Withanolide A

Withanolide A
Product Name Withanolide A
CAS No.: 32911-62-9
Catalog No.: CFN91964
Molecular Formula: C28H38O6
Molecular Weight: 470.60 g/mol
Purity: >=98%
Type of Compound: Steroids
Physical Desc.: Powder
Targets: EGFR | NF-kB | TNF-α | Caspase | ROS | NMDAR | PI3K | Akt | MAPK
Source: The herbs of Physali alkekengi
Solvent: Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
Price:
Withanolide A extends the lifespan in human EGFR-driven cancerous Caenorhabditis elegans. Withanolide A may serve as potential neuroprotective agent due to inhibition of MAPK family proteins and activation of PI3K/Akt signaling, it plays an important role in central muscarinic receptor functional balance and activation of antioxidant system in the cerebral cortex of temporal lobe epileptic condition. Withanolide A shows anticancer activity against the SK-Br-3 cells.
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Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).

Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.

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The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.
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    Drug Des Devel Ther. 2017 Jun 22;11:1859-1870.
    Molecular docking, QSAR and ADMET studies of withanolide analogs against breast cancer.[Pubmed: 28694686 ]
    Withanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian traditional practice of medicine. Withanolides are steroidal lactones (highly oxygenated C-28 phytochemicals) and have been reported to exhibit immunomodulatory, anticancer and other activities.
    METHODS AND RESULTS:
    In the present study, a quantitative structure activity relationship (QSAR) model was developed by a forward stepwise multiple linear regression method to predict the activity of Withanolide Analogs against human breast cancer. The most effective QSAR model for anticancer activity against the SK-Br-3 cell showed the best correlation with activity (r2=0.93 and rCV2 =0.90). Similarly, cross-validation regression coefficient (rCV2=0.85) of the best QSAR model against the MCF7/BUS cells showed a high correlation (r2=0.91). In particular, compounds CID_73621, CID_435144, CID_301751 and CID_3372729 have a marked antiproliferative activity against the MCF7/BUS cells, while 2,3-dihydrowithaferin A-3-beta-O-sulfate, withanolide 5, Withanolide A, withaferin A, CID_10413139, CID_11294368, CID_53477765, CID_135887, CID_301751 and CID_3372729 have a high activity against the Sk-Br-3 cells compared to standard drugs 5-fluorouracil (5-FU) and camptothecin.
    CONCLUSIONS:
    Molecular docking was performed to study the binding conformations and different bonding behaviors, in order to reveal the plausible mechanism of action behind higher accumulation of active Withanolide Analogs with β-tubulin. The results of the present study may help in the designing of lead compound with improved activity.
    Mol Neurobiol. 2018 Apr;55(4):2725-2739.
    Attenuation of Glutamate-Induced Excitotoxicity by Withanolide-A in Neuron-Like Cells: Role for PI3K/Akt/MAPK Signaling Pathway.[Pubmed: 28447311 ]
    Glutamate-induced excitotoxicity is one of the major underlying mechanisms for neurodegenerative diseases. Efforts are being made to treat such conditions with an array of natural compounds that can modulate the release of glutamate or the underlying mechanisms associated with it. Withania somnifera extract has potent pharmacologic activity similar to that of Korean Ginseng tea and is used to treat several neuronal disorders. However, to date, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders.
    METHODS AND RESULTS:
    Present study was carried out to investigate Withanolide A, one of the active constituents of Withania somnifera against glutamate-induced excitotoxicity in retinoic acid differentiated Neuro2a neuroblastoma cells. The results indicated that glutamate treatment for 2 h induced death in cells that was significantly attenuated by pre-treatment with MK-801 (specific NMDA receptor antagonist) and different concentrations of Withanolide A. Withanolide A abated the glutamate-induced influx of intracellular calcium and excessive ROS production significantly. Further on, glutamate treatment resulted in increased levels of pro-apoptotic and decreased levels of anti-apoptotic proteins, and these protein levels were normalized by various doses of Withanolide A.
    CONCLUSIONS:
    All of these protective effects were partly due to inhibition of MAPK family proteins and activation of PI3K/Akt signaling. Thus, our results suggest that Withanolide A may serve as potential neuroprotective agent.
    Biochem Cell Biol. 2017 Dec 7.
    Altered muscarinic receptor expression in the cerebral cortex of epileptic rats: Restorative role of Withania somnifera.[Pubmed: 29216436]
    Temporal Lobe Epilepsy involves a sequence of events which can lead to neurotransmitter signalling alterations. Many herbal extracts are considered as alternative therapeutic method for epilepsy management. In the present study, we investigated the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in the management of Temporal Lobe Epilepsy.
    METHODS AND RESULTS:
    Confocal imaging of TOPRO-3 stained cortical sections showed severe damage in epileptic brain. We also observed a reduced antioxidant potential and increased peroxide level in epileptic group. Oxidative stress resulted in the down regulation of CREB, NF-κB and TNF-α with an up regulation of the apoptotic factors Caspase 8, 3 and bax in epileptic group. Epileptic condition also resulted in an increased muscarinic receptor binding and mRNA expression in the cerebral cortex. Withania somnifera and Withanolide A significantly reversed the altered muscarinic receptor expression and reversed the oxidative stress and resultant derailment in cell signalling.
    CONCLUSIONS:
    Thus our studies suggest that Withania somnifera and Withanolide A play an important role in central muscarinic receptor functional balance and activation of antioxidant system in the cerebral cortex of temporal lobe epileptic condition. These findings can be of immense therapeutic significance for epileptic management.
    Exp Gerontol. 2018 Apr;104:113-117.
    Withanolide A extends the lifespan in human EGFR-driven cancerous Caenorhabditis elegans.[Pubmed: 29427754 ]
    The conserved EGFR pathway is linked with multiple cancers in humans including breast, ovarian, and lung carcinoma. Withanolide A, one of the major withanolidal active compounds isolated from the Withania somnifera, extends lifespan and ameliorates stress resistance in wild-type C. elegans by targeting the Insulin/IGF-1 signaling pathway. Up-regulation of IGF1 can transactivate EGFR which inturn reduces longevity and promotes tumor development in an organism.
    METHODS AND RESULTS:
    We examined the effects of Withanolide A on the lifespan of a human EGFR-driven C. elegans transgenic model exhibiting the multivulva (Muv) phenotype. The results showed that WA extends the lifespan of both wild human EGFR-driven C. elegans model (human wild-type tyrosine kinase) as well as models bearing single (L858R), and double mutations (T790M-L858R). The lifespan extension observed in these transgenic strains was 20.35, 24.21 and 21.27%, respectively. Moreover, the reduced fat levels were noticed in both wild-type N2 worms and transgenic strains. These observations support the heathspan promoting effect of WA as lipid-rich diet has been reported to promote tumor development.
    CONCLUSIONS:
    In view of the fact that most of the well known FDA approved drugs such as gefitinib fail to inhibit the EGFR-associated cancers because of these mutations, the present findings show the potential of Withanolide A as a foreseen future nutraceutical to improve the average survival of cancer patients.
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