Vitisin A has antioxidant, anticancer, antiapoptotic, neuro-protection, and anti-inflammatory effects. Vitisin A inhibits LPS-induced NO and iNOS production by downregulating ERK1/2 and p38 and NF-κB signaling pathways. Vitisin A also inhibits adipocyte differentiation. Vitisin A is a resveratrol tetramer extracted from Vitis vinifera roots.

Physicochemical Properties

Molecular Formula	C56H42O12
Molecular Weight	906.93
Exact Mass	906.268
CAS #	142449-89-6
PubChem CID	16131430
Appearance	Typically exists as solid at room temperature
LogP	10.721
Hydrogen Bond Donor Count	10
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	7
Heavy Atom Count	68
Complexity	1680
Defined Atom Stereocenter Count	6
SMILES	OC1C=CC(C2OC3=CC(=CC(/C=C/C4C=CC(O)=C(C5C(C6C=CC(O)=CC=6)C6C(=CC(=CC=6C6C(OC7=CC(=CC5=C67)O)C5C=CC(O)=CC=5)O)O)C=4)=C3C2C2C=C(O)C=C(O)C=2)O)=CC=1
InChi Key	XAXVWWYPKOGXSY-DBHYGPPCSA-N
InChi Code	InChI=1S/C56H42O12/c57-33-10-4-28(5-11-33)49-51(42-23-40(64)26-47-53(42)54(43-22-39(63)24-45(66)52(43)49)56(68-47)30-8-14-35(59)15-9-30)41-17-27(2-16-44(41)65)1-3-31-18-38(62)25-46-48(31)50(32-19-36(60)21-37(61)20-32)55(67-46)29-6-12-34(58)13-7-29/h1-26,49-51,54-66H/b3-1+/t49-,50+,51+,54+,55-,56-/m1/s1
Chemical Name	(1S,8S,9R,16S)-9-[5-[(E)-2-[(2S,3S)-3-(3,5-dihydroxyphenyl)-6-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-1-benzofuran-4-yl]ethenyl]-2-hydroxyphenyl]-8,16-bis(4-hydroxyphenyl)-15-oxatetracyclo[8.6.1.02,7.014,17]heptadeca-2(7),3,5,10(17),11,13-hexaene-4,6,12-triol
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
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Vitisin A inhibits nitric oxide (NO) production and inducible NO synthase (iNOS) expression in LPS-induced RAW 264.7 macrophage cells; specific IC50, Ki, or EC50 values are not provided[1]. Neuronal cells, specifically through modulation of BDNF-CREB signaling pathway;
ln Vitro	Vitisin A dose-dependently inhibited LPS-induced NO production and iNOS expression in RAW 264.7 macrophage cells. It also suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 phosphorylation, as well as NF-κB activation, suggesting that Vitisin A decreases NO production via downregulation of the ERK1/2, p38, and NF-κB signaling pathways[1]. Vitisin A, a resveratrol tetramer isolated from Vitis vinifera roots, exhibits antioxidative, anticancer, antiapoptotic, and anti-inflammatory effects. It also inhibits nitric oxide (NO) production. Here, we examined the mechanism by which vitisin A inhibits NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. Vitisin A dose dependently inhibited LPS-induced NO production and inducible NO synthase (iNOS) expression. In contrast, the production of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was not altered by vitisin A. To investigate the signaling pathway for NO inhibition by vitisin A, we examined nuclear factor-kappaB (NF-kappaB) activation in the mitogen-activated protein kinase (MAPK) pathway, an inflammation-induced signal pathway in RAW 264.7 cells. Vitisin A inhibited LPS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 phosphorylation and suppressed LPS-induced NF-kappaB activation in RAW 264.7 cells. This suggests that vitisin A decreased NO production via downregulation of ERK1/2 and p38 and the NF-kappaB signal pathway in RAW 264.7 cells. [1] . Inhibition of adipocyte differentiation is one approach among the anti-obesity strategies. This study demonstrates that vitisin A, a resveratrol tetramer, inhibits adipocyte differentiation most effectively of 18 stilbenes tested. Fat accumulation and PPARgamma expression were decreased by vitisin A in a dose-dependent manner. Vitisin A significantly inhibited preadipocyte proliferation and consequent differentiation within the first 2 days of treatment, indicating that the anti-adipogenic effect of vitisin A was derived from anti-proliferation. Based on cell cycle analysis, vitisin A blocked the cell cycle at the G1-S phase transition, causing cells to remain in the preadipocyte state. Vitisin A increased p21 expression, while the Rb phosphorylation level was reduced. Therefore, vitisin A seems to induce G1 arrest through p21- and consequent Rb-dependent suppression of transcription. On the other hand, ERK and Akt signaling pathways were not involved in the anti-mitotic regulation by vitisin A. Taken together, these results suggest that vitisin A inhibits adipocyte differentiation through preadipocyte cell cycle arrest[2]. Neuroprotection: Vitisin A exhibited neuroprotective effects in a human neuroblastoma cell line (SH-SY5Y) by increasing cell viability in a dose-dependent manner. At 5 μM and 100 μM, vitisin A significantly elevated cell viability by 10% and 20%, respectively, compared to the control group. When co-treated with H2O2, which reduced cell viability, vitisin A at 100 μM almost fully reversed this effect. [3] Long-term Potentiation (LTP): In ex vivo experiments, vitisin A protected against scopolamine-induced impairment of LTP in the hippocampal CA3-CA1 synapse, indicating restoration of synaptic mechanisms of learning and memory. [3]
