Withanone
(Synonyms: NSC 179884) 目录号 : GC48969
A phytochemical with diverse biological activities
Cas No.:27570-38-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >90.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Withanone is a phytochemical that has been found in W. somnifera and has diverse biological activities.1,2,3 It inhibits the protein-protein interaction between human angiotensin-converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein receptor-binding domain (IC50 = 0.33 ng/ml).1 Withanone (10 µg/ml) protects against DNA damage, oxidative stress, and premature senescence induced by the industrial contaminant methoxyacetic acid in TIG-1 human fibroblasts.2 In vivo, withanone (5-20 mg/kg) decreases brain levels of amyloid-β 1-42 (Aβ42), malondialdehyde (MDA), TNF-α, IL-1β, and IL-6, increases brain levels of acetylcholine, and improves cognitive function in a rat model of streptozotocin-induced sporadic Alzheimer’s disease.3
1.Balkrishna, A., Pokhrel, S., Singh, H., et al.Withanone from Withania somnifera attenuates SARS-CoV-2 RBD and host ACE2 interactions to rescue spike protein induced pathologies in humanized zebrafish modeDrug Des. Devel. Ther.151111-1133(2021) 2.Priyandoko, D., Ishii, T., Kaul, S.C., et al.Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolitePLoS One6(5)e19552(2011) 3.Pandey, A., Bani, S., Dutt, P., et al.Multifunctional neuroprotective effect of withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunctionCytokine102211-221(2018)
| Cas No. | 27570-38-3 | SDF | |
| 别名 | NSC 179884 | ||
| Canonical SMILES | O=C(C(C)=C(C)C1)O[C@@]1([H])[C@@H](C)[C@@]2(O)CC[C@@]3([H])[C@]4([H])[C@H]5[C@H](O5)[C@@]([C@@]6(C)[C@@]4([H])CC[C@@]32C)(O)CC=CC6=O | ||
| 分子式 | C28H38 | 分子量 | 470.6 |
| 溶解度 | Chloroform: soluble,Ethyl Acetate: slightly soluble,Methanol: slightly soluble | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1249 mL | 10.6247 mL | 21.2495 mL |
| 5 mM | 0.425 mL | 2.1249 mL | 4.2499 mL |
| 10 mM | 0.2125 mL | 1.0625 mL | 2.1249 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Withanone from Withania somnifera Attenuates SARS-CoV-2 RBD and Host ACE2 Interactions to Rescue Spike Protein Induced Pathologies in Humanized Zebrafish Model
Drug Des Devel Ther 2021 Mar 11;15:1111-1133.PMID:33737804DOI:10.2147/DDDT.S292805.
Purpose: SARS-CoV-2 engages human ACE2 through its spike (S) protein receptor binding domain (RBD) to enter the host cell. Recent computational studies have reported that Withanone and withaferin A, phytochemicals found in Withania somnifera, target viral main protease (MPro) and host transmembrane TMPRSS2, and glucose related protein 78 (GRP78), respectively, implicating their potential as viral entry inhibitors. Absence of specific treatment against SARS-CoV-2 infection has encouraged exploration of phytochemicals as potential antivirals. Aim: This study aimed at in silico exploration, along with in vitro and in vivo validation of antiviral efficacy of the phytochemical Withanone. Methods: Through molecular docking, molecular dynamic (MD) simulation and electrostatic energy calculation the plausible biochemical interactions between Withanone and the ACE2-RBD complex were investigated. These in silico observations were biochemically validated by ELISA-based assays. Withanone-enriched extract from W. somnifera was tested for its ability to ameliorate clinically relevant pathological features, modelled in humanized zebrafish through SARS-CoV-2 recombinant spike (S) protein induction. Results: Withanone bound efficiently at the interacting interface of the ACE2-RBD complex and destabilized it energetically. The electrostatic component of binding free energies of the complex was significantly decreased. The two intrachain salt bridge interactions (K31-E35) and the interchain long-range ion-pair (K31-E484), at the ACE2-RBD interface were completely abolished by Withanone, in the 50 ns simulation. In vitro binding assay experimentally validated that Withanone efficiently inhibited (IC50=0.33 ng/mL) the interaction between ACE2 and RBD, in a dose-dependent manner. A withanone-enriched extract, without any co-extracted withaferin A, was prepared from W. somnifera leaves. This enriched extract was found to be efficient in ameliorating human-like pathological responses induced in humanized zebrafish by SARS-CoV-2 recombinant spike (S) protein. Conclusion: In conclusion, this study provided experimental validation for computational insight into the potential of Withanone as a potent inhibitor of SARS-CoV-2 coronavirus entry into the host cells.
