Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention

Abstract

Resveratrol, (3,4’,5-trihydroxystilbene) has long been suspected to show a broad range of biological activities of medicinal interest such as anticancer, anti-oxidative, anti-diabetic, anti-aging and anti-inflammatory activities. Piceatannol (3,3’,4’,5-tetrahydroxystilbene) is a hydroxylated analogue of resveratrol and it confirms a lot of similar biological activities as shown by resveratrol. Both resveratrol and piceatannol are very important naturally occurring polyphenolic stilbenes, produced by plants in response to fungal infection, mechanical damage, or ultra-violet irradiation. They can be consumed on a daily basis as they show no harmful effects on human body. They play a significant role in improving human health. Compared with resveratrol, piceatannol is a more potent anticancer agent and preferable agent with other biological activities like antioxidant activity. This article reports biological activities of the two important stilbenes: resveratrol and piceatannol and their possible role in disease prevention.

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Research Article Open Access
Kukreja et al., J Blood Disorders Transf 2014, 5:9
http://dx.doi.org/10.4172/2155-9864.1000240
Review Article Open Access
Blood
Disorders & Transfusion
Volume 5 • Issue 9 • 1000240
J Blood Disorders Transf
ISSN: 2155-9864 JBDT, an open access journal
Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention
Aayush Kukreja1*, Neha Wadhwa2 and Archana Tiwari1
1School of Biotechnology, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal, India
2Department of Biotechnology, College of Professional Studies, SR Group of Institutions, Bhopal, India
*Corresponding aut hor: Aayush Kukreja, School of Biotechnology, Rajiv Gandhi
Proudyogiki Vishwavidyalaya, Airport Road-Bhopal-462033 Madhya Pradesh, India,
Tel: 0755-2678873; Fax: 0755-2742006; E-mail: aayush_kukreja@yahoo.co.in
Received September 29, 2014; Accepted November 29, 2014; Published
December 05, 2014
Citation: Kukreja A, Wadhwa N, Tiwari A (2014) Therapeutic Role of Resveratrol
and Piceatannol in Disease Prevention. J Blood Disorders Transf 5: 240. doi:
10.4172/2155-9864.1000240
Copyright: © 2014 Kukreja A, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits un-
restricted use, distribution, and reproduction in any medium, provided the original
author and source are credited.
Keywords: Resveratrol; Piceatannol; Polyphenols; Biological
activities
Introduction
Polyphenols are abundant micronutrients that complement and
add to the functions of antioxidants, vitamins and enzymes as a defense
against oxidative stress caused by excess reactive oxygen species. ey
contain phenolic rings in their structure and are found in dierent forms
in nature. ese compounds are classied into dierent groups on the
basis of the number of phenol rings that they contain and structural
elements that are attached to these rings (Figure 1) [1,2].
Resveratrol is the most well characterized stilbenes, having a
trihydroxystilbene skeleton [3,4]. Piceatannol closely resembles
resveratrol in structure [5]. Both piceatannol and resveratrol possess
almost similar biological activities like antioxidant, antiproliferative and
anti-inammatory properties [6]. e importance of these compounds
in disease prevention has been reviewed here.
Resveratrol
Resveratrol (3,4’,5-trihydroxystilbene) is a natural stilbene
containing two aromatic rings in its structure. It is a phytoalexin formed
naturally by 72 dierent plant species, especially pine trees, jackfruit,
mulberry, blueberry, cranberry, grape vines and legumes (Figure 2). It is
found in large amount in peanuts, soybeans and pomegranates [7-10].
Resveratrol exists in two isomeric forms: cis-resveratrol and trans-
resveratrol. e trans form is more stable and potent than the cis form.
Molecular structure of resveratrol consists of two aromatic rings that
are linked together by a methylene double bond (Figure 3) [8].
All the three hydroxyl groups of resveratrol are responsible for
intensive hydrogen-bonding network [10]. Its biological activity is
dependent on the presence of intramolecular hydrogen bonding, double
bond and number and position of hydroxyl groups [11]. Resveratrol
is a fat soluble plant secondary metabolite produced with the help of
enzyme stilbene synthetase [12]. It is known to possess good cancer
chemo preventive properties [10].
