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Withanoside IV

CAS# 362472-81-9

Withanoside IV

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Chemical structure

Withanoside IV

3D structure

Chemical Properties of Withanoside IV

Cas No. 362472-81-9 SDF Download SDF
PubChem ID 71312551 Appearance White-beige powder
Formula C40H62O15 M.Wt 782.9
Type of Compound Steroids Storage Desiccate at -20°C
Solubility Soluble in ethanol and methanol; slightly soluble in water; insoluble in n-hexane
Chemical Name (2R)-2-[(1S)-1-[(1S,3R,8S,9S,10R,13S,14S,17R)-1-hydroxy-10,13-dimethyl-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxy-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethyl]-5-(hydroxymethyl)-4-methyl-2,3-dihydropyran-6-one
SMILES CC1=C(C(=O)OC(C1)C(C)C2CCC3C2(CCC4C3CC=C5C4(C(CC(C5)OC6C(C(C(C(O6)COC7C(C(C(C(O7)CO)O)O)O)O)O)O)O)C)C)CO
Standard InChIKey VUQQGHSDHGOYRH-IFUSOADVSA-N
Standard InChI InChI=1S/C40H62O15/c1-17-11-26(53-36(50)22(17)14-41)18(2)23-7-8-24-21-6-5-19-12-20(13-29(43)40(19,4)25(21)9-10-39(23,24)3)52-38-35(49)33(47)31(45)28(55-38)16-51-37-34(48)32(46)30(44)27(15-42)54-37/h5,18,20-21,23-35,37-38,41-49H,6-16H2,1-4H3/t18-,20+,21-,23+,24-,25-,26+,27+,28+,29-,30+,31+,32-,33-,34+,35+,37+,38+,39+,40-/m0/s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Source of Withanoside IV

The herbs of Withania somnifera

Biological Activity of Withanoside IV

DescriptionWithanoside IV improves hindlimb function by facilitating axonal growth and increase in peripheral nervous system myelin level after spinal cord injury. Withanoside IV may prevent or decrease the growth of tumors in human. Withanoside IV showed significant neurite outgrowth activity at a concentration of 1 μM on a human neuroblastoma SH-SY5Y cell line. Withanoside IV (10 micromol/kg/day) significantly improved memory deficits in Abeta(25-35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses.

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Preparing Stock Solutions of Withanoside IV

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 1.2773 mL 6.3865 mL 12.773 mL 25.546 mL 31.9326 mL
5 mM 0.2555 mL 1.2773 mL 2.5546 mL 5.1092 mL 6.3865 mL
10 mM 0.1277 mL 0.6387 mL 1.2773 mL 2.5546 mL 3.1933 mL
50 mM 0.0255 mL 0.1277 mL 0.2555 mL 0.5109 mL 0.6387 mL
100 mM 0.0128 mL 0.0639 mL 0.1277 mL 0.2555 mL 0.3193 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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References on Withanoside IV

Investigating 11 Withanosides and Withanolides by UHPLC-PDA and Mass Fragmentation Studies from Ashwagandha (Withania somnifera).[Pubmed:33163776]

ACS Omega. 2020 Oct 21;5(43):27933-27943.

Withania somnifera (WS), also known as ashwagandha or Indian ginseng, is known for its pharmacological significance in neurodegenerative diseases, stress, cancer, immunomodulatory, and antiviral activity. In this study, the WS extract (WSE) from the root was subjected to ultrahigh-performance liquid chromatography with photodiode array detection (UHPLC-PDA) analysis to separate 11 withanoside and withanolide compounds. The quantification validation was carried out as per ICHQ2R1 guidelines in a single methodology. The calibration curves were linear (r (2) > 0.99) for all 11 compounds within the tested concentration ranges. The limits of detection and quantification were in the range of 0.213-0.362 and 0.646-1.098 mug/mL, respectively. The results were precise (relative standard deviation, <5.0%) and accurate (relative error, 0.01-0.76). All compounds showed good recoveries of 84.77-100.11%. For the first time, withanoside VII, 27-hydroxywithanone, dihydrowithaferin A, and viscosalactone B were quantified and validated along with bioactive compounds Withanoside IV, withanoside V, withaferin A, 12-deoxywithastramonolide, withanolide A, withanone, and withanolide B simultaneously in WS. This UHPLC-PDA method has practical adaptability for ashwagandha raw material, extract, and product manufacturers, along with basic and applied science researchers. The method has been developed on UHPLC for routine analysis. The 11 withanosides and withanolides were confirmed using the fragmentation pattern obtained by the combined use of electrospray ionization and collision-induced dissociation in triple-quadrupole tandem mass spectrometry (TQ-MS/MS) in the WSE.

