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| Targets |
TRPV1
Transient receptor potential vanilloid 1 (TRPV1). Dihydrocapsiate is described as an orally active agonist of the TRPV1 ion channel. The TRPV1 receptor is a non-selective cation channel involved in pain sensation, thermoregulation, and metabolism. By activating TRPV1, Dihydrocapsiate can influence energy expenditure and glucose homeostasis, making it relevant for research into obesity and other metabolic disorders. |
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| ln Vitro |
Cell viability is unaffected by dihydrocapsiate (10, 25 and 50 μM; 48 hours; human preadipocytes)[1]. In contrast to increasing the expression levels of PGC1α (master regulator of mitochondrial biogenesis) and TBX1 (marker of "brite" cell), dihydrocapsiate (10 and 20 μM; 8 days; mature adipocytes) significantly reduces the expression levels of other adipogenic markers (such as SREBP1, FABP4, PLIN1, ADIPOQ, and LEPTIN) and inflammatory markers (MCP1 and TNFα) [1]. RAW 264.7 cells treated with dihydrocapsiate (25–200 μM) inhibits the release of NO and the production of intracellular ROS[1].
In vitro, Dihydrocapsiate acts as a TRPV1 agonist, activating the ion channel and leading to calcium influx in cultured cells. In cellular models, this activation is associated with the prevention of high-fat diet-induced adiposity and the improvement of insulin sensitivity. Detailed IC50 or EC50 values are not widely reported, but its activity is well-documented through the prevention of pathological features associated with metabolic syndrome. |
| ln Vivo |
Dihydrocapsiate (2 and 10 mg/kg; po) improves insulin levels, morphometric parameters, and the prevention of high-fat diet (HFD)-induced adipocyte size. It also prevents HFD-induced hepatic steatosis, prevents HFD-induced fat deposition, and enhances genes related to mitochondrial biogenesis in BAT. Lastly, it improves intestinal morphology and modifies the availability of saturated fat.
In vivo, oral administration of Dihydrocapsiate has been shown to effectively prevent high-fat diet-induced adiposity, hepatic steatosis, and glucose intolerance in mice. At doses of 2 and 10 mg/kg via oral administration, the compound improves morphometric parameters and insulin levels, indicating a beneficial effect on metabolic health. These effects are linked to its activity as an oral TRPV1 agonist. |
| Enzyme Assay |
Standard cell‑free binding assays for Dihydrocapsiate to TRPV1 receptors can be performed using membrane preparations from cells expressing the human TRPV1 channel. Membranes (20-30 ug protein) are incubated with a radiolabeled TRPV1 agonist such as [3H]Resiniferatoxin (RTX) (0.1-0.5 nM) in the presence of varying concentrations of Dihydrocapsiate in a 50 mM HEPES buffer (pH 7.4) containing 0.1% BSA. The reaction proceeds for 60-90 minutes at 22degC. Non‑specific binding is determined in the presence of 10 uM unlabeled RTX. Bound radioligand is separated by filtration through GF/B filters presoaked in 0.5% polyethyleneimine. The filters are washed and bound radioactivity is measured by liquid scintillation counting. The IC50 and Ki values are calculated from the resulting displacement curves.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: Human preadipocytes Tested Concentrations: 10, 25 and 50 μM Incubation Duration: 48 hrs (hours) Experimental Results: Did not affect cell viability . RT-PCR[1] Cell Types: Mature adipocytes Tested Concentrations: 10 and 20 μM Incubation Duration: 8 days Experimental Results: Markedly diminished the expression levels of other adipogenic markers (such as SREBP1, FABP4, PLIN1, ADIPOQ and LEPTIN) and inflammatory markers (MCP1 and TNFα), whereas it enhanced the expression levels of PGC1α (master regulator of mitochondrial biogenesis) and TBX1 (marker of “brite” cell). For cellular assays, HEK-293 cells stably expressing the human TRPV1 receptor are seeded in 96‑well plates (40,000 cells/well) and cultured for 48 hours. Cells are loaded with the calcium-sensitive dye Fluo-4 AM (2.5 uM) in HBSS buffer with 20 mM HEPES and 2.5 mM probenecid for 60 minutes at 37degC. Dihydrocapsiate is then added at concentrations ranging from 0.001 to 100 uM, and the resulting increase in intracellular calcium fluorescence is measured in real-time using a fluorescence plate reader. The EC50 value for receptor activation is determined from the concentration-response curve. Blockade by a specific TRPV1 antagonist (e.g., capsazepine) can be used to verify the specificity of the signal. |
| Animal Protocol |
Animal/Disease Models: HFD-fed mice[1]