Biological Activities of Resveratrol
Resveratrol has many biological roles and dierent mechanisms of
action [13]. It can inhibit the progression of several diseases, including
cardiovascular disease, carcinogenic, neurodegenerative, and prevent
aging process. Resveratrol has found to possess anti-inammatory,
antioxidant and antimicrobial properties [9,13].
Resveratrol as an antioxidant
Recognition of resveratrol as a natural antioxidant agent was
illustrated by Zini et al. [14,15]. Resveratrol possesses both antioxidant
and free radical scavenging activity. It increases the activities of
antioxidant enzymes such as glutathione peroxidase, SOD (superoxide
Abstract
Resveratrol, (3,4’,5-trihydroxystilbene) has long been suspected to show a broad range of biological activities
of medicinal interest such as anticancer, anti-oxidative, anti-diabetic, anti-aging and anti-inammatory activities.
Piceatannol (3,3’,4’,5-tetrahydroxystilbene) is a hydroxylated analogue of resveratrol and it conrms a lot of
similar biological activities as shown by resveratrol. Both resveratrol and piceatannol are very important naturally
occurring polyphenolic stilbenes, produced by plants in response to fungal infection, mechanical damage, or
ultra-violet irradiation. They can be consumed on a daily basis as they show no harmful effects on human body.
They play a signicant role in improving human health. Compared with resveratrol, piceatannol is a more potent
anticancer agent and preferable agent with other biological activities like antioxidant activity. This article reports
biological activities of the two important stilbenes: resveratrol and piceatannol and their possible role in disease
prevention.
Figure 1: Classication of polyphenols.

Citation: Kukreja A, Wadhwa N, Tiwari A (2014) Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention. J Blood Disorders Transf 5:
240. doi: 10.4172/2155-9864.1000240
Page 2 of 6
Volume 5 • Issue 9 • 1000240
J Blood Disorders Transf
ISSN: 2155-9864 JBDT, an open access journal
dismutase), catalase, and glutathione reductase [16]. It also maintains
the level of intracellular antioxidants in the biological systems [15].
Resveratrol as an anticancer agent
Resveratrol is a good anticancer agent known since ages [11].
It inhibits onset and promotion of cancer. It promotes anti-tumoral
activity by inhibiting angiogenesis [17,18]. e anti-cancer eect of
resveratrol is associated with the damage of mitochondrial function
that leads to an increase in ROS (reactive oxygen species), apoptosis
and possibly intracellular drug accumulation via inhibition of proteins
involved in MDR (multi-drug resistance) [19].
Resveratrol as an anti-inammatory agent
Resveratrol exhibits anti-inammatory activity through modulation
of enzymes and pathways that are mostly centered on cyclooxygenases
COX-1 and COX-2. It also suppresses the activity of NF-kB (nuclear
factor kappa light chain enhancer of activated B cells) and I-kB
(inhibitor of kappa) kinase and reduced production of prostaglandin
E2 (PGE2) and ROS in lipopolysaccharide (LPS) -activated microglial
cells [20,21].
Resveratrol as an anti-microbial agent
Resveratrol possesses antimicrobial properties. It inhibits the
growth of some pathogenic microorganism such as gram-positive and
gram-negative bacteria and fungi like Aspergillus niger, Helicobacter
pylori, Aspergillus avus, Candida albicans, Staphylococcus aureus,
Escherichia coli and Pseudomonas aeruginosa [13]. It inhibits the
growth of Escherichia coli via site-specic oxidative damage to the cell
membrane [14]. Resveratrol is a potent antimicrobial agent and may
be used in future for the treatment of infections caused by certain
pathogens [22,23].
Resveratrol as an anti-aging agent
Resveratrol possesses anti-aging activity. Its anti-aging activity
was seen on yeast (Saccharomyces cerevisiae), fruit y (Drosophila
melanogaster) and round worm (Caenorhabditis elegans). Resveratrol
increases genetic expression of SIR2 enzyme, NAD-dependent, sirutuin
class of deacetylase resulting in an increase in the life time of these
species [24].
