| Size | Price | Stock | Qty |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| ln Vivo |
In rats, gymnema glycoside oral bioavailability is low (around 14%) [2]. Rats have a high clearance rate and a brief half-life for Gymnema lutein [2]. Gymnema glycosides have a high intrinsic clearance rate, a short intrinsic half-life (about 7 minutes), and a short apparent half-life [2]. They are very quickly digested.
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| Enzyme Assay |
Rat liver microsome stability assay: Gymnemagenin (1 µM) was incubated with rat liver microsomes (0.5 mg protein/mL) in a reaction mixture containing NADP (1.3 mM), glucose-6-phosphate (3.3 mM), glucose-6-phosphate dehydrogenase (0.4 U/mL), and MgCl2 (3.3 mM) in phosphate buffer pH 7.4. The reaction was carried out at 37°C for time points 0, 5, 10, 20, 30, and 60 min. The reaction was terminated by adding ice-cold acetonitrile, followed by centrifugation. The supernatant was diluted with water and analyzed by LC-MS/MS. The intrinsic half-life (T1/2,int) was calculated from the slope of the semi-log plot of analyte area vs. time, and in vitro intrinsic clearance (CLint,app) was determined. Quality control compounds (verapamil, desipramine, metoprolol) were used to verify enzyme activity [2].
The in vitro intrinsic clearance was scaled to in vivo intrinsic clearance using microsomal protein content (45 mg/g liver) and liver weight (20 g liver/kg body weight for rat) [2]. |
| Cell Assay |
Caco-2 permeability assay (apical to basal and basal to apical): Caco-2 cells were seeded at 6.3 × 10^4 cells/cm^2 on apical plates and cultured for 21 days in DMEM with 10% FBS, 1% glutamine, penicillin (100 U/mL), streptomycin (100 µg/mL), and 1% nonessential amino acids at 37°C, 5% CO2, and controlled humidity. For apical-to-basal transport, apical wells were washed with buffer pH 6.5 and basal wells with buffer pH 7.4. Then 250 µL of buffer pH 7.4 was added to the basal plate, and 75 µL of gymnemagenin (2 µM in buffer pH 6.5) was added to the apical wells (n=6). For basal-to-apical transport, apical wells were washed with buffer pH 7.4 and basal wells with buffer pH 6.5. Then 250 µL of buffer pH 6.5 was added to the basal plate, and 75 µL of gymnemagenin (2 µM in buffer pH 7.4) was added to the apical wells (n=6). The assembly was incubated at 37°C for 2.5 h under 95% air and 5% CO2. After incubation, aliquots from acceptor wells were diluted and quantified by LC-MS/MS. Apparent permeability (Papp) was calculated using the formula Papp = [Va / (area × time)] × (acceptor concentration / donor concentration). The efflux ratio (EFR) was calculated as Papp,B-A / Papp,A-B. Membrane integrity was assessed by transepithelial electrical resistance (TEER) measurement during culture and by lucifer yellow permeability after the experiment (fluorescence at Ex 432 nm/Em 530 nm); wells with >1% fluorescence relative to initial donor solution were excluded [2].
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| Animal Protocol |
Pharmacokinetic study in rats: Male Wistar rats (180–200 g) were used. Gymnemagenin was formulated as a solution in 10% DMSO, 30% propylene glycol, and 5% glucose solution (q.s. to volume). For oral administration, a dose of 5 mg/kg was given with a dose volume of 5 mL/kg. For intravenous administration, a dose of 1 mg/kg was given with a dose volume of 2 mL/kg. Animals were divided into two groups (n=6 each): oral group and IV group. Blood samples (approx. 130 µL) were collected at predetermined time points. Plasma was separated and analyzed for gymnemagenin concentration by LC-MS/MS [2].
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| ADME/Pharmacokinetics |
In vitro rat liver microsome stability: Gymnemagenin showed an intrinsic half-life (T1/2,int) of 7.31 ± 0.51 min, an in vitro intrinsic clearance (CLint,app) of 190.08 ± 13.01 µL/min/mg microsomal protein, and a scaled in vivo intrinsic clearance of 24.12 ± 1.65 L/h/kg [2].
