| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: =96.73%
| Targets |
Natural alkaloid; acetylcholinesterase (AChE)
Acetylcholinesterase (AChE) (IC50 = 19,300 ± 1,742 nM against rat cortex AChE; IC50 = 228,000 ± 600 nM against rat serum butyrylcholinesterase; selectivity for AChE = 12) [2] |
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| ln Vitro |
A number of studies indicate that free radicals are involved in the neurodegeneration in Alzheimer's disease (AD). The present study was mainly conducted to examine the effect of Huperzine B on H(2)O(2) induced toxicity in rat pheochromocytoma line PC12 by measuring cell lesion, level of lipid peroxidation and antioxidant enzyme activities. Following a 30 min exposure of the cells to H(2)O(2) (150 microM), a marked decrease in cell survival, activities of glutathione peroxidase and catalase as well as increased production of malondialdehyde (MDA) were found. Pretreatment of the cells with huperzine B (10-100 microM) prior to H(2)O(2) exposure significantly elevated the cell survival, antioxidant enzyme activities and decreased the level of MDA. The above-mentioned neuroprotective effects are also observed with tacrine (1 microM), donepezil (10 microM) and galanthamine (10 microM), suggesting that the neuroprotective effects of cholinesterase inhibitor might partly contribute to the clinical efficacy in AD treatment[1].
In PC12 cells, pretreatment with Huperzine B (10–100 μM) for 2 h prior to 30 min exposure to 150 μM H2O2 significantly elevated cell survival, increased glutathione peroxidase and catalase activities, and decreased malondialdehyde level. The protective effects were concentration-dependent. [1] In PC12 cells, Huperzine B (0.1–100 μM) pretreatment markedly preserved cell viability against H2O2-induced injury as determined by MTT reduction and morphological observation. The H2O2 exposure (150 μM, 30 min) caused decreases in GSH-Px and catalase activities by 59% and 64% respectively, and increased MDA level by 51%; these changes were attenuated by Huperzine B (10–100 μM). [1] |
| Enzyme Assay |
Natural (-)-huperzine B (HupB), isolated from Chinese medicinal herb, displayed moderate inhibitory activity of acetylcholinesterase (AChE). Based on the active dual-site of AChE, a series of novel derivatives of bis- and bifunctional HupB were designed and synthesized. The AChE inhibition potency of most derivatives of HupB was enhanced about 2-3 orders of magnitude as compared with the parental HupB. Among bis-HupB derivatives, 12h exhibited the most potent in the AChE inhibition and has been evaluated for its pharmacological actions in vivo on ChE inhibition, cognitive enhancement, and neuroprotection. The docking study on the bis-HupB derivatives 12 series with TcAChE has demonstrated that the ligands bound to the dual-site of the enzyme in different level[2].
Acetylcholinesterase and butyrylcholinesterase activities were measured by a spectrophotometric method using acetylthiocholine iodide (2 mmol/mL) or butyrylthiocholine iodide (2 mmol/mL) as substrates. The reaction mixture containing substrate, sodium phosphate buffer (0.1 mmol/L, 1 mL), and enzyme source (rat cortex homogenate for AChE, rat serum for BuChE, 0.1 mL) was incubated in a total volume of 4 mL at 37°C for 8 min. The reaction was terminated by adding 3% SDS (1 mL), followed by 0.2% DTNB (1 mL) to produce the yellow anion of 5-thio-2-nitrobenzoic acid. The rate of color production was measured at 440 nm. Enzyme activity was expressed as percentage of control. IC50 was defined as the concentration of inhibitor producing 50% inhibition. [2] |
| Cell Assay |
PC12 cells were maintained at 37°C in a humidified atmosphere with 5% CO2. Cells were seeded into multiwell plates at 2×10^4 cells/mL in phenol red-free RPMI1640 medium supplemented with 10% heat-inactivated bovine calf serum, 100 U/mL penicillin, 100 μg/mL streptomycin, and 2 mM L-glutamine. Experiments were carried out 24–48 h after seeding. Huperzine B and other test compounds were dissolved and diluted with PBS. After 2 h pretreatment with test compounds, hydrogen peroxide (150 μM) was added to PC12 cell cultures for 30 min, then replaced with fresh medium. Assays for cell viability, lipid peroxidation, and antioxidant enzyme activities were performed 24 h after culturing in fresh medium. [1]