Resveratrol in cardiovascular protection
Resveratrol possesses cardioprotective eects as it inhibits platelet
aggregation, thromboxane A2 formation (vasodilator eect) and
peroxidase reactions of Cox-1 [25]. It has been observed that even low
doses (such as consumed in the common diet) of resveratrol shows
cardio-protective activity [26].
Resveratrol in cancer prevention
Resveratrol has been reported to inhibit the proliferation of tumors
of breast, colon and prostate cancer. Various mechanisms for the
anticancer action of resveratrol include angiogenesis inhibition, cell
cycle alteration, apoptosis and antioxidant eects. It also suppresses
cytochrome P450 that is considered as procarcinogens [18,25].
Resveratrol in neurological disorder
Resveratrol is a neuroprotective supplement for neurological
disorders like Alzheimer’s disease, Parkinson disease and Huntingtons
disease. It reduces the level of neuronal cell death. It represses p53,
thereby preventing neurons from oxidative damage [25].
Resveratrol in thalassemia
Resveratrol possesses both anti-oxidant and HbF (fetal hemoglobin)
inducing properties. It activates gamma (γ) -globin genes expression
and helps in the production of HbF. is property of resveratrol is
helpful in the treatment of beta thalassemia [27].
Resveratrol in diabetes
Resveratrol has been hypothesized to protect β cells in diabetes. It
has experimentally proved that resveratrol lowers the insulin secretion
in blood. Its inhibitory eect has been proved in hyperinsulinemic
animals [28]. Resveratrol shields against hepatic and renal impairment
in the diabetic patients [29]. is indicates that resveratrol has benecial
role in the prevention and treatment of diabetes [28].
Piceatannol
Piceatannol (3,3’,4’,5-tetrahydroxystilbene) is a naturally occurring
hydroxylated analog of resveratrol (Figure 4). It has two phenol rings
that are linked together by a styrene double bond. It exists in two
isomeric forms: cis- piceatannol and trans- piceatannol. Usually, its
trans isomeric form is more stable as compared to cis form [6,30,31].
It has been identied in various plants specically in passion
fruit (Passiora edulis), Cassia marginata, Melaleuca leucadendron,
Figure 2: Sources of resveratrol.
Figure 3: Chemical structure of resveratrol.

Citation: Kukreja A, Wadhwa N, Tiwari A (2014) Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention. J Blood Disorders Transf 5:
240. doi: 10.4172/2155-9864.1000240
Page 3 of 6
Volume 5 • Issue 9 • 1000240
J Blood Disorders Transf
ISSN: 2155-9864 JBDT, an open access journal
Asian legume (Cassia garrettiana), Rhubarb (Rheum spp.), Euphorbia
lagascae, Mezoneuron cucullatum, Vitis amurensis, Caragana tibetica,
Rheum rhaponticum, Partneocissus tricuspidata, Aiphanes aculeata,
Arachis hypogaea, Vitis thunbergii, Ampelopsis brevipedunculaata and
Vaccinium berries (Figure 5) [6].
Rhodomyrtus tomentosa also known as Sim fruit has been reported
to contain 1000-2000 times higher piceatannol than that found in
red grape [32]. In humans, resveratrol metabolism in the presence of
enzyme CYP1B1 (Cytochrome P450 1B1) produces piceatannol as a
major metabolite (Figure 6) [8].
Biological Activities of Piceatannol
Like resveratrol, piceatannol also has many biological roles and
dierent mechanisms of action. It possesses biological activities like
anticancer, antioxidant, antileukaemic and anti-inammatory activities.
It also possesses property to combat diseases like breast cancer, prostate
cancer, colon cancer, leukemia, lymphoma and melanoma [6].
Piceatannol as an antioxidant agent
e antioxidant activity of piceatannol is due to hydroxyl groups in
its stilbene rings. It has good lipid peroxyl radical scavenging activity.
Semiquinone radical of piceatannol is found to be more stable. Its
antioxidant activity was proved by its ability to suppress the production
of melanin in B16 melanoma cells [6,33].
Piceatannol as an anticancer agent
Piceatannol exhibits anticancer activity due to its potential to
inhibit spread of a vast array of dierent tumor cells, including
lymphoma, leukaemia, breast cancer, prostate cancer, and colon cancer.
It shows growth inhibition and the proapoptic eect on cancer cells.
