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| 5mg |
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| Targets |
Withanolide A targets brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway [1]
Withanolide A targets apoptosis-related proteins (Bcl-2, Bax, cleaved caspase-3) (IC₅₀ = 24.8 μM for CaOV3 cells, 29.5 μM for SKOV3 cells) [2] Withanolide A targets endothelial nitric oxide synthase (eNOS) [3] Withanolide A targets glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) [4] |
|---|---|
| ln Vitro |
- Neurite regeneration: In PC12 cells and primary cortical neurons, Withanolide A (10-50 nM) dose-dependently promoted neurite outgrowth, increasing neurite length by 45-78% and branch number by 32-65% compared to control; it also upregulated the expression of BDNF and its receptor TrkB via activating the PI3K/Akt pathway [1]
- Antitumor activity: In ovarian carcinoma cell lines CaOV3 and SKOV3, Withanolide A (5-50 μM) exhibited dose-dependent antiproliferative effects, with IC₅₀ values of 24.8 μM and 29.5 μM respectively; it induced apoptosis by increasing Annexin V-positive cells (35-60% at 25 μM), upregulating Bax and cleaved caspase-3/9 expression, and downregulating Bcl-2 expression [2] - Vasorelaxant activity: In rat aortic smooth muscle cells, Withanolide A (1-10 μM) enhanced nitric oxide (NO) generation by 2.3-3.8 folds, which was associated with increased phosphorylation of eNOS (Ser1177); the NO production was abolished by eNOS inhibitors [3] - Neuroprotective activity: In primary hippocampal neurons under hypoxia (1% O₂), Withanolide A (5-20 μM) reduced reactive oxygen species (ROS) accumulation by 40-65%, decreased neuronal apoptosis rate from 48% to 15-28%, and increased intracellular glutathione (GSH) levels by upregulating GCLC and GCLM expression [4] - Anti-clonogenic activity: Withanolide A (10-30 μM) suppressed the clonogenic potential of CaOV3 and SKOV3 cells, reducing colony formation efficiency by 52-75% compared to control [2] |
| ln Vivo |
- Peripheral nerve regeneration: In mice with sciatic nerve crush injury, Withanolide A administration (10 mg/kg, intraperitoneal injection) for 4 weeks significantly promoted nerve regeneration, increasing the number of myelinated axons by 68% and myelin sheath thickness by 55% compared to control; it also restored motor function, as evidenced by improved walking track analysis and increased grip strength [1]
- Hypoxic brain injury protection: In mice with hypoxia-induced cerebral damage, Withanolide A (5 mg/kg, intraperitoneal injection) for 7 days reduced hippocampal neuronal apoptosis by 52%, increased brain GSH levels by 70%, and improved cognitive function in the Morris water maze test (shortening escape latency by 40%) [4] - Vasorelaxant effect: In isolated rat aortic rings precontracted with norepinephrine, Withanolide A (1-10 μM) induced dose-dependent relaxation, with a maximum relaxation rate of 72% at 10 μM; the effect was blocked by L-NAME (eNOS inhibitor) [3] |
| Enzyme Assay |
- GCLC/GCLM activity assay: Total protein was extracted from hypoxic hippocampal neurons, incubated with Withanolide A (5-20 μM) in reaction buffer containing glutamate, cysteine, and ATP; GCLC and GCLM activities were evaluated by measuring the rate of GSH synthesis using a colorimetric assay [4]
- eNOS activity assay: Rat aortic tissue homogenates were prepared and incubated with Withanolide A (1-10 μM) in the presence of L-arginine and NADPH; eNOS activity was determined by detecting NO production via the Griess reaction, and phosphorylation of eNOS was analyzed by Western blot [3] |
| Cell Assay |
- Neurite outgrowth assay: PC12 cells or primary cortical neurons were seeded on poly-L-lysine-coated 96-well plates, incubated overnight, and treated with Withanolide A (10-50 nM) for 72 hours; neurite length and branch number were observed under a phase-contrast microscope and quantified using image analysis software [1]
- Cell viability assay: CaOV3 and SKOV3 cells were seeded in 96-well plates (5×10³ cells/well), treated with Withanolide A (5-50 μM) for 48 hours, and cell viability was measured using the MTT assay; dose-response curves were generated to calculate IC₅₀ values [2] - Apoptosis assay: Ovarian cancer cells were treated with Withanolide A (25 μM) for 48 hours, harvested, stained with Annexin V-FITC and propidium iodide, and apoptotic cells were quantified by flow cytometry; Western blot was performed to detect Bcl-2, Bax, and cleaved caspase-3/9 expression [2] - ROS and GSH detection assay: Primary hippocampal neurons were exposed to hypoxia (1% O₂) and treated with Withanolide A (5-20 μM) for 24 hours; intracellular ROS levels were detected using DCFH-DA fluorescent probe, and GSH content was measured by a colorimetric assay kit [4] - NO detection assay: Rat aortic smooth muscle cells were seeded in 24-well plates, treated with Withanolide A (1-10 μM) for 24 hours, and NO production was measured using the DAF-FM DA fluorescent probe; eNOS phosphorylation was analyzed by Western blot [3] |
| Animal Protocol |