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation.[Pubmed:33147850]

Molecules. 2020 Nov 2;25(21). pii: molecules25215091.

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 microg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, Withanoside IV-V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1beta induced IL-6 and TNF-alpha cytokine secretions, and decreased TNF-alpha induced NF-kappaB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.

Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor.[Pubmed:32643552]

J Biomol Struct Dyn. 2020 Jul 8:1-14.

SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant Withania somnifera (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (M(pro)) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of -87.01 +/- 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against M(pro) of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV. Communicated by Ramaswamy H. Sarma.

Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities.[Pubmed:31276745]

Food Chem Toxicol. 2019 Oct;132:110659.

Subcritical water extraction (SWE) applied to analyses the bioactives from ashwagandha (W. somnifera) at varying temperature (100-200 degrees C) and extraction time (10-30min). The effect of temperature and time has been investigated in terms of extraction yield (EY), total phenolic content (TPC), cytotoxicity, antioxidant, and enzyme inhibitory activities. The withanosides and withanolides responsible for various biological effects were quantified using high performance liquid chromatography (HPLC). The HPLC analysis revealed Withanoside V, Withanoside IV, 12-Deoxywithastramonolide, Withanolide A, and Withaferin A as a principle bioactive compounds in SWE, with high in concentration compared to microwave-assisted extraction (MAE), Soxhlet extraction (SE) and maceration (MC). For SWE the highest EY (65.6%; 200 degrees C for 30min), TPC (82.5mg GAE/g DE), antioxidant activity (DPPH: 80.3%, FRAP: 60.5% and ABTS: 78.9), and potent enzyme inhibitory effects were observed. The SWE and Withaferin A showed significant reduction in cell viability of cervical cancer (HeLa) cells, with IC50 values 10mg/ml and 8.5muM/ml, respectively but no cytotoxic effect for normal cells (MDCK). Thus, SWE can provide effective extraction for ashwagandha withanosides and withanolides compared MAE, SE and MC to conventional methods, which could be used for extraction of pharmacologically active fractions with therapeutic applications.

Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin.[Pubmed:30403672]

PLoS One. 2018 Nov 7;13(11):e0200053.

Withania somnifera (Ashwagandha) is an efficient medicinal plant known in Ayurveda and Chinese medicine since ancient times, whose extracts are consumed orally as food supplement or as a health tonic owing to its several restorative properties for various CNS disorders, inflammation, tumour, stress, rheumatism etc. In this study, we have analyzed the binding interaction of four derivatives of Withania somnifera (Withanolide A, Withanolide B, Withanoside IV and Withanoside V) with HSA because of their important pharmacological properties. To unravel the binding between derivatives of Withania somnifera and HSA, fluorescence spectroscopy was used. Binding studies were further studied by molecular docking and dynamics and results confirmed greater stability upon binding of derivatives with HSA. Circular dichroism data illustrated change in the secondary structure of protein upon interaction with these derivatives, particularly the helical structure was increased and beta-sheets and random coils were decreased. Furthermore, morphological and topological changes were observed using AFM and TEM upon binding of ligands with HSA indicating that HSA-withnoside/withanolide complexes were formed. All the results cumulatively demonstrate strong binding of withanosides and withanolides derivatives with serum albumin, which should further be explored to study the pharmacokinetics and pharmacodynamics of these derivatives.

Metabolite Profiling in Withania somnifera Roots Hydroalcoholic Extract Using LC/MS, GC/MS and NMR Spectroscopy.[Pubmed:27743505]

Chem Biodivers. 2017 Mar;14(3).

Ashwagandha (Withania somnifera) is a very well-known herbal medicine and it was well studied for its active metabolites throughout the World. Although, nearly 40 withanolides were isolated from W. somnifera root extract, still there is remaining unidentified metabolites due to very low abundance and geographical variation. Advanced separation technology with online identification by mass and nuclear magnetic resonance (NMR) are nowadays used to find out the new compounds in the crude herbal extract. This article described the metabolite profiling of ashwagandha root hydroalcoholic extract using ultra-performance liquid chromatography coupled with a positive ion electrospray ionization tandem mass spectrometry through gas chromatography mass spectrometry (GC/MS) and NMR spectroscopy. A total of 43 possible withanolides was identified and proposed their structures based on the mass of molecular and fragment ions. GC/MS and NMR analysis indicated the presence of several known withanolides including withaferin A, withanolide D, Withanoside IV or VI, withanolide sulfoxide, etc. To the best of our knowledge, dihydrowithanolide D at m/z 473 (tR 7.86 min) and ixocarpalactone A at m/z 505 (tR 8.43 min) were first time identified in the ashwagandha root hydroalcoholic extract. The current study that described the identification of withanolides with summarized literature review might be helpful for designing the experiment to identify of the new chemical constituents in Withania species.

