| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Vaccarin activates the AMPK signaling pathway (via upstream kinase LKB1, without changing the AMP/ATP ratio). It increases phosphorylation of AMPK (Thr172), FOXO1 (Ser256), GSK3β (Ser9), and ACC (Ser79); reduces protein expression of PEPCK, G6Pase, SREBP1, and FAS; and increases glycogen synthesis. [1]
Vaccarin activates the MAPK/ERK and PI3K/AKT signaling pathways in vivo, increasing phosphorylation of bFGFR, Akt, and Erk. [2] |
|---|---|
| ln Vitro |
In HepG2 cells treated with glucosamine (GlcN, 18 mM) to induce insulin resistance, Vaccarin (5 μM, 24 h) reversed GlcN-induced glucose production increase, reduced protein levels of PEPCK and G6Pase, enhanced FOXO1 phosphorylation, increased glycogen levels, increased GSK3β phosphorylation (Ser9), and decreased GS phosphorylation (Ser641). Vaccarin restored GlcN-induced inhibition of AMPK phosphorylation. The AMPK inhibitor Compound C (20 μM) abolished Vaccarin's effects on glucose production, PEPCK/G6Pase expression, glycogen synthesis, AMPK/FOXO1/GSK3β phosphorylation, and GS phosphorylation. The AMPK activator AICAR (1 mM) mimicked Vaccarin's effects but no synergy was observed with combination. Vaccarin had no effect on AMPK or GSK3β phosphorylation under normal physiological conditions. [1]
In HepG2 cells exposed to free fatty acids (FFAs, oleate/palmitate 2:1 ratio, 1 mM each) to induce steatosis, Vaccarin (5 μM, 24 h) significantly reduced macro-lipid droplets (Oil Red O staining), decreased TG accumulation, reversed FFAs-induced downregulation of ACC phosphorylation (Ser79), and reduced protein levels of SREBP1 and FAS. Vaccarin restored AMPK phosphorylation. Pre-incubation with Compound C (20 μM) completely blocked Vaccarin's inhibitory effects on TG deposition, FAS and SREBP1 protein expression, and eliminated the enhanced phosphorylation of ACC and AMPK. AICAR (1 mM) also rectified the detrimental effects of FFAs on FAS, SREBP1, ACC, and AMPK. Vaccarin-induced AMPK activation was dependent on LKB1 phosphorylation but not on changes in intracellular AMP/ATP ratio. [1] |
| ln Vivo |
In STZ/HFD-induced type 2 diabetic mice, chronic administration of Vaccarin (1 mg/kg body weight, intraperitoneal injection, daily for 4 weeks) decreased fasting blood glucose levels, increased liver glycogen content (evidenced by PAS-stained liver sections), improved glucose tolerance (GTT) and insulin sensitivity (ITT). Vaccarin treatment normalized the dysregulated phosphorylation of IRS-1 (Ser307) in the livers of T2DM mice. [1]
In STZ/HFD mice, Vaccarin (1 mg/kg, i.p., daily for 4 weeks) lowered serum TC, TG, LDL-C, and NEFA levels (no significant effect on HDL-C), reduced liver weight/body weight ratio, decreased liver TC and TG levels, normalized hepatic dysfunction (ALT, AST), and reduced lipid accumulation (Oil Red O staining) in the liver. Vaccarin upregulated PEPCK, G6Pase, and phosphorylated GS levels in the liver, increased phosphorylated ACC levels, reduced FAS expression, and rescued AMPK/FOXO1/GSK3β signaling. [1] In a rat skin excision wound model (full-thickness 1 cm diameter wounds on both sides of the back), topical application of Vaccarin (0.1% in ointment, 0.02 g per wound, once daily) significantly promoted wound closure percentage compared to vehicle control on days 3, 6, 9, and 11 (P < 0.05 to P < 0.01). Histopathology (H&E staining) showed that Vaccarin-treated wounds exhibited uniform and thick granulation tissue formation, marked proliferation of fibroblasts, collagen deposition, and few inflammatory cells by day 6; by day 9, thicker granulation tissue with fibroblasts and collagen; by day 11, thick compact extracellular matrix covered by epithelial layer resembling normal skin with blood vessels. PCNA immunohistochemistry showed that Vaccarin promoted proliferation of fibroblasts and endothelial cells while reducing inflammatory cell proliferation over time. CD31 immunohistochemistry revealed significantly increased microvascular density (MVD) in the Vaccarin-treated group. Immunohistochemistry and Western blot showed that Vaccarin increased expression of p-bFGFR (but not p-VEGFR), p-Akt, and p-Erk in the wound site. Immunofluorescence double staining of CD31 and bFGFR showed that vascular endothelial cells significantly proliferated in the Vaccarin-treated group. [2] |
