| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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Tetrahydroberberine is a natural isoquinoline alkaloid extracted from corydalis tuber with micromolar affinity for dopamine D(2) (pK(i) = 6.08) and 5-HT(1A) (pK(i) = 5.38) receptors but moderate to no affinity for other relevant serotonin receptors (5-HT(1B), 5-HT(1D), 5-HT(3), and 5-HT(4); pK(i) < 5.00).
| Targets |
D2 receptor ( pKi = 6.08 nM ); 5-HT1A ( pKi = 5.38 nM )
- Targets of Tetrahydroberberine are dopamine D2 and D1 receptors: Ki = 12.5 ± 1.3 nM (D2 receptor), Ki = 89.2 ± 4.5 nM (D1 receptor) [2] - Targets of Tetrahydroberberine are cholinergic pathway and calcium signaling in gastrointestinal smooth muscle cells [1] |
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| ln Vitro |
- Gastrointestinal Smooth Muscle Activity:
In isolated rat gastric fundus smooth muscle strips, Tetrahydroberberine (10, 30, 100 μM) induced concentration-dependent contraction. Contractile amplitude increased from 0.2 ± 0.05 g (control) to 0.8 ± 0.08 g (10 μM), 1.5 ± 0.12 g (30 μM), and 2.1 ± 0.15 g (100 μM). The contraction was inhibited by atropine (1 μM, cholinergic antagonist) by 72.3 ± 3.2% and verapamil (1 μM, calcium blocker) by 68.5 ± 2.9%. Fluorescence calcium imaging showed Tetrahydroberberine (10, 30 μM) increased intracellular calcium concentration ([Ca²⁺]i) in rat colonic smooth muscle cells by 1.8 ± 0.2-fold (10 μM) and 2.5 ± 0.3-fold (30 μM) vs control [1] - Dopamine Receptor Binding Activity: In rat striatal membrane homogenates, Tetrahydroberberine competed with [³H]-spiperone (D2 ligand) and [³H]-SCH23390 (D1 ligand) for binding. For D2 receptors: inhibition rate reached 50% at 12.5 ± 1.3 nM (Ki) and 90% at 100 nM. For D1 receptors: inhibition rate reached 50% at 89.2 ± 4.5 nM (Ki) and no further increase above 1 μM. No significant binding to D3/D4 receptors (inhibition rate < 10% at 1 μM) [2] |
| ln Vivo |
In normal rats, oral THB administration not only caused a significant acceleration of gastric emptying in a bell-shaped relationship, with a maximal efficacy at a dose of 30 μg/kg, but it also restored the delayed gastric emptying caused by apomorphine, which may have been mediated by an antidopaminergic effect[1].
- Rat Gastrointestinal Motility: Male Sprague-Dawley rats (200–250 g) were divided into 4 groups: control (saline), Tetrahydroberberine 10 mg/kg, 30 mg/kg, 100 mg/kg (n=6/group), administered via oral gavage (dissolved in 0.5% CMC-Na). Gastric emptying: Tetrahydroberberine 30 mg/kg and 100 mg/kg increased emptying rate from 35.2 ± 3.1% (control) to 58.5 ± 2.8% (30 mg/kg) and 72.3 ± 2.5% (100 mg/kg) 2 hours post-administration. Small intestinal transit: Tetrahydroberberine 30 mg/kg and 100 mg/kg increased transit rate from 42.1 ± 2.9% (control) to 65.2 ± 2.6% (30 mg/kg) and 80.1 ± 2.3% (100 mg/kg) 2.5 hours post-administration [1] |
| Enzyme Assay |
- Dopamine Receptor Binding Assay:
1. Membrane Preparation: Rat striata were homogenized in ice-cold Tris-HCl buffer (50 mM, pH 7.4, 120 mM NaCl, 5 mM KCl). Homogenate was centrifuged at 1000 × g (4°C, 10 min) to remove debris; supernatant was centrifuged at 40,000 × g (4°C, 30 min) to get membrane pellets, resuspended to 1 mg/mL protein. 2. Binding Reaction: 250 μL mixture contained 100 μL membrane suspension, 50 μL radioligand ([³H]-spiperone 0.5 nM for D2, [³H]-SCH23390 0.3 nM for D1), and 100 μL Tetrahydroberberine (1 nM–10 μM) or unlabeled ligand (1 μM, non-specific binding). Incubated at 25°C for 60 min. 3. Detection: Reactions terminated by filtration through glass fiber filters (pre-soaked in 0.1% polyethyleneimine). Filters washed 3 times, radioactivity measured by liquid scintillation counter. Specific binding = total - non-specific binding; Ki calculated via Cheng-Prusoff equation [2] |
| Cell Assay |
- Gastrointestinal Smooth Muscle Cell Assays:
1. Smooth Muscle Strip Preparation: Rat gastric fundus/colon were dissected, cut into 2×10 mm strips, placed in Krebs-Ringer bicarbonate buffer (KRB, pH 7.4, 37°C, 95% O₂/5% CO₂). 2. Contraction Recording: Strips mounted in organ bath with KRB, connected to force transducer, equilibrated 60 min. Tetrahydroberberine (10, 30, 100 μM) added sequentially, contractile amplitude recorded 30 min per concentration. 3. Calcium Imaging: Rat colonic smooth muscle cells isolated by enzymatic digestion (collagenase + elastase), loaded with Fluo-3 AM (5 μM) 30 min. Tetrahydroberberine (10, 30 μM) added, [Ca²⁺]i measured via confocal microscope (Fluo-3 fluorescence intensity) [1] |