Determination of Withanolides in Withania somnifera by Liquid Chromatography: Single-Laboratory Validation, First Action 2015.17.[Pubmed:27697094]

J AOAC Int. 2016 Nov 1;99(6):1444-1458.

An LC method was developed and validated in 2007 for analyzing Withania somnifera raw material (root) and dried extracts for withanolide content, including Withanoside IV, withanoside V, withaferin A, 12-deoxywithastromonolide, withanolide A, and withanolide B. The method involved the extraction of the analytes with methanol, their subsequent filtration, and then analysis on a C18 column with an acetonitrile gradient and UV detection. Single-laboratory validation yielded linearity generally in the range of 20 to 200 mug/mL for each analyte, with a repeatability precision of RSD < 3% in most cases, and recovery in the range of 90 to 105%. These results compare well with the performance criteria recently detailed in AOAC Standard Method Performance Requirement 2015.007. The method was shown to be rugged with respect to different analysts, equipment, and days of analysis, and the sample solution was shown to be stable for 24 h at room temperature after extraction. The method was reviewed by the AOAC Expert Review Panel on Dietary Supplements (Set 2 Ingredients) and approved for First Action Official MethodSM status.

Evaluation of the bioavailability of major withanolides of Withania somnifera using an in vitro absorption model system.[Pubmed:26605156]

J Adv Pharm Technol Res. 2015 Oct-Dec;6(4):159-64.

Withania somnifera (L.) Dunal, shows several pharmacological properties which are attributed mainly to the withanolides present in the root. The efficacy of medicinally active withanolides constituents depends on the absorption and transportation through the intestinal epithelium. We examined these characteristics by employing the Sino-Veda Madin-Darby canine kidney cells culture system, which under in vitro condition shows the absorption characteristics similar to the human intestinal epithelium. Thus, the aim of the present investigation was to assess the bioavailability of individual withanolides. Withanolides were diluted in Hank's buffered saline at a concentration of 2 mug/ml were tested for permeability studies carried out for 1 h duration. Permeability was measured in terms of efflux pump (P eff) in cm/s. P eff values of withanolide A (WN A), withanone (WNN), 1,2-deoxywithastramonolide (1,2 DWM), withanolide B (WN B), Withanoside IV-V (WS IV-V), and withaferin A were 4.05 x 10(-5), 2.06 x 10(-5), 1.97 x 10(-5), 1.80 x 10(-5), 3.19 x 10(-6), 3.03 x 10(-6) and 3.30 x 10(-7) respectively. In conclusion, the nonpolar and low molecular weight compounds (WN A, WNN, 1,2 DWM, and WN B) were highly permeable. As against this, the glycosylated and polar WS IV and WS V showed low permeability. Surprisingly and paradoxically, the highly biologically active withaferin A was completely impermeable, suggesting that further studies possibly using human epithelial colorectal adenocarcinoma (Caco-2) cells may be needed to delineate the absorption characteristics of withanolides, especially withaferin A.

Enhanced biosynthesis of withanolides by elicitation and precursor feeding in cell suspension culture of Withania somnifera (L.) Dunal in shake-flask culture and bioreactor.[Pubmed:25089711]

PLoS One. 2014 Aug 4;9(8):e104005.

The present study investigated the biosynthesis of major and minor withanolides of Withania somnifera in cell suspension culture using shake-flask culture and bioreactor by exploiting elicitation and precursor feeding strategies. Elicitors like cadmium chloride, aluminium chloride and chitosan, precursors such as cholesterol, mevalonic acid and squalene were examined. Maximum total withanolides detected [withanolide A (7606.75 mg), withanolide B (4826.05 mg), withaferin A (3732.81 mg), withanone (6538.65 mg), 12 deoxy withanstramonolide (3176.63 mg), Withanoside IV (2623.21 mg) and withanoside V (2861.18 mg)] were achieved in the combined treatment of chitosan (100 mg/l) and squalene (6 mM) along with 1 mg/l picloram, 0.5 mg/l KN, 200 mg/l L-glutamine and 5% sucrose in culture at 4 h and 48 h exposure times respectively on 28th day of culture in bioreactor. We obtained higher concentrations of total withanolides in shake-flask culture (2.13-fold) as well as bioreactor (1.66-fold) when compared to control treatments. This optimized protocol can be utilized for commercial level production of withanolides from suspension culture using industrial bioreactors in a short culture period.