Its proapoptic eect may be due to loss of mitochondrial potential,
activation of caspases and release of cytochrome C [6].
Its proapoptic activity has been observed in various cancer cells
including skin, prostate, bladder and breast. It possesses cytotoxicity
activity against prostate cancer cells. It inhibits JAK1 (Janus kinase)
activity proving itself to be curative agent for prostate cancer [6]. In
colon and liver cancer, piceatannol has found to be responsible for
accumulation of cells in G1 and S phase of cell cycle [34]. In bladder
cancer, it has been reported that piceatannol induces apoptosis and
obstructs G0/G1 cells progression [35].
Piceatannol as an antileukaemic agent
Piceatannol exhibits antileukaemic activity as its treatment results
in an increase in Fas and FasL protein expression. It induces death of
human leukaemia cells by increasing intracellular Ca2+ concentration,
activating p38 mitogen activated protein kinase (MAPK), inactivating
extracellular regulated kinase (ERK), producing t-Bid and degrading
procaspase-8 in leukaemic cells [6,36].
Piceatannol results in apoptosis, DNA fragmentation, decreased
Bcl-2 and cIAP-2 (anti- apoptic proteins) expression and halt of cells
in sub G1 phase. Up-regulation of Fas/FasL has been reported in
piceatannol treated leukaemic cells [5,37].
Piceatannol as an anti-inammatory agent
Piceatannol shows anti-allergic inammatory activity by regulating
MAPK signaling pathway. It suppresses SyK activity by obstructing
FcεR I-mediated signaling in mast cells [6,38].
Piceatannol as an anti-adipogenic agent
Piceatannol plays a vital role in inhibiting adipogenesis. It
downregulates C/EBP and PPAR (pro-adipogenic transcription factors)
expression. It also inhibits phosphorylation and kinase activity of
signaling pathways including IR and PI3K/Akt pathway [39].
Piceatannol as an antimelanogenic agent
Picetannol upregulates intracellular GSH level and downregulates
GSSG level in B16 cells. It increases GSH/GSSG ratio resulting in an
increase in intracellular reducing power, which plays a pivotal role in
the regulation of melanogenesis. It lowers melanin content without
exhibiting any antagonist eect on cell viability [40].
Figure 4: Chemical structure of piceatannol.
Figure 5: Sources of piceatannol.
Figure 6: Resveratrol metabolism in humans.

Citation: Kukreja A, Wadhwa N, Tiwari A (2014) Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention. J Blood Disorders Transf 5:
240. doi: 10.4172/2155-9864.1000240
Page 4 of 6
Volume 5 • Issue 9 • 1000240
J Blood Disorders Transf
ISSN: 2155-9864 JBDT, an open access journal
Piceatannol in diabetes
Piceatannol exhibits antidiabetic phytochemical activity. It enhances
glucose uptake, AMPK phosphorylation and glucose transporter 4
(GLUT4) translocation to overcome insulin resistance in diabetic cells.
erefore, it plays a therapeutic role in the prevention of type 2 diabetes
[6,41].
Piceatannol in asthma
Piceatannol, a Syk-selective tyrosine kinase possesses signicant
inhibitory eect in the release of histamine and peptidoleukotriene
from sensitized lung fragments. Syk kinase is an essential upstream
signaling molecule which activates various inammatory cells like T
cells, B cells and monocytes. Its inhibition in inammatory cell may
prove to be benecial in the treatment of asthma [42,43].
Piceatannol in bone formation
Piceatannol induces dierentiation of osteoblasts from its
progenitor stage to well dierentiated osteoblasts. It induces BMP-2
(bone morphogenetic protein-2) expression which increases alkaline
phosphatase and osteocalcin production in the cells. Piceatannol
stimulates BMP2-BMP receptor interaction which is linked with
the production of BMP-2. erefore, piceatannol may be useful in
stimulating osteoblastic activity, which results in bone formation [44].
Biological spectrum of piceatannol and resveratrol
Piceatannol and resveratrol both belong to stilbene family.
ey both can be synthesized by using Perkin’s approach, using
3,5-dihydoxyacetophenone as a starting material [45]. ey share
almost same biological activities such as antioxidant, anti-inammatory,
anticancer and antileukaemic activities (Table 1) [6].
