Tau-aggregation and neuroinflammation-IN-1 is a potent inhibitor of tau protein aggregates, showing significant inhibitory activity against AcPHF6 and full-length tau protein aggregates. Tau-aggregation and neuroinflammation-IN-1 has anti-inflammatory activity and reduces NO release.Tau-aggregation and neuroinflammation-IN-1 has low cytotoxicity against LSP-stimulated BV2 cells.Tau-aggregation and neuroinflammation-IN-1 reverses okadaic acid-induced memory impairment in rats.

Anti-neuroinflammation Agent 1 effectively modulates BV2 microglia cell polarization, shifting from an M1 to an M2 phenotype [1].

Polygalacic acid (Virgaureagenin G)(PA) significantly improves cholinergic system reactivity, as indicated by decreased acetylcholinesterase (AChE) activity, increases choline acetyltransferase (ChAT) activity, and elevates levels of acetylcholine (ACh) in the hippocampus and frontal cortex, PA also significantly ameliorates neuroinflammation and oxidative stress in mice; suggest that PA might exert a significant neuroprotective effect on cognitive impairment, driven in part by the modulation of cholinergic activity and neuroinflammation. Polygalacic acid shows significant postingestive effects on Spodoptera littoralis larvae.

MW01-2-151SRM is a novel small molecule inhibitor of microglia activation that crosses the blood-brain barrier, has anti-neuroinflammatory effects, attenuates the up-regulation of glial cytokines in models of neuroinflammation, and can be used in studies of traumatic brain injury, Alzheimer's disease, and alginate toxicity.

MSC 2032964A is a potent selective ASK1 inhibitor (IC50 = 93 nM) that is oral bioavailable and brain permeable. It inhibited neuroinflammation in mouse EAE models and blocked LPS-induced phosphorylation of ASK1 and p38 in cultured mouse astrocytes.

Golexanolone (Golexanolona) is a novel GABA-A receptor-modulating steroid antagonist that reduces peripheral inflammation and neuroinflammation and improves cognitive and motor function in rats with chronic hyperammonemia, and may be used to study hepatic encephalopathy.

Sulfosuccinimidyl oleate (Sulfo-N-succinimidyl oleate) (Sulfo-N-succinimidyl oleate) is a long chain fatty acid that inhibits fatty acid transport into cells. Sulfosuccinimidyl oleate is a potent and irreversible inhibitor of mitochondrial respiratory chain. Sulfosuccinimidyl oleate binds the CD36 receptor on the surface of microglia. Sulfosuccinimidyl oleate is neuroprotective and alleviates stroke-induced neuroinflammation [1] [2].

INT-777 (S-EMCA) is a potent TGR5 agonist with an EC50 of 0.82 μM. INT-777 (S-EMCA) inhibits NLRP5-ASC inflammasome-mediated neuroinflammation via the TGR3/cAMP/PKA signaling pathway after subarachnoid hemorrhage in rats.

MTOB (α-keto-γ-Methylthiobutyric acid) is a substrate for c-terminal binding protein (CtBP) that interferes with the carcinogenic activity of CtBP in cell culture and mice. It also actively regulates TCF-4 signaling, leading to cancer stem cell (CSC) growth and self-renewal.

Deferoxamine（Desferrioxamine B） is an iron chelator (binds Fe(III) and many other metal cations) that inhibits neuronopathy, may be used to modify the reduction of iron accumulation and deposition in tissues, and may improve neurological dysfunction by inhibiting ferroptosis and neuroinflammation following traumatic brain injury.Desferrioxamin-B has antioxidant, antiproliferative, Deferoxamine has antioxidant, antiproliferative, and antitumor activities, and can induce HIF-1α production, apoptosis and autophagy in cancer cells.Desferrioxamin-B can be used in the treatment of acute iron toxicity and COVID-19 related diseases.

ICILIN (AG-3-5) is a synthetic TRPM8 ion channel super-agonist.

SUCNR1-IN-2 (Statement 35) serves as an inhibitor of both succinate and succinate receptor 1, utilized in research pertaining to neurodegenerative disorders, including neuroinflammation [1].