Doses: 2 and 10 mg/kg Route of Administration: Po Experimental Results: Improved morphometric parameters and insulin levels, prevented HFD -induced adipocyte size and enhanced energy expenditure-related genes in WAT, alleviated HFD-induced hepatic steatosis, prevented HFD-induced fat deposition and enhanced mitochondrial biogenesis genes in BAT and improved intestinal morphology and modulates SCFA availability. In vivo efficacy studies for Dihydrocapsiate are typically performed in male C57BL/6 mice (8-10 weeks old, 20-25 g) fed a high-fat diet (HFD) to induce obesity and metabolic dysfunction. Dihydrocapsiate is formulated in a vehicle such as 0.5% methylcellulose or medium-chain triglyceride (MCT) oil and administered orally (10 mg/kg) once daily for a period of 8-12 weeks. Body weight, food intake, and fasting blood glucose levels are monitored weekly. At the end of the study, an oral glucose tolerance test (OGTT) is conducted to assess glucose clearance. Animals are euthanized, and serum is collected for insulin and lipid profile analysis. Tissues such as the liver, white adipose tissue (WAT), and brown adipose tissue (BAT) are collected, weighed, and processed for histological analysis (e.g., H&E staining of liver and WAT sections) to assess steatosis and adipocyte size. Gene expression analysis of metabolic markers (e.g., PPARgamma, UCP1) in adipose tissue by qPCR can also be performed. |
| ADME/Pharmacokinetics |
Dihydrocapsiate is an orally active compound, but detailed pharmacokinetic data are not widely published. In a rat study using a single oral gavage dose of 10 mg/kg of 14C-labeled Dihydrocapsiate, the compound was metabolized, likely by hydrolysis in the gut or by esterases in the blood. The metabolites were rapidly absorbed, reaching a maximal plasma concentration in 40 minutes, and then converted to conjugates in the liver, which were eliminated by the kidneys into urine. The apparent plasma half-life was found to be 2.4 hours. This indicates rapid absorption and a relatively short duration of action.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies indicate that Dihydrocapsiate has a low toxicological potential. In animal studies at the effective oral doses used for metabolic research (up to 10 mg/kg/day), no significant adverse effects have been reported. As a naturally occurring capsinoid, it is generally recognized as safe in the context of dietary consumption and typical research doses. No significant hepatotoxicity, nephrotoxicity, or genotoxicity has been observed in standard assays.
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| References | |
| Additional Infomation |
Dihydrocapsiate belongs to the methoxybenzene and phenolic compounds. Dihydrocapsiate is currently being studied in the clinical trial NCT00999297 (Effect of Dihydrocapsiate administration for 4 weeks on resting metabolic rate).
Dihydrocapsiate is a naturally occurring capsinoid and a dihydrocapsinoid analogue. As an orally active TRPV1 agonist, it is used primarily in research to study metabolic diseases. Its mechanism of action involves activating TRPV1 channels to influence energy balance and glucose homeostasis. Although it is an agonist of the pain-related TRPV1 receptor, it does not produce the pungent sensation associated with capsaicin. It has not been approved by the FDA for any therapeutic use. |
| Molecular Formula |
C18H28O4
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| Molecular Weight |
308.41
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| Exact Mass |
308.199
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| CAS # |
205687-03-2
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| PubChem CID |
9873754
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| Appearance |
Colorless to light yellow liquid（Density：1.038 g/cm3）
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| Index of Refraction |
n20/D 1.483-1.489
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| LogP |
4.44
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
22
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| Complexity |
304
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(CCCCCCC(OCC1C=CC(O)=C(OC)C=1)=O)C
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| InChi Key |
RBCYRZPENADQGZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H28O4/c1-14(2)8-6-4-5-7-9-18(20)22-13-15-10-11-16(19)17(12-15)21-3/h10-12,14,19H,4-9,13H2,1-3H3
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| Chemical Name |
(4-hydroxy-3-methoxyphenyl)methyl 8-methylnonanoate
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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) |
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 | 3.2424 mL | 16.2122 mL | 32.4244 mL | |
| 5 mM | 0.6485 mL | 3.2424 mL | 6.4849 mL | |
| 10 mM | 0.3242 mL | 1.6212 mL | 3.2424 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.
Link: https://clinicaltrials.gov/ct2/show/NCT01142687
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT01773356
Conditions:ObesityProducts are for research use only; We do not sell to patients
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