Resveratrol

Catalog Number: R001
Chemical Name: trans-3,4′,5-Trihydroxy-trans-stilbene; or 5-[(1E)-2-(4-Hydroxyphenyl)ethenyl]-1,3-benzenediol Botanical Source: Polygonum Cuspidatum Sieb. Root
Molecular Formula: C14H12O3
Molecular Weight: 228.24
CAS Number: 501-36-0
Purity: 98% determined by HPLC.
Appearance: White powder
Melting Temperature: 256 – 257 °C
Storage Temperature: -20°C
Solubility:  0.03 mg/mL in water (warming required)
50 mg/mL in ethanol
16 mg/mL in DMSO
 Other Features: Light sensitive
 Price:

Pharmacological Actions: Resveratrol enhances the activity of the nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase Sirt1 (1), a homologue of a transcriptional silencer in yeast, Sirt1, and modulates the activity of a number of transcriptional regulators in mammals, most notably PGC-1α, a nuclear hormone receptor coactivator that promotes mitochondrial biogenesis in skeletal muscle and brown adipose tissue. Resveratrol improves energy balance and increases mitochondrial function in mice by stimulating the Sirt1-mediated deacetylation of PGC-1α (2,3).

Short-term (15 week) resveratrol treatment protected young (4- to 8-week-old) male mice against obesity induced by a high-fat diet (3) .
Chronic (1+ years) treatment with resveratrol not only improved insulin sensitivity but also increased life span in mice fed a high-fat diet (2).
Resveratrol improves glucose and lipid metabolism specifically in liver (2). It protects mice against development of hepatic steatosis or fatty liver, a condition commonly associated with obesity and insulin resistance (2).

Resveratrol was discovered as a cancer chemopreventive agent in 1997 (4). It selectively suppresses the transcriptional activation of cytochrome P-450 1A1 and inhibits the formation of carcinogen-induced preneoplastic lesions in a mouse mammary organ culture model (5-10). It inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced free radical formation (11), and the formation of TPA-promoted mouse skin tumors in the two-stage model (12). It suppresses the enzymatic activities of COX-1 and -2 (13-15). Resveratrol suppresses the induction of NFκB transcription factor by a number of agents (16-18), and induces apoptosis, cell cycle delay or a block in the G1→ S transition phase in a number of cell lines (19,20).

 References:
 1.        Blander G and Guarente L (2004) The Sir2 Family of Protein Deacetylases. Annu Rev Biochem 73, 417-435.

2.        Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G and Lewis K, et al. (2006) Resveratrol Improves Health and Survival of Mice on A High-calorie Diet. Nature 444, 337-342.

3.        Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P and Elliott  P, et al (2006) Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α. Cell 127,
1109-1122.

4.        Jang M, Cai L, Udeani GO, et al. (1997) Cancer Chemopreventive Activity of Resveratrol, A Natural Product Derived from Grapes. Science 275, 218-220.

5.        Ciolino HP, Daschner PJ and Yeh GC (1998) Resveratrol Inhibits Transcription of CYP1A1 in Vitro by Preventing Activation of the Aryl Hydrocarbon Receptor. Cancer Res 58, 5707-5712.

6.        Ciolino HP and Yeh GC (1999) Inhibition of Aryl Hydrocarbon-induced Cytochrome P-450 1A1 Enzyme Activity and CYP1A1
Expression by Resveratrol. Mol Pharmacol 56, 760-767.

7.        Casper RF, Quesne M, Rogers IM, et al. (1999) Resveratrol Has Antagonist Activity on the Aryl Hydrocarbon Receptor: Implications for Prevention of Dioxin Toxicity. Mol Pharmacol  56, 784-790.

8.        Teel RW and Huynh H (1998) Modulation by Phytochemicals of Cytochrome P450-Linked Enzyme Activity. Cancer Lett 133, 135-141.

9.        Chang TK, Lee WB and Ko HH (2000) Trans-resveratrol Modulates the Catalytic Activity and mRNA Expression of the Procarcinogen-activating Human Cytochrome P450 1B1. Can J Physiol Pharmacol 78, 874-881.

10.       Chan WK and Delucchi AB (2000) Resveratrol, A Red Wine Constituent, Is A Mechanism-based Inactivator of Cytochrome P450 3A4. Life Sci  67, 3103-3112.

11.        Lee SK, Mbwambo ZH, Chung H, et al. (1998) Evaluation of the Antioxidant Potential of Natural Products. Comb Chem High Throughput Screen 1, 35-46.

12.        Bhat KPL and Pezzuto KM (2002) Cancer Chemopreventive Activity of Resveratrol. Ann NY Acad Sciences 957, 210-229.

13.        Kimura Y, Okuda H and Arichi S (1985) Effects of Stilbenes on Arachidonate Metabolism in Leukocytes. Biochim Biophys Acta 834, 275-278.

14.        Subbaramaiah K, Chung WJ, Michaluart P, et al. (1998) Resveratrol Inhibits Cyclooxygenase-2 Transcription and Activity in
Phorbol Ester-treated Human Mammary Epithelial Cells. J Biol Chem 273, 21875-21882.

15.        Mutoh M, Takahashi M, Fukuda K, et al. (2000) Suppression of Cyclooxygenase-2 Promoter-dependent Transcriptional Activity in Colon Cancer Cells by Chemopreventive Agants with A Resorcin-type Structure. Carcinogenesis 21, 959-963.

16.        Manna SK, Mukhopadhyay A and Aggarwal BB (2000) Resveratrol Suppresses TNF-induced Activation of Nuclear Transcription Factors NF-κB, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation. J Immunol 164, 6509-6519.

17.        Draczynska-Lusiak B, Chen YM and Sun AY (1998) Oxidized Lipoproteins Activate NF-kappaB Binding Activity and Apoptosis in PC12 cells. Neuroreport Neuroreport 9, 527-532.

18.        Holmes-McNary M and Baldwin AS Jr (2000) Chemopreventive Properties of Trans-resveratrol Are Associated with Inhibition of Activation of the IkappaB Kinase. Cancer Res 60, 3477-3483.

19.        Carbo N, Costelli P, Baccino MF, et al. (1999) Resveratrol, A Natural Product Present in Wine, Decreases Tumor Growth in A Rat Tumor Model. Biochem Biophys Res Commun 54, 739-743.

20.        Zou J, Huang Y, Chen Q, et al. (1999) Suppression of Mitogenesis and Regulation of Cell Cycle Traverse by Resveratrol in Cultured Smooth Muscle Cells. Int J Oncol 15, 647-651.