Methylene Blue (Basic Blue 9) hydrate functions as an inhibitor of guanylyl cyclase (sGC), monoamine oxidase A (MAO-A), and NO synthase (NOS). This compound, known for its vasopressor activity, is widely utilized as a dye in various medical procedures. It operates via the nitric oxide synthase/guanylate cyclase signaling pathway to diminish prepulse inhibition and possesses the capacity to cross the blood-brain barrier. Methylene Blue hydrate acts as a REDOX cycling compound and inhibits Tau protein aggregation. Moreover, it is effective in reducing cerebral edema, damping microglial activation, and alleviating neuroinflammation, demonstrating its multifaceted therapeutic potential [1] [2] [3].

Ulmoidol mitigates neuroinflammation by inhibiting the PU.1 (transcriptional) signaling pathway.

MKEY, a synthetic cyclic peptide inhibitor of CXCL4-CCL5 heterodimer formation, has been shown to protect against atherosclerosis and aortic aneurysm formation by mediating inflammation, but whether it modulates neuroinflammation and brain injury has not

ER176 is a novel PET radioligand utilized for the visualization of 18 kDa translocator protein (TSPO), a neuroinflammation biomarker, marking the advancement in imaging technology.

The quinuclidine PHA 568487 free base is an agonist of the alpha 7 nicotinic acetylcholine receptor that was designed to mitigate the bioactivation associated with the core scaffold and subsequently remove associated liabilities with in vivo tolerability.

C 101248 is a selective and potent inhibitor targeting both mouse and human tandem pore domain halothane-inhibited K+ channel 1 (THIK-1, IC50= 50 nM), without affecting the K2P family members (TREK-1, TWIK-2) and Kv2.1. This compound effectively blocks tonic and ATP-evoked THIK-1 K+ currents as observed in whole-cell patch-clamp recordings of mouse hippocampal microglia. Additionally, C 101248 mitigates neuroinflammation by inhibiting the NLRP3-dependent release of IL-1β in isolated microglia.

Nrf2 Activator-8 (Compound 10e), with an EC50 of 37.9 nM, is a potent Nrf2 activator that demonstrates significant antioxidant and anti-inflammatory properties in BV-2 microglial cells. Furthermore, this compound notably ameliorates spatial memory deficits in a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation [1].

Phenoxybenzamine is an α-1 adrenergic receptor antagonist. Phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after traumatic brain injury.

PMX-205 is a cyclic hexapeptide that acts as a potent antagonist of C5a receptor (C5aR; IC50= 31 nM).1It is orally active and blocks inflammatory signaling and symptoms in animal models of colitis and allergic asthma.2,3PMX-205 is also brain penetrant and reduces neuroinflammation and neurodegeneration in an animal model of Alzheimer's disease.4 1.March, D.R., Proctor, L.M., Stoermer, M.J., et al.Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activityMol. Pharmacol.65(4)868-879(2004) 2.Jain, U., Woodruff, T.M., and Stadnyk, A.W.The C5a receptor antagonist PMX205 ameliorates experimentally induced colitis associated with increased IL-4 and IL-10Br. J. Pharmacol.168(2)488-501(2013) 3.Staab, E.B., Sanderson, S.D., Wells, S.M., et al.Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthmaInt. Immunopharmacol.21(2)293-300(2014) 4.Fonseca, M.I., Ager, R.R., Chu, S.-H., et al.Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's diseaseJ. Immunol.183(2)1375-1383(2009)

Cudratricusxanthone A has potent anti-proliferative, antioxidative, and monoamine oxidase inhibitory effects, it also possesses anti-cancer activities and provide a basis for developing effective therapeutic agents to inhibit growth and metastasis of brea

DNL343, a brain-penetrating eIF2B (eukaryotic initiation factor 2B) activator, suppresses the abnormal integrated stress response (ISR). By inhibiting ISR activity in the central nervous system (CNS), DNL343 ameliorates neurodegeneration and neuroinflammation. Additionally, it protects against motor dysfunction and premature death in eIF2B loss-of-function (LOF) mutant mice and demonstrates inhibitory potential for vanishing white matter disease (VWMD) characterized by eIF2B LOF and persistent ISR activation [1].

MY33-3 is a powerful and specific inhibitor of receptor protein tyrosine phosphatase (RPTP)β/ζ, demonstrating an IC50 value of approximately 0.1 μM. Moreover, MY33-3 exhibits inhibitory activity against PTP-1B with an IC50 value of about 0.7 μM. Additionally, MY33-3 has been shown to effectively decrease ethanol consumption and alleviate neuroinflammation and cognitive dysfunction induced by Sevoflurane.

