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  3. Withanone

Withanone is an active constituent from Withania somnifera roots with multifunctional neuroprotective effect in alleviating cognitive dysfunction. Withanone affords protection against N-methyl-D-aspartate (NMDA)-induced excitotoxicity in Neuron-like cells.

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Withanone Chemical Structure

Withanone Chemical Structure

CAS No. : 27570-38-3

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Description

Withanone is an active constituent from Withania somnifera roots with multifunctional neuroprotective effect in alleviating cognitive dysfunction. Withanone affords protection against N-methyl-D-aspartate (NMDA)-induced excitotoxicity in Neuron-like cells[1][2].

IC50 & Target

NMDA Receptor

 

In Vitro

Withanone (5-20 μM; Neuro2a cells) treatment significantly reverses the cell death induced by NMDA in N2a cells[1].
Withanone (5-20 μM; Neuro2a cells) treatment significantly normalizes Bax and Bcl-2 levels[1].
Attenuation of NMDA-induced intracellular calcium releases by Withanone in N2a cells[1].
Withanone attenuates NMDA-induced Reactive Oxygen Species generation in N2a cells and induces attenuation of mitochondrial membrane motential loss[1].
Withanone treatment down-regulates the expression of cytochrome c[1].
Withanone treatment decteases the Malondialdehyde levels in NMDA-induced excitotoxicity[1].
Withanone shows promise in Alzheimer's disease (AD) treatment because of cognitive benefits and more importantly, mechanisms of action with respect to the fundamental pathophysiology of the disease, not limited to the inhibition of AChE, but also include the modification of Aβ processing, protection against oxidative stress and anti-inflammatory effects. Withanone (24 hours) treatment shows significant protective effect against amyloid β (Aβ) toxicity in Aβ induced toxicity in PC-12 cells[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: Neuro2a (N2a) cells
Concentration: 5 μM, 10 μM, 20 μM
Incubation Time:
Result: Attenuated NMDA-Induced cell death in N2a cells.

Western Blot Analysis[1]

Cell Line: Neuro2a (N2a) cells
Concentration: 5 μM, 10 μM, 20 μM
Incubation Time:
Result: Normalized NMDA-induced alterations in Bax and Bcl-2.
In Vivo

Withanone (5-20 mg/kg; oral administration; daily; for 21 days; male Wistar rats) treatment shows significant improvement in the cognitive skill by inhibiting amyloid β-42 and attenuates the elevated levels of pro-inflammatory cytokines like TNF α, IL-1β, IL-6, MCP-1, Nitric oxide, lipid peroxidation and both β- and γ- secretase enzymatic activity. Administration of Withanone also significantly reverses the decline in acetyl choline and Glutathione (GSH) activity[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male Wistar rats (20-24 weeks; 320-360 g) received ICV injection of STZ[1]
Dosage: 5 mg/kg, 10 mg/kg and 20 mg/kg
Administration: Oral administration; daily; for 21 days
Result: Showed 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 significantly reversed the decline in acetyl choline and Glutathione (GSH) activity.
Molecular Weight

470.60

Formula

C28H38O6

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

C[C@@]12[C@]3([H])[C@]([C@H](O4)[C@H]4[C@]1(CC=CC2=O)O)([H])[C@@]5([H])[C@@](C)([C@]([C@@H]([C@@](O6)([H])CC(C)=C(C)C6=O)C)(O)CC5)CC3

Structure Classification
Initial Source
Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Purity & Documentation
References
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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Withanone
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HY-129692
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