Piceatannol in Alzheimer
Alzheimer’s disease is prevalent neurodegenerative disease in the
elderly people, which eventually lead to death of person suering
from this disease. Studies have shown a relationship between the
consumption of polyphenol rich foods or drinks and the prevention of
Alzheimer’s disease. e results of a recent study provides evidence that
piceatannol have high potential to prevent Alzheimer’s disease [46].
Piceatannol in Cardiovascular Diseases
e frequency of cardiovascular diseases is high in developing and
developed countries. Cardiovascular diseases are responsible for high
rate of mortality. Many drugs are available for treating cardiovascular
diseases and complications associated with it. Intake of functional
foods or dietary supplements for treating cardiovascular diseases has
gained wide acceptance by the general public. Piceatannol is believed to
be eective in preventing cardiovascular diseases such as arrhythmia,
hypercholesterolemia, angiogenesis and atherosclerosis [47].
Pretreatment with piceatannol suppresses cardiac hypertrophy
which has been assessed by expression level of hypertrophy markers,
cross-sectional area and heart weight/body weight ratio. It also inhibits
cardiac hypertrophy induced by lentiviral GATA-6 [48].
Piceatannol in reducing toxic eect of neutrophils
Piceatannol has ability to reduce the toxic eect produced by
neutrophils. It elevates the percentage of early apoptotic neutrophils
and hinders the activity of protein kinase C which is the main regulatory
enzyme in neutrophils. e result indicates that piceatannol may be
used as a complementary medicine in lowering the level of activated
neutrophils [49].
Comparative Biological Properties of Piceatannol and
Resveratrol
Piceatannol is a more active resveratrol analogue due to the presence
of additional hydroxyl group at 3’ position (Table 2). It possesses
stronger anticancer activity than resveratrol [6]. Piceatannol possesses
higher ability to scavenge free radicals as compared to resveratrol
[50]. e presence of an extra hydroxyl group in piceatannol makes it
reactive and more potent antioxidant as compared to resveratrol. e
required concentration of piceatannol to scavenge free radicals is 1200
times lesser than that of resveratrol [6].
Although, resveratrol possesses several benecial eects on human
health as well as in preclusion of many chronic diseases, but its low
Activity Resveratrol Piceatannol
Antioxidant Present Present
Anti-inammatory Present Present
Anticancer Present Present
Antileukaemic Present Present
Table 1: Similar biological activities of resveratrol and piceatannol [11,14-
19,29,32,33,36].
Compound
Position on the ring
3 4 5 3’ 4’ 5’
Resveratrol OH - OH - OH -
Piceatannol OH - OH OH OH -
Table 2: Table showing hydroxyl group positions in resveratrol and piceatannol [6].
Parameters Piceatannol Resveratrol
Nomenclature 3,3′,4′,5-trans-
trihydroxystilbene
3,4′,5-trans-
trihydroxystilbene
Spectrophotometric
analysis in ethanol
Absorbs maximally at
322 nm
Absorbs maximally at
308 nm.
Content in grapes About 4-times lower than
resveratrol
about 4-times higher
than piceatannol
Inhibitory activity Does not inhibit CYP2E1
(Cytochrome P450 2E1)
Inhibits CYP2E1
(Cytochrome P450 2E1)
Scavenging activity
Show stronger activity to
scavenge free radicals.
Higher rate constant of
reaction with linoleate
(LOO•)
Concentration of
piceatannol required to
scavenge O2
•- is 1200
times lower than that of
Resveratrol
Lower rate constant of
reaction with linoleate
(LOO•)
Substrate of
enzyme catechol-O-
methyltransferase
(COMT)
Substrate of
enzyme catechol-O-
methyltransferase (COMT)
due to presence of extra
3’-OH group
Not a substrate of
enzyme catechol-O-
methyltransferase
(COMT)
Inhibition of MRP1-
mediated transport of
2′,7′-bis-(carboxypropyl)-
5(6)-carboxyuorescein
(BCPCF) from
human erythrocytes
Show moderate activity Ineffective
Hormetic effect
Piceatannol-induced
hormetic response has
been reported
Not reported till now
TPA-induced NFkB DNA
binding
Inhibits NFkB DNA binding
to a greater extent
inhibits NFkB DNA
binding to a lesser extent
Table 3: Table showing distinction between piceatannol and resveratrol [6,15,18,25].

