Biomedicine & Pharmacotherapy 95 (2017) 1588–1595

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Biomedicine & Pharmacotherapy

journal homepage: www.elsevier.com/locate/biopha

Review

Comprehensive review on the antimicrobial potency of the plant polyphenol MARK

Resveratrol
Narjess Bostanghadiria, Ali Pormohammada,1, Alireza Salimi Chirania, Ramin Pouriranb,
⁎
Soroor Erfanimaneshc, Ali Hashemia,
a
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
b
School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
c
Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

A R T I C L E I N F O A B S T R A C T

Keywords: Treatment of some infectious diseases are becoming more complicated because of increasing drug resistance rate
Resveratrol and lack of proper antibiotics. Because of the rapid increase in drug-resistance trend, there is an urgent need for
Natural product alternative microbicides to control infectious diseases. Resveratrol (RSV) is a small plant polyphenol that is
Infectious diseases naturally produced and distributed in 72 particular families of plants. The usage of natural derivatives such as
Drug resistance
RSV, have become popular among researchers for curing acute and chronic diseases. The purpose of the preset
study was to comprehensively review and survey the antimicrobial potency of RSV. The present study de-
monstrates RSV as a natural antimicrobial agent.

1. Introduction grandiflorum by M. Takaoka in 1939 [11,12]. Similar to other members

Infectious diseases pertain to be one of the most indispensable
causes of mortality and morbidity world-wide [1]. Evidently, the
treatment of some infectious diseases have become more problematic
and lead to a global dilemma because of the increasing drug resistance
rate and lack of proper antibiotic options. Therefore, the lack of
knowledge regarding the usage of antibiotics, their excessive use in li-
vestock and health care, alteration in some genes; such as mutation,
adaptation or gene expression contributes to the emergence and ex-
pansion of drug resistance [2–4]. Antibiotics are generally indis-
pensable for treating bacterial infections; nonetheless, side effects like
nausea, diarrhea, allergic reactions, and therapeutic interactions are
inevitable [5,6]. As a matter of fact, because of the rapid spread of drug-
resistance, there is an urgent need for alternative microbicides to con-
trol infectious diseases [7]. Scientists are constantly trying to discover
new antibiotics with high antibacterial effects and potency and the
lowest side effects and complications. Natural antibiotics are one of the
primary solutions for the mentioned problems [8]. Specifically among
natural antibiotic, botanical antimicrobial substances have been quite
useful for the treatment of gram positive and negative bacteria [9,10].
Resveratrol (RSV) (3, 5, 4′-trihydroxystilbene) is a stilbenoid compound
(stilbenoids are hydroxylated stilbene derivatives) that was first iso-
lated and characterized from the root of white hellebore, Veratrum
of stilbene family, RSV production is stimulated in response to pa-
thogen, UV-irradiation, and exposure to ozone [13,14]. This compound
is explicitly derived from various plants species, such as grape vines,
pines, berries, legumes and also present with high concentrations in
pomegranates, peanuts and soybeans [15–17]. Resveratrol has been
recognized with a potential role in regulation of immune system and
inflammation, chemoprevention, neuroprotection, cardioprotection
and lipid regulation, as well as treating diseases like diabetes, Parkin-
son's disease and cancer. Besides, RSV has shown antibacterial, antiviral
and antifungal activity [18–25]. The purpose of the present review
article is to focus on the antimicrobial effects of resveratrol. As a matter
of fact, there are reports regarding antibacterial and antifungal potency
of RSV; nevertheless, to the best of our knowledge, this is the first
comprehensive review of Resveratrol antimicrobial potency as a natural
product [26].
2. Structure and derivation of RSV
RSV (3,5,4′-Trihydroxystilbene) is a small plant polyphenol with
228 g/mol molecular weight and 14-carbon skeleton. Furthermore,
stilbene structure consists of precisely two aromatic rings and phenolic
hydroxyl groups with double bonds that makes two cis- and trans- forms
of isomers. However, the cis- resveratrol isomer is unstable and easily

⁎
Corresponding author.
E-mail addresses: pormohammadali@yahoo.com (A. Pormohammad), ali.hashemi@sbmu.ac.ir (A. Hashemi).
1
Equally first author.