GIBH-130 markedly inhibits the IL-1β secretion by activated microglia (IC50: 3.4 nM). GIBH-130 is an effective inhibitor of neuroinflammation.

EVT-401 (P2X7 receptor antagonist-1), a purinergic P2X7 receptor antagonist, demonstrates efficacy in combating neuroinflammation [1].

Obtucarbamate A isolated from Disporum cantoniense has antitussive activity.It has antitussive activity, it exhibits significant inhibitory effect against neuroinflammation with the IC50 value of 10.57 μM .

Artemisinin B is a drug which may improve spatial memory in dementia patients and alter the levels of inflammatory cytokines in the hippocampus and the cortex. Artemisinin B may inhibit neuroinflammation and exert neuroprotective effects on cognitive functions by modulating the TLR4-MyD88-NF-κB signaling pathway. Artemisinin B has shown potential in the treatment of neuroinflammatory diseases.

1. Obtusifolin has antioxidant properties and improves chemically induced diabetes and its complications by modulation of oxidative stress. 2. Obtusifolin suppresses phthalate esters-mediated bone resorption, thus may be a novel anti-breast-cancer bone me

Lonchocarpic acid shows an anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation.

Umibecestat, also known as CNP-520, is a beta-secretase inhibitor and is a drug candidate for prevention trials in Alzheimer's disease. CNP520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid (CSF) Aβ in rats and dogs, and Aβ plaque deposition in APP-transgenic mice. CNP520 reduces Aβ load and neuroinflammation in APP‐transgenic mice

Anti-inflammatory agent 56 (Compound 9), a selective COX-2 inhibitor with an IC50 of 0.54 μM, exhibits anti-oxidant and anti-inflammatory properties by inhibiting oxidative stress-induced cell death and neuroinflammation through the suppression of Keap1, COX-2, and iNOS. It also demonstrates low acute toxicity in mice with an LD50 of 1000 mg/kg [1].

Linderone, a compound isolated from Lindera erythrocarpa, has antioxidant and anti-inflammatory activity and can be used to study neuroinflammation.

SRI-42127 is a novel small molecule inhibitor of the RNA regulatory factor HuR, which inhibits tumor growth, attenuates glial activation in a lipopolysaccharide-induced neuroinflammation model, and reduces neuropathic pain after nerve injury by inhibiting the neuroinflammatory response.

sEH/AChE-IN-2 and acetylcholinesterase ( AChE ). sEH/AChE-IN-2 provides cumulative effects against neuroinflammation and memory impairment. sEH/AChE-IN-2 has the potential for the research of Alzheimer's disease (AD) .

MY33-3 hydrochloride is a potent and selective inhibitor of the protein tyrosine phosphatase RPTPβ/ζ (IC50~0.1 μM). MY33-3 hydrochloride inhibits PTP-1B (IC50~0.7 μM). MY33-3 hydrochloride reduces ethanol consumption and alleviates Sevoflurane-induced neuroinflammation and cognitive dysfunction.

Protosappanin A (PTA) has anti-oxidative/nitrative activities on brain immune and neuroinflammation through regulation of CD14/TLR4-dependent IKK/IκB/NF-κB inflammation signal pathway; it exerts anti-neuroinflammatory effect by inhibiting JAK2-STAT3 pathway in lipopolysaccharide-induced BV2 microglia. Protosappanin A induces immunosuppression of rats heart transplantation targeting T cells in grafts via NF-kappaB pathway. Protosappanin A and protosappanin B have antimicrobial activity, they show both alone activities and resistance reversal effects of amikacin and gentamicin against MRSA. Protosappanin A shows strong effect against HIV-1 IN with an IC50 value of 12.6 uM.

sEH/AChE-IN-1 (Compound 12a) is a dual inhibitor of soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE). sEH/AChE-IN-1 has a cumulative effect against neuroinflammation and memory impairment. sEH/AChE-IN-1 has shown research potential in Alzheimer's disease (AD).

Isonardosinone shows potential role in the treatment of neuroinflammation conditions, it inhibits NF-κB- and MAPK-mediated inflammatory pathways.

Amantadine hydrochloride (CI-719) is an antiviral that is used in the prophylactic or symptomatic treatment of influenza A and Parkinson disease.