Withania somnifera attenuates acid production, acid tolerance and extra-cellular polysaccharide formation of Streptococcus mutans biofilms.[Pubmed:24467542]

Am J Chin Med. 2014;42(1):157-71.

Withania somnifera (Ashwagandha) is a plant of the Solanaceae family. It has been widely used as a remedy for a variety of ailments in India and Nepal. The plant has also been used as a controlling agent for dental diseases. The aim of the present study was to evaluate the activity of the methanol extract of W. somnifera against the physiological ability of cariogenic biofilms and to identify the components of the extract. To determine the activity of the extract, assays for sucrose-dependent bacterial adherence, glycolytic acid production, acid tolerance, and extracellular polysaccharide formation were performed using Streptococcus mutans biofilms. The viability change of S. mutans biofilms cells was also determined. A phytochemical analysis of the extract was performed using TLC and LC/MS/MS. The extract showed inhibitory effects on sucrose-dependent bacterial adherence (>/= 100 mug/ml), glycolytic acid production (>/= 300 mug/ml), acid tolerance (>/= 300 mug/ml), and extracellular polysaccharide formation (>/= 300 mug/ml) of S. mutans biofilms. However, the extract did not alter the viability of S. mutans biofilms cells in all concentrations tested. Based on the phytochemical analysis, the activity of the extract may be related to the presence of alkaloids, anthrones, coumarines, anthraquinones, terpenoids, flavonoids, and steroid lactones (withanolide A, withaferin A, withanolide B, Withanoside IV, and 12-deoxy withastramonolide). These data indicate that W. somnifera may be a potential agent for restraining the physiological ability of cariogenic biofilms.

Optimization of elicitation conditions with methyl jasmonate and salicylic acid to improve the productivity of withanolides in the adventitious root culture of Withania somnifera (L.) Dunal.[Pubmed:22843063]

Appl Biochem Biotechnol. 2012 Oct;168(3):681-96.

Adventitious root cultures derived from leaf derived callus of Withania somnifera (L.) Dunal were treated with methyl jasmonate and salicylic acid independently. Biomass accumulation, culture age, elicitation period, and culture duration were optimized for higher withanolides production in the two best-responding varieties collected from Kolli hills (Eastern Ghats) and Cumbum (Western Ghats) of Tamil Nadu, India. Between the two elicitors, salicylic acid (SA) improved the production of major withanolides (withanolide A, withanolide B, withaferin A, and withanone) as well as minor constituents (12-deoxy withastramonolide, withanoside V, and Withanoside IV) in the Kolli hills variety. Treatment of root biomass (11.70 g FW) on 30-day-old adventitious root cultures with 150 muM SA for 4 h elicitor exposure period resulted in the production of 64.65 mg g(-l) dry weight (DW) withanolide A (48-fold), 33.74 mg g(-l) DW withanolide B (29-fold), 17.47 mg g(-l) DW withaferin A (20-fold), 42.88 mg g(-l) DW withanone (37-fold), 5.34 mg g(-l) DW 12-deoxy withastramonolide (nine fold), 7.23 mg g(-l) DW withanoside V (seven fold), and 9.45 mg g(-l) DW Withanoside IV (nine fold) after 10 days of elicitation (40th day of culture) when compared to untreated cultures. This is the first report on the use of elicitation strategy on the significant improvement in withanolides production in the adventitious root cultures of W. somnifera.

Chlorinated Withanolides from Withania somnifera.[Pubmed:22125584]

Phytochem Lett. 2011 Dec;4(4):411-414.

A chlorinated withanolide, 6alpha-chloro-5beta,17alpha-dihydroxywithaferin A (1), and nine known withanolides, 6alpha-chloro-5beta-hydroxywithaferin A (2), (22R)-5beta-formyl-6beta,27-dihydroxy-1-oxo-4-norwith-24-enolide, withaferin A, 2,3-dihydrowithaferin A, 3-methoxy-2,3-dihydrowithaferin A, 2,3-didehydrosomnifericin, withanone, Withanoside IV and withanoside X, were isolated from Withania somnifera (Solanaceae). All structures were elucidated on the basis of spectroscopic methods (IR, HRESIMS, 1D/2D NMR). X-ray crystallography confirmed the absolute configuration of 1.