- Sciatic nerve crush injury model: C57BL/6 mice (8-10 weeks old) were subjected to sciatic nerve crush injury using forceps; 24 hours after injury, mice were randomly divided into treatment and control groups (n=8 per group); the treatment group received Withanolide A (10 mg/kg) via intraperitoneal injection, 5 times a week for 4 weeks, while the control group received the same volume of vehicle (DMSO:saline = 1:99); motor function (grip strength, walking track) and nerve histology (myelinated axons, myelin thickness) were evaluated at the end of treatment [1]
- Hypoxic brain injury model: ICR mice (6-8 weeks old) were placed in a hypoxic chamber (8% O₂) for 24 hours to induce cerebral damage; during and after hypoxia, mice were treated with Withanolide A (5 mg/kg) via intraperitoneal injection once daily for 7 days; the vehicle group received 5% DMSO + 10% polyethylene glycol + 85% saline; hippocampal tissues were collected to detect GSH levels, ROS accumulation, and neuronal apoptosis [4] - Rat aortic ring assay: Male SD rats (200-250 g) were euthanized, and the thoracic aorta was isolated and cut into 3 mm-long rings; the rings were mounted in an organ bath containing Krebs-Henseleit buffer (37°C, 95% O₂ + 5% CO₂) and precontracted with norepinephrine (1 μM); Withanolide A (1-10 μM, dissolved in DMSO with final concentration ≤0.1%) was added cumulatively, and vascular tension was recorded using a force transducer [3] |
| Toxicity/Toxicokinetics |
In vitro selective toxicity: Withanolide A showed very low cytotoxicity to normal human mammary epithelial cells (MCF-10A), IC₅₀ > 100 μM, while exhibiting potent antiproliferative activity against ovarian cancer cells [2] - In vivo acute toxicity: In mice, no significant weight loss was observed after administration of Withanolide A at therapeutic doses (5-10 mg/kg, intraperitoneal injection), and serum ALT, AST, BUN, and creatinine (indicators of liver and kidney function) levels were within the normal range [1][4] - Histopathological examination: No significant damage to major organs (liver, kidney, heart, lung, spleen) was observed in mice treated with Withanolide A (10 mg/kg) for 4 weeks [1]
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| References |
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| Additional Infomation |
Withanolide A is a Withanolide. It has been reported that Withanolide A exists in plants of the genus Discopodium penninervium, Withania coagulans, and Withania somnifera, and there is relevant data. Withanolide A is a natural steroidal lactone isolated from the roots and leaves of Withania somnifera (Solanaceae family), commonly known as South African Withanolide [1][3][4]. Its neurogenesis is mediated by the PI3K/Akt/BDNF-TrkB signaling pathway, which plays a key role in neuronal survival and regeneration [1]. Its antitumor mechanism involves activation of the mitochondrial-dependent apoptosis pathway (Bcl-2/Bax/caspase cascade) and inhibition of cancer cell colony formation [2]. Its vasodilatory activity depends on eNOS activation and NO production, suggesting potential application value in the treatment of hypertension and cardiovascular diseases. [3] - It exerts neuroprotective effects by enhancing GSH biosynthesis and reducing oxidative stress, thus combating hypoxic injury. [4] - Solanacetic acid lactone A has potential therapeutic value for neurodegenerative diseases (e.g., Alzheimer's disease, peripheral neuropathy), ovarian cancer, and hypoxic brain injury. [1][2][3][4]
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| Molecular Formula |
C28H38O6
|
|---|---|
| Molecular Weight |
470.59772
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| Exact Mass |
470.267
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| CAS # |
32911-62-9
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| PubChem CID |
11294368
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| Appearance |
White to off-white solid
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| Density |
1.264
|
| Boiling Point |
651.6±55.0 °C(Predicted)
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| Melting Point |
305℃ (DEC.)
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| LogP |
3.495
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
34
|
| Complexity |
1030
|
| Defined Atom Stereocenter Count |
11
|
| SMILES |
CC1=C(C)C(=O)O[C@H](C1)[C@@](C)([C@H]2CC[C@H]3[C@H]4[C@H](CC[C@@]32C)[C@@]5(C)C(=O)C=CC[C@@]5([C@@H]6[C@H]4O6)O)O
|
| InChi Key |
DXWHOKCXBGLTMQ-SFQAJKIESA-N
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| InChi Code |
InChI=1S/C28H38O6/c1-14-13-20(33-24(30)15(14)2)27(5,31)18-9-8-16-21-17(10-12-25(16,18)3)26(4)19(29)7-6-11-28(26,32)23-22(21)34-23/h6-7,16-18,20-23,31-32H,8-13H2,1-5H3/t16-,17-,18-,20+,21-,22-,23-,25-,26-,27+,28-/m0/s1
|
| Chemical Name |
(1S,2S,4S,5R,10R,11S,14S,15S,18S)-15-[(1R)-1-[(2R)-4,5-dimethyl-6-oxo-2,3-dihydropyran-2-yl]-1-hydroxyethyl]-5-hydroxy-10,14-dimethyl-3-oxapentacyclo[9.7.0.02,4.05,10.014,18]octadec-7-en-9-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~10 mg/mL (~21.25 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (2.12 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1249 mL | 10.6247 mL | 21.2495 mL | |
| 5 mM | 0.4250 mL | 2.1249 mL | 4.2499 mL | |
| 10 mM | 0.2125 mL | 1.0625 mL | 2.1249 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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