| Size | Price | Stock | Qty |
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| 10mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
- (+)-Kavain potentiates the activity of γ-aminobutyric acid type A (GABAA) receptors, with no specific IC50, Ki, or EC50 values reported. It shows higher potentiation effect on GABAA receptors containing the α1 subunit compared to those with α2 or α3 subunits [2]
- (+)-Kavain affects the levels of neurotransmitters including dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in striatal and cortical brain regions. [3] - (+)-Kavain inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) production via the extracellular signal-regulated kinase (ERK)/lipopolysaccharide-induced TNF-α factor (LITAF) signaling pathway. [4] |
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| ln Vitro |
(+)-Kavain (10-300 μM) increases in a concentration-dependent manner the reactions evoked by GABA. At 300 μM, Kavain's modulatory action was only moderately enhanced, measuring at 170±23% [2]. Through its inhibition of LITAF, (+)-Kavain prevents cells from secreting TNF-α [4].
- In human embryonic kidney (HEK) 293 cells transfected with different GABAA receptor subunit combinations (α1β2γ2, α2β2γ2, α3β2γ2), application of (+)-Kavain (10 μM) significantly increased the peak amplitude of GABAA receptor-mediated currents induced by a submaximal concentration of GABA (3 μM). The potentiation effect was most prominent on α1β2γ2 receptors, followed by α2β2γ2, and weakest on α3β2γ2 receptors. Additionally, (+)-Kavain (1–30 μM) shifted the GABA concentration-response curve to the left without changing the maximum response, indicating a positive allosteric modulatory effect [2] - In murine macrophage RAW264.7 cells stimulated with LPS (1 μg/mL), pretreatment with (+)-Kavain (10, 20, 40 μM) for 1 h dose-dependently reduced the secretion of TNF-α. At 40 μM, (+)-Kavain inhibited TNF-α production by approximately 50%. Western blot analysis showed that (+)-Kavain (20, 40 μM) decreased LPS-induced phosphorylation of ERK1/2 and downregulated the protein expression of LITAF in a dose-dependent manner [4] |
| ln Vivo |
- Male Wistar rats were administered (+)-Kavain at a dose of 30 mg/kg via intraperitoneal injection. At 30, 60, and 120 minutes after administration, the rats were sacrificed, and striatal and cortical brain regions were dissected. High-performance liquid chromatography (HPLC) analysis revealed that in the striatum, (+)-Kavain significantly increased DA levels at 30 minutes (by approximately 20%) and 60 minutes (by approximately 15%) compared to the control group, while DOPAC levels were decreased by approximately 10% at 60 minutes. In the cortex, (+)-Kavain increased 5-HT levels by approximately 18% at 30 minutes, and 5-HIAA levels were unchanged at all time points [3]
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| Enzyme Assay |
- For GABAA receptor function assay: HEK 293 cells were transfected with plasmids encoding GABAA receptor subunits (α1β2γ2, α2β2γ2, or α3β2γ2) using a standard transfection reagent. After 24–48 hours of transfection, whole-cell patch-clamp recordings were performed at room temperature. The extracellular solution contained specific concentrations of NaCl, KCl, CaCl2, MgCl2, and HEPES (pH 7.4). GABA and (+)-Kavain were applied via a fast perfusion system. The currents induced by GABA (3 μM, submaximal concentration) were recorded before and after application of (+)-Kavain (1–30 μM). The peak current amplitudes were measured, and the potentiation ratio was calculated as (current with (+)-Kavain - current with GABA alone) / current with GABA alone × 100% [2]
- For ERK phosphorylation and LITAF expression assay: RAW264.7 cells were seeded in 6-well plates and cultured until confluence. The cells were pretreated with (+)-Kavain (20, 40 μM) for 1 h, then stimulated with LPS (1 μg/mL) for 30 minutes (for ERK phosphorylation) or 6 hours (for LITAF expression). After treatment, the cells were lysed with a lysis buffer containing protease and phosphatase inhibitors. The protein concentration in the cell lysate was determined using a protein assay kit. Equal amounts of protein (30 μg per lane) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to a polyvinylidene difluoride (PVDF) membrane. The membrane was blocked with 5% non-fat milk for 1 h at room temperature, then incubated with primary antibodies against phosphorylated ERK1/2 (p-ERK1/2), total ERK1/2 (t-ERK1/2), LITAF, or β-actin (internal control) overnight at 4°C. After washing with TBST buffer, the membrane was incubated with a horseradish peroxidase (HRP)-conjugated secondary antibody for 1 h at room temperature. The protein bands were visualized using an enhanced chemiluminescence (ECL) detection system, and the band intensity was quantified using image analysis software [4] |
| Cell Assay |