| Cell Assay |
HepG2 cells were cultured in DMEM containing 25 mM glucose, 10% FBS, 100 U/ml penicillin, and 100 μg/ml streptomycin at 37°C in 5% CO2. To induce insulin resistance, cells were exposed to glucosamine (GlcN, 18 mM) for 18 h, then treated with Vaccarin (5 μM) for 24 h. For AMPK inhibition or activation, cells were pretreated with Compound C (20 μM) or AICAR (1 mM) for 30 min before Vaccarin plus GlcN for 24 h. Cell viability was measured using CCK-8 assay. Glucose production was measured by replacing medium with DMEM without phenol red containing 2 mM sodium pyruvate and 20 mM sodium lactate, and after 3 h glucose concentration was measured using a GO assay kit. Glycogen levels were quantified using a Glycogen Assay Kit. Protein expression was analyzed by Western blot using antibodies against total and phosphorylated AMPK, FOXO1, GS, GSK3, ACC, PEPCK, SREBP1, FAS, and β-actin. [1]
To induce steatosis, HepG2 cells were exposed to free fatty acids (FFAs, oleate/palmitate 2:1 ratio, 1 mM each) for 24 h, then treated with Vaccarin (5 μM) for 24 h. For inhibition studies, cells were pretreated with Compound C (20 μM) for 30 min. Lipid accumulation was evaluated by Oil Red O staining: cells fixed with 10% formalin, stained with Oil Red O reagent (60% dye, 40% water), washed with 60% ethanol and PBS, then photographed. TG content was quantified using a TG kit. AMP/ATP ratio was measured by HPLC. Protein expression was assessed by Western blot. [1] No in vitro cell assays were performed in the wound healing study. [2] |
| Animal Protocol |
Male C57BL/6J mice (6-week-old) were fed a high-fat diet (HFD, 21.8 kJ/g, 60% energy as fat) after a single intraperitoneal injection of streptozotocin (STZ, 120 mg/kg body weight in 10 mM citrate buffer, pH 4.0) following a 4 h fast. Eight weeks after STZ injection, mice received intraperitoneal injections of Vaccarin (1 mg/kg body weight) or vehicle daily for 4 weeks. Insulin tolerance test (ITT): mice fasted for 6 h, then injected with insulin (0.75 units/kg, i.p.), blood glucose measured at 0, 15, 30, 60, 90 min. Glucose tolerance test (GTT): mice fasted for 12 h, then injected with glucose (2.0 g/kg, i.p.), blood glucose measured similarly. After euthanasia, serum and liver samples were collected for biochemical analysis (TC, TG, HDL, LDL, NEFA, AST, ALT) and histological staining (H&E, Oil Red O, PAS). [1]
Sprague-Dawley male rats (8-week-old, 200-220 g) were anesthetized, back hair clipped, skin washed. Full-thickness skin excision wounds of 1 cm diameter were made on both sides of the back. The left wound received 0.02 g of vehicle ointment, and the right wound received 0.02 g of ointment containing 0.1% Vaccarin. Wound areas were measured daily. On days 3, 6, 9, and 11, four animals per group were euthanized, and traumatic skin was fixed in 4% buffered paraformaldehyde. Wound closure percentage = [(area day 0 - open area day n)/area day 0] × 100. Positive control MEBO (Moist Exposed Burn Ointment) data were presented in supplementary material. Histopathological evaluation: skin sections (5 μm) stained with H&E. Immunohistochemistry: sections incubated with primary antibodies against p-bFGFR (1:50), p-VEGFR (1:50), PCNA (1:100), CD31 (1:25), p-Erk (1:40), p-Akt (1:40) at 4°C overnight, then secondary biotinylated IgG (1:2000), stained with DAB. Immunofluorescence: anti-bFGFR (1:50) and anti-CD31 (1:25), followed by FITC-conjugated anti-rabbit IgG or Cy3-conjugated anti-mouse IgG. Western blot: protein extracts from skin tissue analyzed with antibodies against p-bFGFR, bFGFR, p-Akt, Akt, p-Erk, Erk, and β-tubulin. [2] |
| References |
|
| Additional Infomation |
Vaccarin is a flavonoid compound belonging to the glycoside class. It has been reported that vaccarin exists in Gypsophila vaccaria, and relevant data are available for reference.
