Cholinesterase (ChE)

CV-6209 is a potent antagonist of the platelet-activating factor (PAF) receptor.

Physostigmine, a parasympathomimetic alkaloid, is a reversible cholinesterase inhibitor. It extracts from the Calabar bean.

Timosaponin AIII (Timosaponin A3) induces autophagy in HeLa cells followed by apoptotic cell death (IC50: 10 μM). The Timosaponin AIII cellular response is mediated via inhibition of mTORC1 and induction of ER stress (IC50: 2.5 μM, BT474 cells; 6 μM, MDAMB231). The Timosaponin AIII pro-apoptotic response is selective for tumor cells over normal cells but autophagy is induced in both.

1. Swertianolin (Bellidifolin-8-O-Glucoside), mangiferin, rhodenthoside A-C, isoorientin, isovitexin, and amarogentin would serve as potential chemotaxonomic markers to differentiate Gentianaceae species. 2. Swertianolin and swertiamarin show significant hepatoprotective effect in the liver damage model induced by alpha-naphthylisot hiocyanate. 3. Swertianolin shows anti-acetylcholinesterase activity effects. 4. Swertianolin shows that it can scavenge superoxide and hydroxyl radicals with the studying method of the autoxidation of Pyrogallol and afenton.

Vamicamide (FK 176) is a novel anticholinergic compound. Vamicamide increases spontaneous locomotor activity in mice at 32 mg kg (p.o.) or higher and inhibits cataleptic convulsions in mice at 100 mg kg.

Simpinicline (OC-02) (OC-02) is a highly selective nicotinic acetylcholine receptor (nAChR) agonist that activates the trigeminal parasympathetic pathway and can be used to treat dry eye.

Rovatirelin (S-0373) is a newly synthesized thyrotropin-releasing hormone (TRH) analog that ameliorates cytosine arabinoside-induced motor dysfunction in a rat model of spinal cerebellar degeneration via acetylcholine and dopamine neurotransmission.

Donepezil (Aricept) is a piperidine-based, potent, specific, and reversible inhibitor of acetylcholinesterase (AChE). It can be used for the treatment of mild to moderate dementia of the Alzheimer's type.

Tenuifolin has no inherent toxicity to either the transfected or wild type cells at the effective concentrations, it inhibits amyloid-β secretion in vitro.

Garcinol also inhibits histone acetyltransferases (HATs, IC50= 7 μM) and p300 CPB-associated factor (PCAF, IC50 = 5 μM). Garcinol has anti-inflammatory and anti-cancer activity. Garcinol, a polyisoprenylated benzophenone harvested from Garcinia indica, exerts anti-cholinesterase properties towards acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50s of 0.66 μM and 7.39 μM, respectively.

Clozapine N-oxide dihydrochloride, a derivative of Clozapine and an agonist of human muscarinic design receptors (DREADDs), crosses the blood-brain barrier and activates DREADD receptors hM3Dq and hM4Di.

Ursolic acid acetate (Acetylursolic acid) has cytotoxic activity, antimalarial activity, antitumor and anticancer activities. Acetylursolic acid has NO production inhibitory activities. Acetylursolic acid has inhibition against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes.

Nodakenin ((+)-Marmesinin) is a compound with anti-allergic and anti-inflammatory activities.

1. Epiberberine may be caused drug interactions based on CYP2D6 enzyme. 2. Epiberberine has anti-adipogenic effect is mediated by downregulation of the Raf MEK1 ERK1 2 and AMPKα Akt pathways during 3T3-L1 adipocyte differentiation. 3. Epiberberine, as the brightest FSA emitter among the alkaloids, can also serve as an efficient conformation probe for HTG DNA and discriminate the DNA G-quadruplex from the RNA counterpart.

Epiberberine chloride, a natural pro-berberine from Coptis chinensis Franch. is an AChE, BChE, and BACE1 inhibitor with IC50 values of 1.07, 6.03, and 8.55 μM, respectively.Epiberberine chloride has antioxidant effects and inhibits the effects of Ca9-22 and Fa2R. Epiberberine chloride has antioxidant effects, inhibits the motility of Ca9-22 and FaDu cell lines, and can be used to study hyperlipidemia, Alzheimer's disease and diabetes.