Cell survival was evaluated by morphological observation under phase-contrast microscope and by MTT reduction assay. For antioxidant enzyme and lipid peroxide assays, cultures were washed with ice-cold PBS, pooled in 0.5% Triton X-100 and 0.1 M PBS-0.05 mM EDTA buffer, and homogenized. The homogenate was centrifuged at 3000×g for 20 min at 4°C, and supernatants were used for assays. [1] Glutathione peroxidase activity was analyzed by Mills' procedure; one enzyme unit was defined as a decrease of 1 μM GSH per minute after subtracting non-enzymatic reaction. Catalase activity was measured by the rate of H2O2 consumption at 240 nm. Malondialdehyde content was determined by the thiobarbituric acid method. Protein level was measured by Coomassie blue protein-binding method using bovine serum as standard. [1] |
| Toxicity/Toxicokinetics |
Huperzine B has lower peripheral cholinergic side effects compared to tacrine. [1]
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| References |
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| Additional Infomation |
Huperzine A is a phenanthrene compound. Huperzine A is a novel acetylcholinesterase inhibitor. It has been reported to exist in Huperzine serpentina, Huperzine tricolor, and other organisms with relevant data. Drug Indications It is being investigated for the treatment of Alzheimer's disease. Mechanism of Action Huperzine A has been identified as an acetylcholinesterase inhibitor. This is the same mechanism of action as drugs used to treat Alzheimer's disease, such as galantamine and donepezil. Pharmacodynamics Huperzine A is an alkaloid derived from Huperzine serpentina (sold as a herbal product in the United States). It is being investigated as an acetylcholinesterase inhibitor. Clinical trials in China have shown that huperzine A is comparable in efficacy to currently available drugs and may be safer in terms of side effects.
Huperzine B contains a pyridone group, which may contribute to its protective effects against oxidative damage, as pyridone-containing compounds have been shown to prevent lipid peroxidation and decrease reactive oxygen species generation. [1] The chemical structure of Huperzine B has some similarity to Huperzine A, and the neuroprotective effects of cholinesterase inhibitors may partly contribute to their clinical efficacy in Alzheimer's disease treatment. [1] In Alzheimer's disease, free radicals are involved in neurodegeneration. Huperzine B was shown to protect against H2O2-induced toxicity by elevating antioxidant enzyme activities and reducing lipid peroxidation, suggesting its cytoprotective effect involves stimulation of cellular defense mechanisms against oxidative stress. [1] |
| Molecular Formula |
C16H20N2O
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|---|---|
| Molecular Weight |
256.3428
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| Exact Mass |
256.157
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| Elemental Analysis |
C, 74.97; H, 7.86; N, 10.93; O, 6.24
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| CAS # |
103548-82-9
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| PubChem CID |
5462442
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
533.5±50.0 °C at 760 mmHg
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| Flash Point |
216.4±30.3 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.624
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| LogP |
1.98
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
19
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| Complexity |
543
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| Defined Atom Stereocenter Count |
3
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| SMILES |
O=C1C([H])=C([H])C2=C(C([H])([H])[C@]3([H])C([H])=C(C([H])([H])[H])C([H])([H])[C@]42[C@]3([H])C([H])([H])C([H])([H])C([H])([H])N4[H])N1[H]
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| InChi Key |
YYWGABLTRMRUIT-HWWQOWPSSA-N
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| InChi Code |
InChI=1S/C16H20N2O/c1-10-7-11-8-14-13(4-5-15(19)18-14)16(9-10)12(11)3-2-6-17-16/h4-5,7,11-12,17H,2-3,6,8-9H2,1H3,(H,18,19)/t11-,12+,16+/m0/s1
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| Chemical Name |
(1R,9R,10R)-16-methyl-6,14-diazatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,16-trien-5-one
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| Synonyms |
Fordimine; Huperzine B; 103548-82-9; Fordimine; 1gpn; CHEMBL245079; Lycodin-1(18H)-one, 8,15-didehydro-; (-)-Huperzine B; (1R,9R,10R)-16-methyl-6,14-diazatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,16-trien-5-one; (–)-Huperzine B
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~97.53 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (3.90 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1 mg/mL (3.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9011 mL | 19.5053 mL | 39.0107 mL | |
| 5 mM | 0.7802 mL | 3.9011 mL | 7.8021 mL | |
| 10 mM | 0.3901 mL | 1.9505 mL | 3.9011 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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