| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Natural alkaloid from Sceletium tortuosum; The primary targets of mesembrenone are the serotonin transporter (SERT) and phosphodiesterase 4 (PDE4) . By inhibiting SERT, mesembrenone prevents the reuptake of serotonin from the synaptic cleft, thereby increasing extracellular serotonin concentrations and enhancing serotonergic neurotransmission. Additionally, it inhibits PDE4, an enzyme responsible for the degradation of the intracellular second messenger cAMP; PDE4 inhibition leads to elevated cAMP levels, subsequently activating PKA and downstream transcription factors such as CREB. This dual modulation of two distinct signaling pathways is a unique pharmacological feature that distinguishes this compound from conventional SSRI antidepressants.
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| ln Vitro |
Continuing our systematic investigation on the Iberian Narcissus plants, we haveanalyzed Narcissus pallidulus Graells (Amaryllidaceae). Even though there have beensome efforts aimed to regard this species in a separate genus, at present it is included inthe section Ganymedes, a primitive group in the Narcissus L. genus (2). No phytochem-ical analysis has been reported on this plant. In the present communication we reportthe isolation and structure elucidation of mesembrenone [1], an alkaloid belonging tothe mesembrine group. Although both amaryllidaceous and mesembrine-type al-kaloids have common biogenetic precursors, further studies have demonstrated that thebiosyntheses of these two classes of alkaloids are fundamentally different (3). The pres-ence of mesembrenone in N. pallidulus is of chemotaxonomic interest because mesem-brines seem to be restricted to Aizoaceae-Mesembryanthemoideae (Dicotyledones) (4).Only twice before has the occurrence of mesembrane-type alkaloids in this plant family,namely amisine from Hymenocallis arenicola (5) and mesembrenol from Crinum oligan-thum (6), been reported. Some doubts were cast on this finding because of its unexpect-edness (7). However, our present communication gives support to the sporadic pres-ence in the Amaryllidaceae of such alkaloids as those found in some Sceletium (Aizoaceae)species [1].
In vitro studies have demonstrated that mesembrenone exhibits significant inhibitory activity against both the serotonin transporter (SERT) and phosphodiesterase 4 (PDE4). In SERT binding assays, it has an inhibition constant (Ki) of 27 nM and an IC₅₀ of less than 1 μM. For PDE4 inhibition, the Ki is 470 nM with an IC₅₀ of approximately 7.5 μM. Compared to mesembrine, another major alkaloid from the same plant which has a Ki of 1.4 nM for SERT, mesembrenone shows slightly weaker SERT affinity but more pronounced PDE4 inhibitory activity. Furthermore, in ex vivo electrophysiological experiments using brain slices, mesembrenone attenuates the amplitude of population spikes induced by electrical stimulation, suggesting a modulatory effect on neuronal excitability. |
| ln Vivo |
In zebrafish larvae models, mesembrenone exhibits clear anxiolytic-like effects. Under alternating light-dark stress conditions, mesembrenone-treated larvae show a significant increase in the percentage of time spent in the central arena (indicating reduced anxiety levels), with efficacy superior to other alkaloids tested in the same experiment. This effect is consistent with in silico predictions of high-affinity SERT binding. Furthermore, following one week of oral administration (5-10 mg/kg) of the standardized extract Zembrin® to rats, ex vivo hippocampal slice electrophysiological recordings demonstrate significantly attenuated population spike amplitudes, further validating its in vivo neuroactivity.
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| Enzyme Assay |
The SERT binding affinity of mesembrenone is typically determined using radioligand competitive binding assays. The brief protocol is as follows: Prepare membrane homogenates from cells expressing human SERT, incubate with serial dilutions of mesembrenone (typically ranging from 0.1 nM to 10 μM) and a fixed concentration of a radiolabeled ligand (e.g., [³H]imipramine or [³H]citalopram) at room temperature for 60-120 minutes. After incubation, separate bound and free radioligands by rapid vacuum filtration through GF/B glass fiber filters, wash the filters, and measure radioactivity using a scintillation counter. Generate competition curves by nonlinear regression analysis to calculate IC₅₀, then convert to Ki values using the Cheng-Prusoff equation. PDE4 activity assays employ fluorescence polarization or scintillation proximity assays using labeled cAMP as substrate to measure the compound's inhibitory effect on PDE4 hydrolytic activity.
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| Cell Assay |
The cellular-level activity of mesembrenone can be assessed by measuring its inhibitory effect on serotonin reuptake. A standard protocol is as follows: Culture cells stably expressing human SERT (e.g., HEK293-hSERT cells), seed at 5×10⁴ cells per well in 96-well plates, and culture for 24 hours. Remove the culture medium, add reaction buffer containing serial dilutions of mesembrenone (0.1 nM - 10 μM, prepared from DMSO stock in HBSS buffer) and a fixed concentration of [³H]serotonin, and incubate at 37°C for 10-20 minutes. After incubation, rapidly aspirate the reaction buffer and wash cells 2-3 times with ice-cold PBS to remove extracellular radioactivity. Add lysis buffer to lyse cells and measure intracellular radioactivity using a scintillation counter. Calculate the IC₅₀ for inhibition of serotonin reuptake to evaluate cellular-level activity. Cytotoxicity can be assessed in parallel using MTT or CCK-8 assays.