Kuwanon U (4'-methoxykuwanon E), a compound from Morus alba, is a cholinesterase inhibitor with antimicrobial activity, inhibits acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and exerts its inhibitory effect by preventing ATP binding in the cytoplasmic domain of SERCA1, which can be used in the study of diabetes mellitus and bacterial infections.

1. Sinapine, an alkaloid from seeds of the cruciferous species, can be used as an effective natural compound for chemo-resistance. 2. Sinapine has antioxidant and radio-protective activities.

Jatrorrhizine chloride (Neprotine chloride) is a potent and orally active uptake-2 transporter inhibitor. It exhibits a critical neuroprotective role in H2O2-induced apoptosis via inhibition of the MAPK pathway in HT22 hippocampal neurons.

O-Desmethyl Galanthamine (Sanguinine) is a galanthamine-type alkaloid and an acetylcholinesterase (AChE) inhibitor with an IC50 of 1.83 μM.

Loganin (Loganoside), an iridoid glucoside, has been reported to be an inhibitor of Cox-1 and also noted to suppress TNF-α formation. This compound also has displayed potent free-radical-scavenging activity and inhibitory effects on melanogenesis.

N-p-trans-Coumaroyltyramine is a natural product and an acetylcholinesterase (AChE) inhibitor with an IC50 of 122 μM. It also exhibits anti-trypanosomal activity with an IC50 of 13.3 μM for T. brucei rhodesiense.

Galanthamine (Galantamine) is an acetylcholinesterase (AChE)inhibitor(IC50 : 500 nM), can reduce brain damage induced by hypoxia-ischemia.

Jatrorrhizine (neprotin) is a protoberberine alkaloid isolated from Enantia chlorantha (Annonaceae) and other species. It was found to have antimicrobial and antifungal activity. It binds and noncompetitively inhibits monoamine oxidase (IC50 4 micromolar for MAO-A and 62 for MAO-B).

Lobetyolinin is a compound from Codonopsis pilosula with acetylcholinesterase (AChE) inhibitory and antiarrhythmic activities.

Dehydroevodiamine (DHE), a natural compound isolated from Evodia rutaecarpa, can inhibit AChE. It has hypotensive and neuroprotective effects and modulates nitric oxide production.

Buntanetap ((+)-Phenserine) is an orally active inhibitor of polyneurotoxic proteins (TINAPs) for the study of neurological disorders, endocrine and metabolic disorders, and cardiovascular diseases.

1. Palmatine (Burasaine) is an inhibitor of dopamine generation. 2. Palmatine could potentially be developed for the treatment of flavivirus infections. 3. Palmatine has been used in the treatment of jaundice, dysentery, hypertension, inflammation, and liver-related diseases.

Protriptyline Hydrochloride is the hydrochloride salt form of protriptyline, a tricyclic secondary amine with an antidepressant property. Protriptyline hydrochloride (Protriptyline HCl) blocks the re-uptake of norepinephrine and serotonin by nerve terminals, thereby increasing available norepinephrine and serotonin. In addition, this agent exhibits anticholinergic activity.

Chikusetsusaponin Ib (Chikusetsu saponin Ib) is an inhibitor of AChE and can be used in studies about anti-Alzheimer's diseases.

Neoeriocitrin is a natural product isolated from Drynaria Rhizome, shows activity on proliferation and osteogenic differentiation in MC3T3-E1. Neoeriocitrin is a potent acetylcholinesterase (AChE) inhibitor.

PE 154 is a potent fluorescent inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50s of 280 pM and 16 nM respectively. PE 154 is commonly used to label β-amyloid plaques in histochemical analysis.

1. Corynoline ((+)-Corynoline) is an acetylcholinesterase inhibitor.

Rhodiosin is a compound with antioxidant activity.

Donepezil HCl(Aricept) is a selective and effective AChE inhibitor for bAChE and hAChE (IC50: 8.12 11.6 nM).

1. Huperzine-B is a efficient inhibitor of human brain AChE. 2. Huperzine-B can enhance ognitive and protect neuro, may be potentially new drug candidates for Alzheimer's disease therapy.