http://dx.doi.org/10.1016/j.biopha.2017.09.084
Received 4 June 2017; Received in revised form 14 September 2017; Accepted 18 September 2017
0753-3322/ © 2017 Elsevier Masson SAS. All rights reserved.
N. Bostanghadiri et al.
Fig. 1. Sources of resveratrol, derivatives and their therapeutic effects.
transforms into the trans-form when a reaction occurs with the light
[27] (Fig. 1). Categorically, RSV is soluble in polar solvents such as
ethanol and dimethyl sulfoxide; in contrast, it has poor water solubility
[17,28,29]. RSV is considered as a phytoalexin (antimicrobial and often
antioxidative substances that are synthesized by plants) and has been
utilized in some drug preparations such as darakchasava or manakka
[26]. RSV is naturally produced and distributed in 72 particular fa-
milies of plants including Japanese knotweed, peanuts, grapevines,
pines, different kinds of berries, legumes and grasses, pinus sylvestris
scots, pine, Eucalyptus, Rheom rhaponticum, artocarpus heterophyllus,
syzygium cumini, veratrum grandiflorum, and cassia [30–35].
3. Different analogs, sources and biological effects of RSV
Apart from natural cis and trans isomers, several other natural and
synthetic analogs exist. For instance, piceatannol (trans-3,4,3′,5′-tetra-
hydroxystilbene) which is found in skins of grapes can inhibit tyrosine
kinase activity in lymphoid malignancies. Therefore, in comparison to
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Biomedicine & Pharmacotherapy 95 (2017) 1588–1595
RSV, piceatannol exhibits higher bioactivities as an inhibitor of cy-
clooxygenase 2 and the CSN-associated kinase because of better solu-
bility of piceatannol in H2O. Moreover, it inhibits the activation of p40
and p56 protein tyrosine kinases and NF-kappa B [15,36,37].
Pterostilbene (trans-3, 5-dimethoxy-4-hydroxystilbene) activates
caspases 3/7 and has antioxidant, anti-inflammatory and antic-
arcinogenic activities. Oral administration of this compound to diabetic
rats resulted in attenuated vascular disease and ameliorated diabetes
[38,39]. Another derivative polydatin (resveratrol-3-O-β-mono-D-glu-
coside) has been shown to exert several biological activities including
anti-inflammatory, antioxidant, modulation of β-defensin 2, IL-6 and
IL-8, increasing the gene expression levels of tumor necrosis factor-
alpha, increasing the heat shock protein (Hsp)70B′ gene expression and
decreasing IL-17 production. This derivative additionally demonstrated
numerous protective benefits against myocarditis through dilating
blood vessel, antagonizing platelet aggregation and thrombosis [40].
The oxyresveratrol (trans-2,30,4,50-tetrahydroxystilbene) inhibits ni-
tric oxide (NO), activates NF-κB in macrophages and then reduces
N. Bostanghadiri et al.
edema and decreases prostaglandin E2 production [41].
Additionally, Pinosylvin (3, 5-dihydroxystilbene), an effective an-
tifungal and antimicrobial analogue of RSV, is subsequently secreted
after UV irradiation or microbial attack to the needle and leaves or the
wood of Pinus and Alnus species. Furthermore, pinosylvin may lead to
decrease in concentration of reactive oxygen and nitrogen species in the
blood and is capable to enhance the methotrexate efficacy which can be
useful in arthritis treatment [42].
4. Therapeutic usage of resveratrol
Widely therapeutic uses and health benefits of resveratrol have been
documented. It can also be used as a scaffold to design structural re-
latives potentially able to mediate quite more intense responses with
elevated mechanistic stringency [43]. RSV plays an important role in
alleviating the symptoms of many disorders such as cancer, diabetes
and Parkinson’s disease through its properties like intrinsic anti-oxi-
dant, anti-inflammatory, anti-proliferative and anti-angiogenic effect
[11,44–47] (Fig. 1). Likewise, RSV has been reported as an anti-cancer
natural product by in vitro and in vivo inhibition of tumor cell lines such
as myeloma, breast cancer, lymphoma, colorectal cancer, melanoma,
hepatocellular, pancreatic and prostate carcinoma [48–53]. Recent
studies revealed the effects of RSV on signaling molecules and down-
regulation of angiogenesis associated genes expression [54], activation
of the cell cycle arrest [48] and stimulation of apoptosis [49,51,54]. On
the other hand, RSV sensitizes resistant tumor cell lines to drugs such as
paclitaxel [50], thalidomide and Velcade [49]. The emergence of an-
timicrobial resistance among microbial agents is inevitable and needs
novel strategies to control the resistant pathogens. The usage of natural
products have gained great interest among researchers because of their
medical benefits and fewer side effects [55,56].
5. Anti-viral activity
The antiviral effect of RSV have been shown for hepatitis C virus,
respiratory syncytial virus, herpes simplex virus, varicella zoster virus,
