| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
Cytochrome P450 enzymes (CYP) – Tetrahydropiperine inhibits constitutive AHH (IC50 = 23 μM) and shows no inhibition (NI) of 3-methylcholanthrene (3MC)-inducible AHH [2].
For MOCD: inhibits constitutive MOCD (IC50 = 25 μM) and PB-inducible MOCD (IC50 = 27 μM) [2]. Kinetic analysis of MOCD demethylation: Tetrahydropiperine acts as a non-competitive inhibitor with Ki = 35 μM [2]. |
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| ln Vitro |
In rat hepatic microsomes from untreated rats, Tetrahydropiperine (14) inhibited constitutive AHH activity in a concentration-dependent manner: at 10 μM, 49.6 ± 3.4 pmol/min/mg protein; at 30 μM, 18.2 ± 2.4; at 100 μM, 7.41 ± 0.42; IC50 = 23 μM. In contrast, it showed no inhibition of 3MC-inducible AHH activity (at 10, 30, 100 μM, activities were 492±54, 540±45, 490±39 pmol/min/mg protein respectively, IC50 = NI) [2].
For MOCD activity in untreated rat microsomes, Tetrahydropiperine inhibited constitutively: at 10 μM, 303±21; at 30 μM, 132±12; at 100 μM, 109±11 pmol/min/mg protein; IC50 = 25 μM. For PB-inducible MOCD: at 10 μM, 796±68; at 30 μM, 503±41; at 100 μM, 367±33 pmol/min/mg protein; IC50 = 27 μM [2]. In rat Reuber hepatoma H4IIEC3/G- cells exposed for 4 hours to 50 μM Tetrahydropiperine, AHH activity in control cells was 2.8±1.0 pmol/min/mg protein (compared to DMSO control 68.4±2.3), and in BA-treated cells was 63±6 (compared to BA control 75±4). MOCD activity in control cells was 7.0±0.1 (DMSO control 16.5±1.5) and in PB-treated cells was 7.5±1.5 (DMSO control 13.5±3.0) [2]. Long-term exposure (27 hours, 60 μM) of H4IIEC3/G- cells to Tetrahydropiperine induced AHH activity by about 70% (similar to piperine), while MOCD activity continued to show marginal impairment [2]. Kinetic analysis showed that Tetrahydropiperine non-competitively inhibited MOCD demethylation in untreated rat liver microsomes, with Ki = 35 μM and Km remained similar (150 μM) [2]. |
| ln Vivo |
In male Swiss albino mice, intraperitoneal administration of Tetrahydropiperine (5 mg/kg body weight) 30 minutes before hexobarbital (60 mg/kg, ip) potentiated hexobarbital-induced sleeping time compared to piperine [2].
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| Enzyme Assay |
Aryl hydrocarbon hydroxylase (AHH) activity was measured in rat liver microsomes. The reaction mixture (1 mL total volume) contained 50 mM Tris-HCl buffer pH 7.6, 3 mM MgCl2, 0.6 mM NADPH, 0.5 to 2.5 mg microsomal protein, and Tetrahydropiperine or test compound dissolved in 10 μL of 50% methanol. The reaction was initiated under subdued light with 0.1 mM benzo(a)pyrene in 20 μL of 50% methanol and incubated at 37°C for 30 min in a shaking water bath. The reaction was terminated and the relative fluorescence of the aqueous phase was measured at 396 nm excitation and 520 nm emission using 3-OH-benzo(a)pyrene as reference standard [2].