Current and future therapeutic strategies for functional repair of spinal cord injury.[Pubmed:21640756]

Pharmacol Ther. 2011 Oct;132(1):57-71.

Spinal cord injury (SCI) causes serious, chronic dysfunction which is difficult to treat. Disability, including long-lasting motor and sensory dysfunction, typically results from damage to the descending and ascending spinal tracts and interneurons and, secondarily, to the neuronal degeneration that occurs proximal and distal to the spinal insult. Numerous strategies are being implemented to protect neurons from damage, to enhance axon growth and to foster cell proliferation. Described in this report are recent clinical trials aimed at testing strategies to restore locomotion after SCI. While laboratory animal studies have indicated that it may be possible to minimize neuronal damage resulting from spinal cord injury, little progress has been made in reducing or reversing the events associated with the chronic phase of this condition. The strategy aiming to inhibit single molecule sometimes shows controversial results. In SCI, a lot of players participate in motor and sensory dysfunctions. Therefore, sufficient functional recovery may be achieved by regulating multiple targets. Regrowth of tracts connecting the brain and spinal cord, and axonal sprouting of propriospinal interneurons are fundamentally important for neuronal network working. In addition, remyelination, protection of neuronal death, inhibition of inflammation, and upregulation of beneficial influence of astrocytes are also quite crucial to supporting the axonal refining. Combination of several strategies might be useful as a practical therapy. Several compounds such as a Sema3A inhibitor, estrogen, Withanoside IV and their relating compounds or other neurotrophic factor-mimicking agents may be candidates for useful SCI therapeutic drugs since those have multi-effects on damaged spinal cord. [corrected].

Sominone enhances neurite outgrowth and spatial memory mediated by the neurotrophic factor receptor, RET.[Pubmed:19594760]

Br J Pharmacol. 2009 Aug;157(8):1427-40.

BACKGROUND AND PURPOSE: Orally administered Withanoside IV (a compound isolated from the roots of Withania somnifera) improved memory deficits in mice with a model of Alzheimer's disease induced by the amyloid peptide Abeta(25-35). Sominone, an aglycone of Withanoside IV, was identified as an active metabolite after oral administration of Withanoside IV. We aimed to identify receptors or associated molecules of sominone, and to investigate the effects of sominone on memory in normal mice. EXPERIMENTAL APPROACH: Phosphorylation levels of 71 molecules were compared between control and sominone-stimulated cortical cultured cells to search for target molecules of sominone. Object location memory and neurite density in the brain were evaluated in sominone-injected mice. KEY RESULTS: Phosphorylation of RET (a receptor for the glial cell line-derived neurotrophic factor, GDNF) was increased in neurons by sominone, without affecting the synthesis and secretion of GDNF. Knockdown of RET prevented sominone-induced outgrowths of axons and dendrites. After a single i.p. injection of sominone into normal mice, they could better memorize scenery information than control mice. Sixty minutes after sominone injection, RET phosphorylation was increased, particularly in the hippocampus of mice. After the memory tests, the densities of axons and dendrites were increased in the hippocampus by sominone administration. CONCLUSIONS AND IMPLICATIONS: Sominone could reinforce the morphological plasticity of neurons by activation of the RET pathway and thus enhance memory. Sominone, a compound with low molecular weight, may be a GDNF-independent stimulator of the RET pathway and/or a novel modulator of RET signalling.

Glycowithanolides accumulation in in vitro shoot cultures of Indian ginseng (Withania somnifera Dunal).[Pubmed:19475989]

Nat Prod Commun. 2009 Apr;4(4):479-82.

Phytochemical investigations of multiple shoot cultures of selected accessions AGB002 and AGB025 of Withania somnifera established in vitro utilizing shoot tip apices cultured on Murashige and Skoog's medium supplemented with BAP (1 mg/L) have been carried out. This has lead to isolation of four glycowithanolides viz. Withanoside IV (WSG-3), Withanoside VI (WSG-3A), Physagulin D (WSG-P) and Withastraronolide (WSC-O). The structures of these have been confirmed on the basis of spectroscopic data. Multiple shoot cultures could be an alternative renewable resource for production of these biologically active molecules.

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