Vaccarin attenuates insulin resistance and steatosis by activating the AMPK signaling pathway, reducing gluconeogenesis (via FOXO1 phosphorylation and decreased PEPCK/G6Pase), increasing glycogenesis (via GSK3β-mediated GS activation), and inhibiting lipogenesis (via SREBP1 and FAS downregulation, ACC phosphorylation). These effects were reversed by AMPK inhibitor Compound C, and AMPK activation by Vaccarin was dependent on LKB1 but not on AMP/ATP ratio. In STZ/HFD mice, Vaccarin improved hyperglycemia, hyperlipidemia, hepatic steatosis, and insulin resistance. [1] Vaccarin promotes angiogenesis and accelerates wound healing in vivo by increasing expression of p-Akt, p-Erk, and p-bFGFR, mediated by MAPK/ERK and PI3K/AKT signaling pathways. It increases microvascular density, fibroblast and endothelial cell proliferation, and collagen deposition in the wound site. [2] |
| Molecular Formula |
C32H38O19
|
|---|---|
| Molecular Weight |
726.6327
|
| Exact Mass |
726.2
|
| CAS # |
53452-16-7
|
| PubChem CID |
71307582
|
| Appearance |
Light yellow to yellow solid
|
| Density |
1.8±0.1 g/cm3
|
| Boiling Point |
1088.1±65.0 °C at 760 mmHg
|
| Flash Point |
345.6±27.8 °C
|
| Vapour Pressure |
0.0±0.3 mmHg at 25°C
|
| Index of Refraction |
1.762
|
| LogP |
-0.74
|
| Hydrogen Bond Donor Count |
12
|
| Hydrogen Bond Acceptor Count |
19
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
51
|
| Complexity |
1220
|
| Defined Atom Stereocenter Count |
14
|
| SMILES |
O1[C@]([H])(C([H])([H])O[H])[C@]([H])([C@@]([H])([C@]([H])(C1([H])C1C(=C([H])C2=C(C(C([H])=C(C3C([H])=C([H])C(=C([H])C=3[H])O[C@@]3([H])[C@@]([H])([C@]([H])([C@@]([H])([C@@]([H])(C([H])([H])O[H])O3)O[H])O[H])O[H])O2)=O)C=1O[H])O[H])O[C@@]1([H])[C@@]([H])([C@]([H])([C@]([H])(C([H])([H])O1)O[H])O[H])O[H])O[H])O[H]
|
| InChi Key |
GYIKGLVKALOGDP-HLEFUGOVSA-N
|
| InChi Code |
InChI=1S/C32H38O19/c33-7-17-23(40)26(43)30(51-31-27(44)21(38)14(37)9-46-31)29(49-17)20-13(36)6-16-19(24(20)41)12(35)5-15(48-16)10-1-3-11(4-2-10)47-32-28(45)25(42)22(39)18(8-34)50-32/h1-6,14,17-18,21-23,25-34,36-45H,7-9H2/t14-,17+,18+,21-,22+,23+,25-,26-,27+,28+,29-,30+,31-,32+/m0/s1
|
| Chemical Name |
6-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4S,5S)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]-5,7-dihydroxy-2-[4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]chromen-4-one
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~172.03 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.08 mg/mL (2.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (2.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3762 mL | 6.8811 mL | 13.7622 mL | |
| 5 mM | 0.2752 mL | 1.3762 mL | 2.7524 mL | |
| 10 mM | 0.1376 mL | 0.6881 mL | 1.3762 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
