sulfonic amino acid derivative | Calcium homeostasis; mitochondrial protection; excitotoxicity and oxidative stress reduction | Reduced neuronal injury in experimental cerebral ischemia models | Preclinical stroke evidence | Experimental acute + recovery | No established stroke dose; 1-3 g/day used in other human studies | No validated stroke HED | Moderate-Low; generally tolerated, efficacy unproven |
| Apigenin | Flavonoid | NF-kB inhibition; NLRP3 suppression; anti-apoptotic and antioxidant effects | Reduced neuroinflammation and ischemic neuronal injury in animal models | Preclinical | Experimental acute | No established human stroke dose | Study-specific; no validated stroke HED | Low-Moderate; limited pharmacokinetic data |
| Pterostilbene | Stilbenoid / resveratrol analogue | SIRT1 and AMPK modulation; mitochondrial protection; oxidative stress and apoptosis reduction | Reduced ischemic neuronal damage in preclinical studies | Preclinical stroke evidence | Experimental acute + recovery | No established stroke dose; 50-250 mg/day studied for other indications | No validated stroke HED | Low-Moderate; limited long-term clinical evidence |
| Ursolic Acid | Pentacyclic triterpenoid | NRF2 signaling; NF-kB inhibition; oxidative stress and apoptosis reduction | Neuroprotective effects in experimental cerebral ischemia-reperfusion models | Preclinical | Experimental acute + recovery | No established human stroke dose | Study-specific; no validated stroke HED | Low; limited bioavailability and clinical evidence |
| Gastrodin | Phenolic glycoside / Gastrodia elata | Oxidative stress reduction; ferroptosis inhibition via GPX4-related signaling; anti-inflammatory effects | Improved neurological scores in some clinical studies; reduced infarct injury in animal models | Preclinical + small regional clinical trials; evidence quality limitations | Acute + recovery investigated | Formulation-dependent; no internationally established stroke dose | Study-specific; no validated stroke HED | Moderate-Low; promising but insufficient validation |
| Glycine | Amino acid / neurotransmitter | Inhibitory glycine receptor activation; NMDA receptor co-agonism; context-dependent excitotoxicity | Experimental neuroprotection reported; NMDA co-agonism may complicate effects | Limited preclinical stroke evidence | Experimental | No established human stroke dose | No validated stroke HED | Low; uncertain net effect on ischemic injury |
| Silver Nanoparticles (AgNPs) | Metal nanoparticles / experimental antiplatelet | Formulation-dependent platelet aggregation inhibition; GPIIb/IIIa activation down; P-selectin down; TXB2 down; MMP-1/MMP-2 release down. Other formulations increase platelet activation, calcium signaling and thrombin generation. | Potential antithrombotic activity demonstrated in experimental platelet systems. No demonstrated prevention or treatment benefit in human ischemic stroke. Some AgNPs are prothrombotic. | Preclinical; conflicting in-vitro and animal evidence; no established clinical stroke efficacy | Experimental prevention / antithrombotic research | No established human therapeutic dose | No validated HED. In-vitro antiplatelet concentrations: 50-100 micrograms/mL for selected 2-3.7 nm functionalized AgNPs. These are not human doses. | Low / undetermined; possible prothrombotic effects, hemolysis, oxidative toxicity and nanoparticle accumulation |
Nestronics is a supporter of the concept that all matter and life has been designed, and the designer is our Lord and God.
He is worth of all praise as his creation is truely amazing.
Use of this web site is acknowledgment of compliance with this Disclaimer