Citation: Kukreja A, Wadhwa N, Tiwari A (2014) Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention. J Blood Disorders Transf 5:
240. doi: 10.4172/2155-9864.1000240
Page 5 of 6
Volume 5 • Issue 9 • 1000240
J Blood Disorders Transf
ISSN: 2155-9864 JBDT, an open access journal
bioavailability and rapid metabolism limits its use in the preclusion of
chronic diseases [8]. Table 3 illustrates dissimilarity between resveratrol
and piceatannol.
Piceatannol has much more eective biological activity and
bioavailability as compared to resveratrol. erefore, piceatannol is
gaining more scientic attention than resveratrol for improving health
related diseases. But more studies are needed to prove its eective
diseases saving properties [8,38].
Conclusions
Resveratrol and piceatannol are naturally occurring polyphenolic
compounds with a wide range of biological activities. Resveratrol
plays a signicant role in prevention of diseases, but due to its fast
metabolism in the body and poor bioavailability, it is less preferred.
Piceatannol being a natural analogue of resveratrol, contains additional
hydroxyl group which confers to its more eective biological activities
as compared to resveratrol. In order to make both of these compounds
applicable for clinical use, they should be studied more extensively to
understand their bioavailability, metabolic pathways and toxicity in
humans.
References
1. Tsao R (2010) Chemistry and biochemistry of dietary polyphenols. Nutrients
2: 1231-1246.
2. Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L (2004) Polyphenols:
food sources and bioavailability. Am J Clin Nutr 79: 727-747.
3. Han X, Shen T, Lou H (2007) Dietary Polyphenols and Their Biological
Signicance. Int J Mol Sci. 8: 950-88.
4. Bavaresco L, Fregoni M, Trevisan M, Mattivi F, Vrhovsek U, et al. (2002) The
occurrence of the stilbene piceatannol in grapes. Vitis 41: 133-136.
5. Potter GA, Patterson LH, Wanogho E, Perry PJ, Butler PC, et al. (2002) The
cancer preventative agent resveratrol is converted to the anticancer agent
piceatannol by the cytochrome P450 enzyme CYP1B1. Br J Cancer. 86: 774-
778.
6. Piotrowska H, Kucinska M, Murias M (2012) Biological activity of piceatannol:
leaving the shadow of resveratrol. Mutat Res 750: 60-82.
7. Kukreja A, Wadhwa N, Tiwari A (2013) Therapeutic role of natural agents in
beta-thalassemia: A review. Journal of Pharmacy Research 6: 954-959.
8. Catalgol B, Batirel S, Taga Y, Ozer NK (2012) Resveratrol: French paradox
revisited. Front Pharmacol 3: 141.
9. Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo
evidence. Nat Rev Drug Discov 5: 493-506.
10. Drábiková K, Perečko T, Nosáľ R, Harmatha J, Smidrkal J, et al. (2012)
Polyphenol derivatives - potential regulators of neutrophil activity. Interdiscip
Toxicol 5: 65-70.
11. Ovesná Z, Horváthová-Kozics K (2005) Structure-activity relationship of trans-
resveratrol and its analogues. Neoplasma 52: 450-455.
12. Kumar DS, Shankar P, Rao GU (2009) Health benets of resveratrol.
International Journal of Pharmaceutical Sciences and Nanotechnology 2: 407-
412.
13. Paulo L, Oleastro M, Gallardo E, Queiroz JA (2011) Domingues. Antimicrobial
properties of resveratrol: a review, (3rd Edn.) Formatex, pp: 1225-35.
14. Subramanian M, Goswami M, Chakraborty S, Jawali N (2014) Resveratrol
induced inhibition of Escherichia coli proceeds via membrane oxidation and
independent of diffusible reactive oxygen species generation. Redox Biology
2: 865-872.
15. Bonda C, Zhang J, Pavlovic A (2011) The photostability and photostabilization
of trans-resveratrol. Cosmetics and Toiletries magazine 126: 652.