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| Animal Protocol |
The in vivo pharmacodynamics of mesembrenone can be evaluated using a zebrafish anxiety model. The specific protocol is as follows: Use 5-days post-fertilization (5-dpf) zebrafish larvae, placed individually in 96-well plates (one larva per well). Set up blank control, vehicle control, and mesembrenone treatment groups at various concentrations (range 0.1-100 μM). Pre-treat for 1-3 hours in a light-controlled incubator. Subsequently, transfer the zebrafish to a behavioral analysis chamber and subject them to alternating light (5 minutes) and dark (5 minutes) stimulation cycles. Record larval locomotion trajectories using a video tracking system. Primary evaluation metrics include: percentage of time spent in the central arena (reflecting anxiety levels, thigmotaxis behavior) and total distance moved (reflecting locomotor activity). Evaluate anxiolytic-like effects by comparing behavioral differences between treatment and control groups during the dark phase.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies indicate that mesembrenone has poor oral bioavailability. A pharmacokinetic study in mice following intravenous administration showed that the compound could be quantitatively detected in plasma after IV administration, but plasma levels were below the detection limit (10 ng/mL) after oral administration, suggesting significant first-pass metabolism leading to rapid metabolic clearance after oral absorption. Distribution concentrations in target tissues (e.g., brain) remain to be further investigated. In vitro permeability studies demonstrate that mesembrenone can permeate across intestinal, buccal, and sublingual mucosal tissues, with intestinal permeability lower than the high-permeability reference compound caffeine but significantly higher than the low-permeability reference compound atenolol. Metabolism studies reveal that the primary metabolic pathways include O-demethylation, N-demethylation, dihydroxylation, and hydroxylation, with phenolic metabolites partially excreted as glucuronide and sulfate conjugates in urine.
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| Toxicity/Toxicokinetics |
Cytotoxicity assessments in mammalian cell lines have shown no obvious cytotoxic effects of mesembrenone within its active concentration range. According to supplier-provided Safety Data Sheets (SDS), this compound is not currently classified as a hazardous substance and has not been listed as a carcinogen by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), or OSHA. However, due to the recreational use of this compound as a "legal herb," its metabolites can be detected in urine, but the toxicological effects of long-term use have not been adequately studied. This compound is for research use only and is not intended for human or veterinary use.
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| References | |
| Additional Infomation |
Mesembrenone belongs to the pyrrolidine class of compounds. It has been reported to exist in Bergeranthus scapiger, Lampranthus blandus, and other organisms with relevant data. Alkaloid separation—Fresh plant material (2.35 kg) was completely extracted with ethanol at room temperature. The ethanol extract was filtered, concentrated under reduced pressure, and then acidified to a concentration of 5% with acetic acid. The filtered acidic solution was washed with ether to remove neutral substances and extracted with chloroform. The alkaloid content detected in the chloroform phase was extremely low, making chemical characterization impossible. The acidic aqueous solution was alkalized to pH 8-9 with carbon dioxide and the alkaloids were extracted with chloroform. The chloroform phase was then washed with carbon dioxide solution to remove the solvent, yielding an alkaloid residue (2485 mg). The crude alkaloid extract was separated by silica gel column chromatography (170 g). Elution with an ethyl acetate-ethanol (10:2) solution of gradually increasing polarity yielded amorphous alkaloids, which were further purified by preparative crystallization. After being dissolved in ethanol, the residue was treated with picric acid and crystallized in methanol/acetone to obtain 73.7 mg of crystals [1].
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| Molecular Formula |
C17H21NO3
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|---|---|
| Molecular Weight |
287.354
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| Exact Mass |
287.152
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| Elemental Analysis |
C, 71.06; H, 7.37; N, 4.87; O, 16.70
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| CAS # |
468-54-2
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| PubChem CID |
216272
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
383.9±42.0 °C at 760 mmHg
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| Flash Point |
186.0±27.9 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.563
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| Source |
Bergeranthus scapiger, Lampranthus blandus
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| LogP |
1.37
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
436
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CN1CC[C@@]2(C=CC(=O)C[C@@H]21)C3=CC(=C(C=C3)OC)OC
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| InChi Key |
HDNHBCSWFYFPAN-IRXDYDNUSA-N
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| InChi Code |
InChI=1S/C17H21NO3/c1-18-9-8-17(7-6-13(19)11-16(17)18)12-4-5-14(20-2)15(10-12)21-3/h4-7,10,16H,8-9,11H2,1-3H3/t16-,17-/m0/s1
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| Chemical Name |
(3aR,7aS)-3a-(3,4-dimethoxyphenyl)-1-methyl-2,3,7,7a-tetrahydroindol-6-one
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| Synonyms |
Mesembrenone; 468-54-2; (+)-Mesembrenone; Mesembrenone, (+)-; (3aR,7aS)-3a-(3,4-dimethoxyphenyl)-1-methyl-2,3,7,7a-tetrahydroindol-6-one; HT8JNS8E79; CHEMBL4781238;
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4801 mL | 17.4004 mL | 34.8008 mL | |
| 5 mM | 0.6960 mL | 3.4801 mL | 6.9602 mL | |
| 10 mM | 0.3480 mL | 1.7400 mL | 3.4801 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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