Withanone 

Withanone is an active ingredient from the roots of Withania somnifera and a GRP75 inhibitor. Withanone has multifunctional neuroprotective effects in alleviating cognitive dysfunction. In neuron-like cells, Withanone can inhibit NMDA-induced excitotoxicity. Withanone can inhibit white adipose tissue browning by blocking the formation of the GRP75-ANT2-UCP1 complex, thereby alleviating cancer-related cachexia. Withanone can be used in the research of tumors and nervous system diseases^[1][2][3].

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.

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.

470.60

C₂₈H₃₈O₆

27570-38-3

Solid

White to off-white

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

Room temperature in continental US; may vary elsewhere.

• [1]. Dar NJ, et al. 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.  [Content Brief]

  [2]. Pandey A, et al. Multifunctional neuroprotective effect of Withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunction. Cytokine. 2018 Feb;102:211-221.  [Content Brief]

  [3]. Chen X, et al. GRP75 triggers white adipose tissue browning to promote cancer-associated cachexia. Signal Transduct Target Ther. 2024 Sep 26;9(1):253.  [Content Brief]