16. de la Lastra CA, Villegas I (2007) Resveratrol as an antioxidant and pro-oxidant
agent: mechanisms and clinical implications. Biochem Soc Trans 35: 1156-
1160.
17. De la Lastra CA, Villegas I, Martin AR (2006) Resveratrol as an antioxidant In:
Aggarwal BB, Shishodia S eds. Resveratrol in health and disease. Washington,
D.C: CRC Press: 33-56.
18. Aluyen JK, Ton QN, Tran T, Yang AE, Gottlieb HB, et al. (2012) Resveratrol:
potential as anticancer agent. J Diet Suppl 9: 45-56.
19. Signorelli P, Ghidoni R (2005) Resveratrol as an anticancer nutrient: molecular
basis, open questions and promises. J Nutr Biochem 16: 449-466.
20. Sun W, Wang W, Kim J, Keng P, Yang S, et al. (2008) Anti-cancer effect of
resveratrol is associated with induction of apoptosis via a mitochondrial
pathway alignment. Adv Exp Med Biol 614: 179-186.
21. Udenigwe CC, Ramprasath VR, Aluko RE, Jones PJ (2008) Potential of
resveratrol in anticancer and anti-inammatory therapy. Nutr Rev 66: 445-454.
22. Kundu JK, Shin YK, Kim SH, Surh YJ (2006) Resveratrol inhibits phorbol ester-
induced expression of COX-2 and activation of NF-kappaB in mouse skin by
blocking IkappaB kinase activity. Carcinogenesis 27: 1465-1474.
23. Chan MM (2002) Antimicrobial effect of resveratrol on dermatophytes and
bacterial pathogens of the skin. Biochem Pharmacol 63: 99-104.
24. (2010) Resveratrol. Monograph. Altern Med Rev 15: 152-158.
25. Markus MA, Morris BJ (2008) Resveratrol in prevention and treatment of
common clinical conditions of aging. Clin Interv Aging 3: 331-339.
26. Kim DH, Ahn T, Jung HC, Pan JG, Yun CH (2009) Generation of the human
metabolite piceatannol from the anticancer-preventive agent resveratrol by
bacterial cytochrome P450 BM3. Drug Metab Dispos. 37: 932-936.
27. Fibach E, Prus E, Bianchi N, Zuccato C, Breveglieri G, et al. (2012) Resveratrol:
Antioxidant activity and induction of fetal hemoglobin in erythroid cells from
normal donors and β-thalassemia patients. Int J Mol Med 29: 974-982.
28. Szkudelski T, Szkudelska K (2011) Anti-diabetic effects of resveratrol. Ann N Y
Acad Sci 1215: 34-39.
29. Schmatz R, Perreira LB, Stefanello N, Mazzanti C, Spanevello R, et al. (2012)
Effects of resveratrol on biomarkers of oxidative stress and on the activity of
delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-
induced diabetic rats. Biochimie 94: 374-383.
30. Kukreja A, Mishra A, Tiwari A (2013) Source, production and biological activities
of piceatannol: a review. IJPSR. 4: 1000-1007.
31. Wolter F, Clausnitzer A, Akoglu B, Stein J (2002) Piceatannol, a natural analog
of resveratrol, inhibits progression through the S phase of the cell cycle in
colorectal cancer cell lines. J Nutr 132: 298-302.
32. Lai TN, Herent MF, Quetin-Leclercq J, Nguyen TB, Rogez H, et al. (2013)
Piceatannol, a potent bioactive stilbene, as major phenolic component in
Rhodomyrtus tomentosa. Food Chem 138: 1421-1430.
33. Wittgen HG, van Kempen LC (2007) Reactive oxygen species in melanoma
and its therapeutic implications. Melanoma Res 17: 400-409.
34. Wolter F, Clausnitzer A, Akoglu B, Stein J (2002) Piceatannol, a natural analog
of resveratrol, inhibits progression through the S phase of the cell cycle in
colorectal cancer cell lines. J Nutr 132: 298-302.
35. Kuo PL, Hus YL (2008) The grape and wine constituent piceatannol inhibits
proliferation of human bladder cancer cells via blocking cell cycle progression
and inducing as/membrane bound Fas ligand-mediated apoptotic pathway. Mol
Nutr Food Res. 52: 408-418.