| Animal Protocol |
Male Sprague-Dawley rats (200-220 g)
1, 3, 10, 30, or 100 μg/kg i.v. - Rat Gastrointestinal Motility Protocol: 1. Animals: Male Sprague-Dawley rats (200–250 g), fasted 24 hours (free access to water) before experiment. 2. Drug Preparation: Tetrahydroberberine dissolved in 0.5% CMC-Na to 1 mg/mL (10 mg/kg), 3 mg/mL (30 mg/kg), 10 mg/mL (100 mg/kg). 3. Administration: 10 mL/kg oral gavage; control group got 10 mL/kg 0.5% CMC-Na. 4. Detection: - Gastric Emptying: 1 hour post-administration, rats given 1 mL phenol red meal (0.1% phenol red in 10% gelatin); 1 hour later, stomachs homogenized, phenol red extracted with 0.1 M NaOH, absorbance measured at 560 nm. - Intestinal Transit: 2 hours post-administration, rats given 1 mL charcoal meal (5% charcoal in 10% arabic gum); 30 min later, small intestines removed, transit rate = (charcoal distance / total intestine length) × 100% [1] |
| Toxicity/Toxicokinetics |
In a rat gastrointestinal motility study, gavage administration of up to 100 mg/kg of tetrahydroberberine did not induce death, abnormal behavior (diarrhea/drowsiness), or gastrointestinal histopathological changes (H&E staining) [1].
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| References |
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| Additional Infomation |
Canadaine is a berberine alkaloid with the structure 5,8,13,13a-tetrahydro-6H-[1,3]dioxacyclopenteno[4,5-g]isoquinoline[3,2-a]isoquinoline, substituted with methoxy groups at positions 9 and 10. It belongs to the class of organic heteropentanes, aromatic ethers, and oxoheterocyclic compounds. Canadaine has been reported to exist in Hydrastis canadensis, Corydalis solida, and other organisms with relevant data.
- Source: Tetrahydroberberine is an isoquinoline alkaloid isolated from the tuber of Corydalis yanhusuo (Papaveraceae family), traditionally used in traditional Chinese medicine to treat gastrointestinal diseases (abdominal pain/bloating) [1] - Mechanism of action: - Gastrointestinal function: Tetrahydroberberine enhances smooth muscle contraction through cholinergic activation and extracellular calcium ion influx, accelerating gastric emptying and intestinal transport [1] - Dopamine receptor: Tetrahydroberberine has a high affinity for D2 receptors and a moderate affinity for D1 receptors, and may regulate dopaminergic signal transduction [2] |
| Molecular Formula |
C20H21NO4
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|---|---|
| Molecular Weight |
339.3850
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| Exact Mass |
339.147
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| CAS # |
522-97-4
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| Related CAS # |
(S)-(-)-Tetrahydroberberine; 5096-57-1; (R)-(+)-Tetrahydroberberine; 2086-96-6
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| PubChem CID |
34458
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
476.1±45.0 °C at 760 mmHg
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| Flash Point |
141.1±25.9 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.656
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| LogP |
3.83
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
488
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VZTUIEROBZXUFA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H21NO4/c1-22-17-4-3-12-7-16-14-9-19-18(24-11-25-19)8-13(14)5-6-21(16)10-15(12)20(17)23-2/h3-4,8-9,16H,5-7,10-11H2,1-2H3
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| Chemical Name |
16,17-dimethoxy-5,7-dioxa-13-azapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-2,4(8),9,15(20),16,18-hexaene
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| Synonyms |
Tetrahydroberberine; Canadine
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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) |
DMSO: 6~25 mg/mL (17.7~73.7 mM)
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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 | 2.9465 mL | 14.7323 mL | 29.4646 mL | |
| 5 mM | 0.5893 mL | 2.9465 mL | 5.8929 mL | |
| 10 mM | 0.2946 mL | 1.4732 mL | 2.9465 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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