Physicochemical Properties
| Molecular Formula | C28H38O6 |
| Molecular Weight | 470.60 |
| Exact Mass | 470.267 |
| CAS # | 27570-38-3 |
| PubChem CID | 21679027 |
| Appearance | White to off-white solid powder |
| Density | 1.264g/cm3 |
| Boiling Point | 653.7ºC at 760mmHg |
| Flash Point | 216.5ºC |
| Vapour Pressure | 0mmHg at 25°C |
| Index of Refraction | 1.587 |
| LogP | 3.495 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 34 |
| Complexity | 1030 |
| Defined Atom Stereocenter Count | 11 |
| SMILES | CC1=C(C(=O)O[C@H](C1)[C@@H](C)[C@]2(CC[C@@H]3[C@@]2(CC[C@H]4[C@H]3[C@H]5[C@H](O5)[C@@]6([C@@]4(C(=O)C=CC6)C)O)C)O)C |
| InChi Key | FAZIYUIDUNHZRG-PCTWTJKKSA-N |
| InChi Code | InChI=1S/C28H38O6/c1-14-13-19(33-24(30)15(14)2)16(3)27(31)12-9-17-21-18(8-11-25(17,27)4)26(5)20(29)7-6-10-28(26,32)23-22(21)34-23/h6-7,16-19,21-23,31-32H,8-13H2,1-5H3/t16-,17+,18+,19-,21+,22+,23+,25+,26+,27+,28+/m1/s1 |
| Chemical Name | (1S,2S,4S,5R,10R,11S,14S,15S,18S)-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]ethyl]-5,15-dihydroxy-10,14-dimethyl-3-oxapentacyclo[9.7.0.02,4.05,10.014,18]octadec-7-en-9-one |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | NMDA Receptor |
| ln Vitro | Treatment with withanone (5–20 μM; Neuro2a cells) dramatically reverses the NMDA-induced cell death in N2a cells[1]. Treatment of Neuro2a cells with withanone (5–20 μM) significantly returns Bax and Bcl-2 levels to normal[1]. In N2a cells, Withanone attenuates NMDA-induced intracellular calcium releases[1]. In N2a cells, withanone reduces the production of reactive oxygen species (ROS) generated by NMDA and reduces the loss of mitochondrial membrane motential [1]. Cytochrome C expression is down-regulated by withanone therapy [1]. When NMDA-induced excitotoxicity is treated with withanone, the levels of malondialdehyde are reduced[1]. Because of its cognitive benefits and, more importantly, its mechanisms of action regarding the underlying pathophysiology of the disease—which go beyond the inhibition of AChE and include modifications to Aβ processing, protection against oxidative stress, and anti-inflammatory effects—withanone shows promise in the treatment of Alzheimer's disease (AD). When administered for 24 hours, withanone significantly reduces the toxicity caused by amyloid β (Aβ) in PC-12 cells [2]. |
| ln Vivo | Male Wistar rats were given withanone (5–20 mg/kg) orally once a day for 21 days. This treatment significantly improved the rats' cognitive abilities by blocking amyloid β–42 and reducing the levels of pro-inflammatory cytokines such as TNF α, IL-1β, IL-6, MCP-1, nitric oxide, lipid peroxidation, and both β- and γ-secretase enzyme activity. Glutathione (GSH) and acetyl choline declines are also significantly stopped by withanone administration[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: Neuro2a (N2a) cells Tested Concentrations: 5 μM, 10 μM, 20 μM Incubation Duration: Experimental Results: Attenuated NMDA-Induced cell death in N2a cells. Western Blot Analysis[1] Cell Types: Neuro2a (N2a) cells Tested Concentrations: 5 μM, 10 μM, 20 μM Incubation Duration: Experimental Results: Normalized NMDA-induced alterations in Bax and Bcl-2. |
| Animal Protocol |
Animal/Disease Models: Male Wistar rats (20-24 weeks; 320-360 g) received ICV injection of STZ[1] Doses: 5 mg/kg, 10 mg/kg and 20 mg/kg Route of Administration: Oral administration; daily; for 21 days Experimental Results: demonstrated significant improvement in the cognitive skill by inhibiting amyloid β-42 and attenuated the elevated levels of pro-inflammatory cytokines like TNF alpha, IL-1β, IL-6, MCP-1, Nitric oxide, lipid peroxidation and both β- and γ-secretase enzymatic activity. Also Dramatically reversed the decline in acetyl choline and Glutathione (GSH) activity. |
| References |
[1]. Withanone, an Active Constituent from Withania somnifera, Affords Protection Against NMDA-Induced Excitotoxicity in Neuron-Like Cells. Mol Neurobiol. 2017 Sep;54(7):5061-5073. [2]. Multifunctional neuroprotective effect of Withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunction. Cytokine. 2018 Feb;102:211-221. |
| Additional Infomation | Withanone has been reported in Discopodium penninervium, Physalis philadelphica, and Withania somnifera with data available. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1249 mL | 10.6247 mL | 21.2495 mL | |
| 5 mM | 0.4250 mL | 2.1249 mL | 4.2499 mL | |
| 10 mM | 0.2125 mL | 1.0625 mL | 2.1249 mL |