36. Liu WH, Chang LS (2010) Piceatannol induces Fas and FasL up-regulation in
human leukemia U937 cells via Ca2+/p38alpha MAPK-mediated activation of
c-Jun and ATF-2 pathways. Int J Biochem Cell Biol 42: 1498-1506.
37. Kim YH, Park C, Lee JO, Kim GY, Lee WH, et al. (2008) Induction of apoptosis
by piceatannol in human leukemic U937 cells through down-regulation of Bcl-2
and activation of caspases. Oncol Rep 19: 961-967.
38. Ko YJ, Kim HH, Kim EJ, Katakura Y, Lee WS, et al. (2013) Piceatannol inhibits
mast cell-mediated allergic inammation. Int J Mol Med 31: 951-958.
39. Kwon JY, Seo SG, Heo YS, Yue S, Cheng JX, et al. (2012) Piceatannol, natural
polyphenolic stilbene, inhibits adipogenesis via modulation of mitotic clonal
expansion and insulin receptor-dependent insulin signaling in early phase of
differentiation. J Biol Chem. 287: 11566-78.
40. Yokozawa T, Kim YJ (2007) Piceatannol inhibits melanogenesis by its
antioxidative actions. Biol Pharm Bull 30: 2007-2011.

Citation: Kukreja A, Wadhwa N, Tiwari A (2014) Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention. J Blood Disorders Transf 5:
240. doi: 10.4172/2155-9864.1000240
Page 6 of 6
Volume 5 • Issue 9 • 1000240
J Blood Disorders Transf
ISSN: 2155-9864 JBDT, an open access journal
41. Minakawa M, Miura Y, Yagasaki K (2012) Piceatannol, a resveratrol derivative,
promotes glucose uptake through glucose transporter 4 translocation to plasma
membrane in L6 myocytes and suppresses blood glucose levels in type 2
diabetic model db/db mice. Biochem. Biophys. Res. 422: 469-75.
42. Dustin ML, Chan AC (2000) Signaling takes shape in the immune system. Cell
103: 283-294.
43. Seow CJ, Chue SC, Wong WS (2002) Piceatannol, a Syk-selective tyrosine
kinase inhibitor, attenuated antigen challenge of guinea pig airways in vitro. Eur
J Pharmacol 443: 189-196.
44. Chang JK, Hsu YL, Teng IC, Kuo PL (2006) Piceatannol stimulates osteoblast
differentiation that may be mediated by increased bone morphogenetic
protein-2 production. Eur J Pharmacol 551: 1-9.
45. Sun HY, Xiao CF, Cai YC, Chen Y, Wei W, et al. (2010) Efcient synthesis
of natural polyphenolic stilbenes: resveratrol, piceatannol and oxyresveratrol.
Chem Pharm Bull (Tokyo) 58: 1492-1496.
46. Hassaan Y, Handoussa H, El-Khatib AH, Linscheid MW, El Sayed N, et al.
(2014) Evaluation of plant phenolic metabolites as a source of Alzheimer’s drug
leads. Biomed Res Int 2014: 843263.
47. Tang YL, Chan SW (2014) A review of the pharmacological effects of piceatannol
on cardiovascular diseases. Phytother Res 28: 1581-1588.
48. Kee HJ, Park S, Kang W, Lim KS, Kim JH, et al. (2014) Piceatannol attenuates
cardiac hypertrophy in an animal model through regulation of the expression
and binding of the transcription factor GATA binding factor 6. FEBS Lett 588:
1529-1536.
49. Maraldi T, Vauzour D, Angeloni C (2014) Dietary Polyphenols and Their Effects
on Cell Biochemistry and Pathophysiology. Oxidative medicine and cellular
longevity.
50. Rhayem Y, Thérond P, Camont L, Couturier M, Beaudeux JL, et al. (2008)
Chain-breaking activity of resveratrol and piceatannol in a linoleate micellar
model. Chem Phys Lipids 155: 48-56.
Citation: Kukreja A, Wadhwa N, Tiwari A (2014) Therapeutic Role of Resveratrol
and Piceatannol in Disease Prevention. J Blood Disorders Transf 5: 240. doi:
10.4172/2155-9864.1000240
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