The Natural Products Withaferin A and Withanone from the Medicinal Herb Withania somnifera Are Covalent Inhibitors of the SARS-CoV-2 Main Protease
J Nat Prod 2022 Oct 28;85(10):2340-2350.PMID:36098617DOI:10.1021/acs.jnatprod.2c00521.
The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) created a global health crisis. The ability of vaccines to protect immunocompromised individuals and from emerging new strains are major concerns. Hence antiviral drugs against SARS-CoV-2 are essential. The SARS-CoV-2 main protease Mpro is vital for replication and an important target for antivirals. Using CMap analysis and docking studies, withaferin A (wifA) and Withanone (win), two natural products from the medicinal herb Withania somnifera (ashwagandha), were identified as promising candidates that can covalently inhibit the viral protease Mpro. Cell culture, enzymatic, LC-MS/MS, computational, and equilibrium dialysis based assays were performed. DFT calculations indicated that wifA and win can form stable adducts with thiols. The cytotoxicity of Mpro was significantly reduced by wifA and win. Both wifA and win were found to irreversibly inhibit 0.5 μM Mpro with IC50 values of 0.54 and 1.8 μM, respectively. LC-MS/MS analysis revealed covalent adduct formation with wifA at cysteines 145 and 300 of Mpro. The natural products wifA and win can irreversibly inhibit the SARS-CoV-2 main protease Mpro. Based on the work presented here we propose that both wifA and win have the potential to be safely used as preventative and therapeutic interventions for COVID-19.
Withanone Ameliorates Stress Symptoms in Caenorhabditis Elegans by Acting through Serotonin Receptors
Pharmacopsychiatry 2021 Sep;54(5):215-223.PMID:33957677DOI:10.1055/a-1349-3870.
Introduction: Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of Withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods. Methods: WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H2DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (ser-1, ser-4, ser-7) and serotonin transporter (mod-5). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6. Results: WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5. Limitations: Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings. Conclusion: WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression.
Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells
J Biomol Struct Dyn 2022 Jan;40(1):1-13.PMID:32469279DOI:10.1080/07391102.2020.1775704.
Coronavirus disease 2019 (COVID-19) initiated in December 2019 in Wuhan, China and became pandemic causing high fatality and disrupted normal life calling world almost to a halt. Causative agent is a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). While new line of drug/vaccine development has been initiated world-wide, in the current scenario of high infected numbers, severity of the disease and high morbidity, repurposing of the existing drugs is heavily explored. Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. Using the strengths of molecular docking and molecular dynamics simulations, we examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) and caffeic acid phenethyl ester to TPMRSS2 in comparison to its known inhibitor, Camostat mesylate. We found that both Wi-A and Wi-N could bind and stably interact at the catalytic site of TMPRSS2. Wi-N showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. Furthermore, we investigated the effect of Wi-N on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of Wi-N to block SARS-CoV-2 entry into the host cells. Since the natural compounds are easily available/affordable, they may even offer a timely therapeutic/preventive value for the management of SARS-CoV-2 pandemic. We also report that Wi-A/Wi-N content varies in different parts of Ashwagandha and warrants careful attention for their use.Communicated by Ramaswamy H. Sarma.
Effect of Ashwagandha Withanolides on Muscle Cell Differentiation
Biomolecules 2021 Oct 4;11(10):1454.PMID:34680087DOI:10.3390/biom11101454.
Withania somnifera (Ashwagandha) is used in Indian traditional medicine, Ayurveda, and is believed to have a variety of health-promoting effects. The molecular mechanisms and pathways underlying these effects have not yet been sufficiently explored. In this study, we investigated the effect of Ashwagandha extracts and their major withanolides (withaferin A and Withanone) on muscle cell differentiation using C2C12 myoblasts. We found that withaferin A and Withanone and Ashwagandha extracts possessing different ratios of these active ingredients have different effects on the differentiation of C2C12. Withanone and withanone-rich extracts caused stronger differentiation of myoblasts to myotubes, deaggregation of heat- and metal-stress-induced aggregated proteins, and activation of hypoxia and autophagy pathways. Of note, the Parkinson's disease model of Drosophila that possess a neuromuscular disorder showed improvement in their flight and climbing activity, suggesting the potential of Ashwagandha withanolides for the management of muscle repair and activity.