7-Methoxycoumarin O-demethylase (MOCD) activity was assayed in rat liver microsomes. The assay system (1 mL total volume) contained 40 mM Tris-HCl buffer pH 7.6, 5 mM MgCl2, 0.25 mg NADPH, 0.1-0.2 mg microsomal protein, and Tetrahydropiperine or test compound in 10 μL of 50% methanol. The reaction was started with 0.4 mM 7-methoxycoumarin in 10 μL of 50% methanol and incubated for 10 min at 37°C in a constant shaking water bath. The reaction was terminated with 75 μL of 15% cold trichloroacetic acid (w/v). The product 7-hydroxycoumarin was extracted and measured fluorometrically at 396 nm excitation and 520 nm emission [2]. For kinetic analysis, microsomes from untreated rat liver were used. The MOCD activity was measured at various substrate concentrations in the presence and absence of Tetrahydropiperine (15, 30, 60 μM). Lineweaver-Burk double reciprocal and Dixon plots were used to determine Km, Vmax, and Ki values. All three analogues caused non-competitive inhibition; the apparent Km was approximately 150 μM, while Vmax decreased with increasing inhibitor concentrations [2]. |
| Cell Assay |
Rat Reuber hepatoma H4IIEC3/G- cells were seeded at a density of 1×10^6 cells per 90 mm plastic dishes in culture medium containing fetal calf serum and antibiotics and allowed to grow for 48 hours. For short-term exposure, cultures were incubated for 4 hours with medium containing 50 μM Tetrahydropiperine (delivered in 15 μL DMSO). For long-term exposure, cultures were treated for 27 hours with 60 μM Tetrahydropiperine. Control plates received only the vehicle (DMSO). In experiments with inducers, cultures were pretreated with 20 μM benzo(a)anthracene (BA) for 18 hours or 2 mM phenobarbital (PB) for 3 days, and the treatment with Tetrahydropiperine was started at the same time. After exposure, the medium was removed, cells were washed twice with phosphate-buffered saline (PBS), scraped, collected in PBS, and centrifuged. The cell pellet was stored in liquid nitrogen. Before enzyme assay, the pellet was suspended in 0.5 mL of 50 mM Tris-HCl pH 7.4. AHH and MOCD activities were then measured as described [2].
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| Animal Protocol |
Male Swiss albino mice (25±2 g body weight) were used. Tetrahydropiperine was administered intraperitoneally at a dose of 5 mg/kg body weight, 30 minutes before hexobarbital injection (60 mg/kg body weight, intraperitoneal). The control animals received only the vehicle. Hexobarbital-induced sleeping time was determined as the time required for the mice to regain their righting reflex [2].
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| References |
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| Additional Infomation |
Tetrahydropiperine is a member of the benzodioxane class of compounds. It has been reported to be found in black pepper (Piper swartzianum), nodular pepper (Piper tuberculatum), and long pepper (Piper longum), and relevant data are available for reference.
Tetrahydropiperine (compound 1) was isolated for the first time from a natural source, the fruits of Piper longum, collected from Andhra Pradesh, India in September 1997. The dried fruits were powdered and extracted with CH2Cl2-MeOH (1:1) for 120 h at room temperature, followed by column chromatography over silica gel. The structure was determined by NMR and MS and found identical to the product formed by hydrogenation of piperine in MeOH in the presence of Pd/C [1]. In structure-activity relationship studies, saturation of the conjugated double bonds of piperine (yielding Tetrahydropiperine) resulted in significantly enhanced inhibition of constitutive CYP activities while losing inhibitory effect on 3MC-inducible AHH. This suggests that the saturated side chain increases flexibility, allowing differential interaction with CYP isoforms [2]. |
| Molecular Formula |
C17H23NO3
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|---|---|
| Molecular Weight |
289.3694
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| Exact Mass |
289.167
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| Elemental Analysis |
C, 70.56; H, 8.01; N, 4.84; O, 16.59
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| CAS # |
23434-88-0
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| PubChem CID |
581676
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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 |
469.9±24.0 °C at 760 mmHg
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| Melting Point |
41ºC
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| Flash Point |
238.0±22.9 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.556
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| LogP |
3.67
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
21
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| Complexity |
341
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1C([H])=C([H])C2=C(C=1[H])OC([H])([H])O2)N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]
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| InChi Key |
APZYKUZPJCQGPP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H23NO3/c19-17(18-10-4-1-5-11-18)7-3-2-6-14-8-9-15-16(12-14)21-13-20-15/h8-9,12H,1-7,10-11,13H2
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| Chemical Name |
5-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylpentan-1-one
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| Synonyms |
THP; Tetrahydropiperine
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~100 mg/mL (~345.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.64 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4558 mL | 17.2789 mL | 34.5578 mL | |
| 5 mM | 0.6912 mL | 3.4558 mL | 6.9116 mL | |
| 10 mM | 0.3456 mL | 1.7279 mL | 3.4558 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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