ln Vivo	Neurodegenerative disorders, such as Alzheimer's disease (AD), are characterized by cognitive function loss and progressive memory impairment. Vitis vinifera, which is consumed in the form of fruits and wines in various countries, contains several dietary stilbenoids that have beneficial effects on neuronal disorders related to cognitive impairment. However, few studies have investigated the hypothalamic effects of vitisin A, a resveratrol tetramer derived from V. vinifera stembark, on cognitive functions and related signaling pathways. In this study, we conducted in vitro, ex vivo, and in vivo experiments with multiple biochemical and molecular analyses to investigate its pharmaceutical effects on cognitive functions. Treatment with vitisin A increased cell viability and cell survival under H2O2-exposed conditions in a neuronal SH-SY5 cell line. Ex vivo experiments showed that vitisin A treatment restored the scopolamine-induced disruption of long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse, indicating the restoration of synaptic mechanisms of learning and memory. Consistently, central administration of vitisin A ameliorated scopolamine-induced disruptions of cognitive and memory functions in C57BL/6 mice, as evidenced by Y-maze and passive avoidance tests. Further studies showed that vitisin A upregulates BDNF-CREB signaling in the hippocampus. Together, our findings suggest that vitisin A exhibits neuroprotective effects, at least partially, by upregulating BDNF-CREB signaling and LTP [3]. Cognitive and Memory Functions: Central administration of vitisin A ameliorated scopolamine-induced disruptions of cognitive and memory functions in C57BL/6 mice, as evidenced by improvements in Y-maze and passive avoidance tests. [3] BDNF-CREB Signaling: Vitisin A upregulated BDNF-CREB signaling in the hippocampus of mice, as shown by increased mRNA expression levels of BDNF and its downstream genes (TrkB, AKT, CREB, and CaMKII). [3]
Cell Assay	RAW 264.7 macrophage cells were treated with LPS to induce NO production and iNOS expression. Various concentrations of Vitisin A were then added to assess its effect on NO production and signaling pathways. Western blot analysis was performed to evaluate the expression levels of iNOS and phosphorylation of ERK1/2, p38, and NF-κB[1]. MTT Assay: SH-SY5Y cells were treated with vitisin A at various concentrations (0, 1, 5, or 100 μM) for 24 hours, followed by MTT assay to measure cell viability. [3]
Animal Protocol	Drug Administration: Vitisin A was dissolved in PBS and administered via cannulas into the third ventricle of the brain of C57BL/6 mice at doses of 1 ng or 100 ng three times a week for one month. [3] Behavioral Tests: After one month of vitisin A administration, mice were tested for cognitive and memory functions using Y-maze and passive avoidance tests. Scopolamine was injected intraperitoneally 30 minutes before each test to induce cognitive impairment. [3]
References	[1]. Vitisin A suppresses LPS-induced NO production by inhibiting ERK, p38, and NF-kappaB activation in RAW 264.7 cells. Int Immunopharmacol. 2009 Mar;9(3):319-23. [2]. Vitisin A inhibits adipocyte differentiation through cell cycle arrest in 3T3-L1 cells. Biochem Biophys Res Commun. 2008 Jul 18;372(1):108-13. [3]. The central administration of vitisin a, extracted from Vitis vinifera, improves cognitive function and related signaling pathways in a scopolamine-induced dementia model. Biomed Pharmacother. 2023 Jul;163:114812.
Additional Infomation	Vitisin A is a member of benzofurans. Vitisin A has been reported in Vitis flexuosa, Vitis davidii, and other organisms with data available. Vitisin A is a metabolite found in or produced by Saccharomyces cerevisiae. Vitisin A is a resveratrol tetramer isolated from Vitis vinifera roots. It exhibits antioxidative, anticancer, antiapoptotic, and anti-inflammatory effects. This study focused on the mechanism by which Vitisin A inhibits LPS-induced NO production in RAW 264.7 macrophage cells[1]. Background: Vitisin A is a resveratrol tetramer isolated from Vitis vinifera stembark. Previous studies have shown its anti-inflammatory, neuroprotective, and anti-cholesterolemic activities. [3] Mechanism of Action: Vitisin A is proposed to exert its neuroprotective effects by upregulating the BDNF-CREB signaling pathway, which is crucial for synaptic plasticity and cognitive function. [3]

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.1026 mL	5.5131 mL	11.0262 mL
	5 mM	0.2205 mL	1.1026 mL	2.2052 mL
	10 mM	0.1103 mL	0.5513 mL	1.1026 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.