Caco-2 permeability: Gymnemagenin exhibited poor apical-to-basal permeability (Papp,A-B) of 1.31 ± 0.19 × 10^{-6} cm/s, high basal-to-apical permeability (Papp,B-A) of 31.89 ± 0.76 × 10^{-6} cm/s, and a very high efflux ratio (EFR) of 24.49 ± 3.05, indicating it is a substrate of efflux transporters (likely P-gp) [2]. Rat pharmacokinetics after oral administration (5 mg/kg): Cmax = 45.91 ± 5.89 ng/mL, Tmax = 0.44 ± 0.13 h, terminal half-life (T1/2) = 1.33 ± 0.12 h, clearance (CL) = 53.49 ± 9.23 L/h/kg, AUC(0-t) = 89.65 ± 14.90 ng·h/mL, AUC(0-∞) = 95.53 ± 16.02 ng·h/mL. Oral bioavailability (F) = 14.18 ± 2.38% [2]. Rat pharmacokinetics after intravenous administration (1 mg/kg): terminal half-life (T1/2) = 0.41 ± 0.03 h, clearance (CL) = 7.49 ± 0.81 L/h/kg, volume of distribution (Vd) = 1.53 ± 0.31 L/kg, AUC(0-t) = 134.09 ± 15.78 ng·h/mL, AUC(0-∞) = 134.74 ± 15.77 ng·h/mL. Plasma exposure beyond 4 h (IV) and 8 h (oral) was below quantitation limits [2]. |
| References | |
| Additional Infomation |
Reports indicate that Gymnema sylvestre contains gymnospermine, and relevant data is available for reference. See also: Gymnema sylvestre leaves (partial).
Gymnemagenin is a triterpenoid aglycone of gymnemic acids and is considered a wonder drug for diabetes and obesity, also possessing antiviral properties [1]. It is naturally found in the leaves and roots of Gymnema sylvestre [1]. An endophytic fungus Penicillium oxalicum isolated from the leaves of G. sylvestre was found to produce gymnemagenin in culture medium, as confirmed by TLC, HPLC, FTIR, UV, and 1H NMR analyses, offering an alternative production method that is more economical and environmentally friendly [1]. Despite its therapeutic potential, gymnemagenin exhibits poor drug-like properties due to rapid hepatic metabolism, low intestinal permeability, and high efflux, resulting in low oral bioavailability [2]. |
| Molecular Formula |
C30H50O6
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|---|---|
| Molecular Weight |
506.7144
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| Exact Mass |
506.36
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| CAS # |
22467-07-8
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| PubChem CID |
10051937
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| Appearance |
White to off-white solid
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
634.5±55.0 °C at 760 mmHg
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| Melting Point |
330-331℃
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| Flash Point |
262.0±26.1 °C
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| Vapour Pressure |
0.0±4.2 mmHg at 25°C
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| Index of Refraction |
1.598
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| LogP |
3.98
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
36
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| Complexity |
932
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| Defined Atom Stereocenter Count |
12
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| SMILES |
O([H])[C@@]1([H])C([H])([H])[C@]2(C([H])([H])[H])C(=C([H])C([H])([H])[C@]3([H])[C@@]4(C([H])([H])[H])C([H])([H])C([H])([H])[C@@]([H])([C@@](C([H])([H])[H])(C([H])([H])O[H])[C@]4([H])C([H])([H])C([H])([H])[C@]32C([H])([H])[H])O[H])[C@]2([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])[C@]([H])([C@@]([H])([C@@]21C([H])([H])O[H])O[H])O[H]
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| InChi Key |
VKJLHZZPVLQJKG-ABHKXHSUSA-N
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| InChi Code |
InChI=1S/C30H50O6/c1-25(2)13-18-17-7-8-20-26(3)11-10-21(33)27(4,15-31)19(26)9-12-28(20,5)29(17,6)14-22(34)30(18,16-32)24(36)23(25)35/h7,18-24,31-36H,8-16H2,1-6H3/t18-,19+,20+,21-,22-,23-,24-,26-,27-,28+,29+,30-/m0/s1
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| Chemical Name |
(3R,4R,4aR,5S,6aR,6aS,6bR,8aR,9R,10S,12aR,14bS)-4a,9-bis(hydroxymethyl)-2,2,6a,6b,9,12a-hexamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-3,4,5,10-tetrol
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9735 mL | 9.8676 mL | 19.7352 mL | |
| 5 mM | 0.3947 mL | 1.9735 mL | 3.9470 mL | |
| 10 mM | 0.1974 mL | 0.9868 mL | 1.9735 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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