- For TNF-α secretion assay in RAW264.7 cells: RAW264.7 cells were seeded in 96-well plates at a density of 5×104 cells per well and cultured overnight. The cells were pretreated with different concentrations of (+)-Kavain (10, 20, 40 μM) for 1 h, then stimulated with LPS (1 μg/mL) for 24 hours. After incubation, the cell culture supernatant was collected, and the concentration of TNF-α was measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's protocol. The absorbance at 450 nm was read using a microplate reader, and the concentration of TNF-α was calculated based on a standard curve [4]
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| Animal Protocol |
- For neurotransmitter level detection in rats: Male Wistar rats (weighing 200–250 g) were randomly divided into control group and (+)-Kavain treatment group. (+)-Kavain was dissolved in a mixture of dimethyl sulfoxide (DMSO) and physiological saline (DMSO final concentration < 5%), and administered to rats via intraperitoneal injection at a dose of 30 mg/kg. The control group received the same volume of vehicle (DMSO/physiological saline mixture). At 30, 60, and 120 minutes after administration, the rats were anesthetized with an anesthetic agent and sacrificed by decapitation. The brain was quickly removed, and the striatum and cortex were dissected on an ice-cold plate. The dissected brain regions were homogenized in a cold perchloric acid solution (0.1 M) containing EDTA. The homogenate was centrifuged at 12,000 × g for 15 minutes at 4°C, and the supernatant was collected and filtered through a 0.22 μm filter. The concentrations of DA, DOPAC, 5-HT, and 5-HIAA in the supernatant were determined using HPLC with electrochemical detection [3]
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| References | |
| Additional Infomation |
Kawain belongs to the 2-pyranone class of compounds and is an aromatic ether.
Kawain has been reported to be found in plants of the Piper genus (such as black pepper, kava, and Siberian alder), and there is relevant data. See also: Kava root (part). - (+)-Kawain is one of the main active ingredients of kava (Piper methysticum) extract, which has traditionally been used to treat anxiety disorders [2, 3, 4]. - (+)-Kawain enhances GABAA receptors and is considered to be one of the mechanisms by which kava extract exerts its anti-anxiety effect [2]. - (+)-Kawain modulates neurotransmitter (DA, 5-HT) levels in the brain, which may contribute to its central nervous system effects in addition to its anti-anxiety effects [3]. - Inhibition of (+)-Kawain inhibits LPS-induced TNF-α production, suggesting that the compound may have anti-inflammatory effects [4]. |
| Molecular Formula |
C14H14O3
|
|---|---|
| Molecular Weight |
230.2592
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| Exact Mass |
230.094
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| CAS # |
500-64-1
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| PubChem CID |
5281565
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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 |
432.6±45.0 °C at 760 mmHg
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| Melting Point |
142-148ºC
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| Flash Point |
184.6±23.3 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.565
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| LogP |
1.69
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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 |
3
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| Heavy Atom Count |
17
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| Complexity |
324
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| Defined Atom Stereocenter Count |
1
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| SMILES |
COC1=CC(=O)O[C@H](C1)/C=C/C2=CC=CC=C2
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| InChi Key |
XEAQIWGXBXCYFX-GUOLPTJISA-N
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| InChi Code |
InChI=1S/C14H14O3/c1-16-13-9-12(17-14(15)10-13)8-7-11-5-3-2-4-6-11/h2-8,10,12H,9H2,1H3/b8-7+/t12-/m0/s1
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| Chemical Name |
(2R)-4-methoxy-2-[(E)-2-phenylethenyl]-2,3-dihydropyran-6-one
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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 : ~50 mg/mL (~217.15 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (9.03 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.08 mg/mL (9.03 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 20.8 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: ≥ 2.08 mg/mL (9.03 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 | 4.3429 mL | 21.7146 mL | 43.4292 mL | |
| 5 mM | 0.8686 mL | 4.3429 mL | 8.6858 mL | |
| 10 mM | 0.4343 mL | 2.1715 mL | 4.3429 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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