PB131, a selective and brain-permeable HDAC6 inhibitor, exhibits high binding affinity (IC50: 1.8 nM) and potent anti-inflammatory activity, making it suitable for inflammation research, particularly in neuroinflammation [1].

CIAC001, a pyruvate kinase PKM2 inhibitor, exhibits anti-neuroinflammatory properties. It effectively suppresses LPS-induced production of proinflammatory nitric oxide (NO) and provides protection to immunologically active BV-2 cells with an IC50 value of 2.5 μM. Additionally, CIAC001 demonstrates anti-neuroinflammation effects in mouse models and attenuates chronic morphine-induced addiction [1].

P2X7 receptor antagonist-2 is a highly potent antagonist of the P2X7 receptor, exhibiting a pIC50 value range of 6.5-7.5. Its efficacy in combating neuroinflammation has been demonstrated [1].

NF-κB-IN-4 (compound 17) is a potent inhibitor of NF-κB pathway which can cross blood brain barrier (BBB). NF-κB-IN-4 shows potential anti-neuroinflammatory activity with low toxicity which can be used for the research of neuroinflammation related diseases. NF-κB-IN-4 can block the IκBα activation and phosphorylation, reduce NLRP3 expression, therefore inhibiting NF-κB activation [1].

Jaceosidin has anti-oxidative activity. Jaceosidin has anti-inflammatory activity, also a microglial inhibitor with anti-neuroinflammation activity. aceosidin has anticancer activity, modulates the ERK/ATM/Chk1/2 pathway, leading to inactivation of the Cd

Trofinetide, derived from the neuroprotective tripeptide Gly-Pro-Glu (an N-terminal sequence of insulin-like growth factor-1, IGF-1), shows promise in various neuroprotective models. At a concentration of 10 nM, it mitigates cell death in primary rat embryonic striatal neurons caused by okadaic acid. Additionally, Trofinetide reduces the expression of pro-inflammatory markers (IL-1β, TNF-α, IL-6, and E-selectin) in a rat model simulating neuroinflammation from penetrating ballistic-like brain injuries. In cases of brain injury induced by middle cerebral artery occlusion (MCAO), administration of Trofinetide at 30 and 60 mg/kg reduces the area of cortical and striatal infarct. Furthermore, a daily dose of 100 mg/kg reverses social recognition and contextual fear conditioning deficits, diminishes the number of dendritic spines, and decreases testicular weight gain in an fmr1-/- knockout mouse model of fragile X syndrome. Trofinetide formulations have been employed in treating Rett syndrome, highlighting its versatility across various neurological conditions.

Astramembrangenin (Cycloastragenol (Astramembrangenin)) is a triterpenoid saponin compound and a hydrolysis product of the main active ingredient in Astragalus membranaceus. Cycloastragenol (CAG) may have a novel therapeutic role in depression

1. Tiliroside (Tribuloside) shows anticarcinogenic activity. 2. Tiliroside shows hepatoprotective activity. 3. Tiliroside shows antioxidant and anti-inflammatory activity, can inhibit neuroinflammation in neurodegenerative disorders. 4. Tiliroside has anti-diabetic effect, are at least partially mediated through inhibitory effects on carbohydrate digestion and glucose uptake in the gastrointestinal tract. 5. Tiliroside and gnaphaliin are antioxidants against in vitro Cu(2+)-induced LDL oxidation in the same order of magnitude compared to that of the reference drug, probucol. 6. Tiliroside enhances fatty acid oxidation via the enhancement adiponectin signaling associated with the activation of both AMP-activated protein kinase and peroxisome proliferator-activated receptor α and ameliorates obesity-induced metabolic disorders.

Potent and selective CB2 receptor agonist (Ki = 12.8 nM; EC50 = 38.67 nM). Exhibits negligible affinity for the CB1 receptor (Ki > 40,000 nM) and no activity at the GPR55. Suppresses neuroinflammation by reducing microglial activation in a multiple sclerosis mouse model. BBB permeable; anti-inflammatory and neuroprotective.

AChE/PDE4-IN-1 (compound 12c) is a highly effective and specific dual inhibitor of PDE4 and AChE, with IC50 values of 0.28 μM and 1.88 μM for AChE and PDE4D, respectively. This compound demonstrates notable potential in reducing neuroinflammation associated with Alzheimer's disease research [1].