Lycoramine is a natural product isolated from Lycoris radiate. Lycoramine is a potent acetylcholinesterase (AChE) inhibitor

sn-Glycero-3-phosphocholine (Choline glycerophosphate) is a natural choline compound found in the brain and in milk. It is also a parasympathomimetic acetylcholine precursor which may have a potential for the treatment of Alzheimer's disease and dementia. sn-Glycero-3-phosphocholine rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of the acetylcholine neurotransmitter. It is a non-prescription drug in most countries due to its Generally Recognised As Safe (GRAS) status [1]. Studies have investigated its efficacy for cognitive disorders including stroke and Alzheimer's disease. An Italian multicentre clinical trial on 2, 044 patients suffering from recent stroke were supplied Glycerylphosphorylcholine in doses of 1, 000 mg day for 28 days and 400 mg three times per day for the five ensuing months. The trial confirmed the therapeutic role of alpha-GPC on the cognitive recovery of patients based on four measurement scales, three of which reached statistical significance [2].

Arjunolic acid has antioxidant, anti-inflammatory, antinociceptive and anticholinesterasic (AChE and BuChE) activities, it may as promising targets for the development of innovative multi-functional medicines for Alzheimer desease treatment.

1. Linarin (Acacetin-7-O-rutinoside) (acacetin-7-O-β-d-rutinoside) shows selective dose dependent inhibitory effect on acetylcholinesterase. 2. Linarin alleviates GalN LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways. 3. Linarin prevents A beta-induced neurotoxicity through the activation of PI3K Akt, which subsequently inhibits GSK-3b and up-regulates Bcl-2. 4. The piperine significantly enhanced the oral absorption of Linarin in rats by inhibiting P-glycoprotein mediated cellular efflux during the intestinal absorption and likely simultaneously by inhibiting the metabolism of Linarin.

Manghaslin (Quercetin 3-O-rutinoside-(1->2)-O-rhamnoside) has considerable α-glucosidase inhibitory activity, illustrating the anti-diabetic potential of phenolic-rich litchi pulp extracts. Manghaslin also shows inhibitory activity against AChE

Sinapine Thiocyanate, is a derivative of Sinapine (S486605), an alkaloidal amine found in black mustard seeds. It is the choline ester of Sinapic Acid (S486800). It is also a phenolic-chloine conjugates, acting as anti-oxidants and acetylcholinesterase inhibitors, that can be used for the treatment of Alzheimer's disease (AD).

Imperatorin (8-Isopentenyloxypsoralene) is a modulator of p38, ERK pathway. Imperatorin increases BMP-2 expression (mRNA) and increases bone density volume and mineralization in vivo.

Rivastigmine (Exelon) is a Cholinesterase Inhibitor, used for therapy of Alzheimer disease.

1. Corydaline (Corydalin), an isoquinoline alkaloid, is one of the major active constituents in a new prokinetic botanical agent. 2. Corydaline promotes gastric emptying and small intestinal transit and facilitates gastric accommodation. 3. Corydaline exhibits the anti-acetylcholinesterase, antiallergic, and antinociceptive activities. 4. Corydaline has potent inhibition of CYP2C19 and CYP2C9.

Polygalacic acid (Virgaureagenin G) is a triterpenoid isolated from the root of Polygala tenuifolia Willd that inhibits MMP expression. Polygalacic acid (Virgaureagenin G) can significantly improve the responsiveness of the cholinergic system, such as decreased acetylcholinesterase (AChE) activity, increased choline acetyltransferase (ChAT) activity, and increased acetylcholine (ACh) levels in the hippocampus and frontal cortex. Polygalacic acid (Virgaureagenin G) can also inhibit IL-1β-induced Wnt β-catenin activation and mitogen-activated protein kinase (MAPK) signaling pathways in chondrocytes, and is used in osteoarthritis (OA) related research.

Scopoletin (Esculetin 6-methyl ether) is a plant growth factor derived from the root of Scopolia carniolica, inhibits of acetylcholinesterase (AChE).

Ladostigil (Ladostigil free base) is an orally active dual inhibitor of cholinesterase and brain-selective monoamine oxidase (MAO) with inhibitory effects on MAO-B and AChE, with IC50 values of 37.1 and 31.8 μM, respectively.Ladostigil possesses anti-inflammatory, antioxidant, and neuroprotective activities, and may be used in studies of depression and Alzheimer's disease.

Diazinon (Dimpylate) is a thiophosphoric acid ester, functioning as a nonsystemic organophosphate insecticide that effectively targets and controls a variety of pests including cockroaches, silverfish, ants, and fleas.