Epstein-Barr virus, influenza virus, human immunodeficiency virus,
human metapneumonia virus, African swine fever virus, enterovirus,
and duck enteritis virus [57–64].
RSV exerts its antiviral effect via different mechanisms such as in-
hibition of viral replication, nucleic acid synthesis, protein synthesis,
and gene expression [65,66] (Table 1).
6. Antifungal activity
RSV has shown great biological activity against various pathogenic
fungi like Pyricularia oryzae, Plasmopara Viticola, Cladosporium cuccu-
merinum, and Sphaeropsis sapinea [67]. In contrary to its antimicrobial
effects, the antifungal activity and its mechanism are still not known.
Antifungal activity of RSV has been tested on Candida albicans in which
RSV could penetrate into the cell without fatal activity on the cell
membrane and induce apoptosis through activated metacaspase and
promoted cytochrome c release in C. albicans at low concentrations
[68]. In the other study conducted by Collado, it was revealed that RSV
did not have any effect on the exponential growth phase of C. albicans in
common dosages (10–40 μg/ml and at 400 μg/ml) [69].
7. Antiparasitic activity
Antiparasitic activity of this polyphenol compound has been eval-
uated against Leishmania amazonensis, Setaria cervi, and Trypanosoma
cruzi. In Leishmania amazonensism RSV exhibited both antipromastigote
and antiamastigote effects, increased the percentage of promastigotes,
reduced the mitochondrial potential and decreased the activity of the
arginase enzyme in macrophages that lead to elimination of parasites
[70]. The outcomes of another study demonstrated that trans- RSV
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Biomedicine & Pharmacotherapy 95 (2017) 1588–1595
analogs have anti-Leishmania amazonensis activity and induce promas-
tigotes adventitious death [41]. In filarial nematode Setaria cervi trans-
stilbene derivatives exerted antifilarial activity through generation of
ROS and mediating apoptosis [71]. RSV showed strong anti-parasitic
effects against Trypanosoma cruzi via promoted metacyclogenesis, re-
duced epimastigotes growth, blocked differentiation and/or replication
of intracellular amastigotes [72].
8. Antibacterial activity
The antibacterial effects of RSV has been demonstrated in gram
positive and gram negative bacteria such as Escherichia coli O157:H7
[73], Salmonella Typhimurium [74], Listeria monocytogenes [75], Sta-
phylococcus aureus [76], Vibrio cholerae [74], Actinobacillus actinomyce-
temcomitans [77], Porphyromonas gingivalis [77], Ralstonia solanacearum
[10], Propionibacterium acnes [78], Pseudomonas aeruginosa [79], Cam-
pylobacter jejuni [80], Chlamydia pneumoniae [81], Haemophilus ducreyi
[82], Helicobacter pylori [83], Proteus mirabilis [84], Mycobacterium tu-
berculosis [85], methicillin-resistant Staphylococcus aureus (MRSA)[86],
vancomycin-resistant Enterococcus (VRE) [85], Xylella fastidiosa [87],
Enterobacter aerogenes [88], Klebsiella pneumoniae [89], Enterobacter
cloacae [77], Providencia stuartii [88], Arcobacter cryaerophilus [85,90],
Arcobacter butzleri [90], Salmonella enterica serovar Typhimurium [91],
Salmonella enterica serovar Enteritidis [92], Bacillus megaterium [91],
Bacillus subtilis [93] Bacillus cereus [89] and Enterococcus faecal [89].
Consequently, effects of RSV on various processes such as biofilm for-
mation, motility and quorum sensing will be presented for selected
bacterial species. It exhibits remarkable versatility in its strategies for
killing bacteria and inhibits various vital bacterial behaviors such as
motility, adhesion, quorum sensing, biofilm formation, flagellar gene
expression and hemolytic activity [10,76,94,95].
A number of studies reported RSV has bacteriostatic activity rather
than bactericidal activity [96], in contrast some others found that this
compound has bactericidal in addition to its bacteriostatic effect [82].
Evidence of laboratory models suggest that these infections can be
prevented or cured with RSV in a dose dependent manner.
8.1. Anti-biofilm and anti-adhesion
Chronic infections are often caused by the bacteria that have the
ability to adhere to both biotic and abiotic and form biofilms. As biofilm
formation is associated with the virulence of bacterial infection due to
its resistance both to antibiotics and host defense mechanisms; inhibi-
tion of biofilm formation will lead to reduction of bacterial pathogen-
esis [97]. In Staphylococcus aureus and Staphylococcus epidermidis RSV
had antimicrobial effects at a subinhibitory concentration (SIC) of
50–1000 μg/ml and could inhibit 20–45% of biofilm formation in S.
aureus at (100 μg/ml) dose. Nevertheless, RSV exerted stimulatory ef-
fect on S. epidermidis biofilm formation [97]. Particularly, RSV has
antibacterial activities against clinical isolates of Methicillin-Resistant
Staphylococcus aureus at MIC range from 500 to 1000 μg/ml [86]. In
methicillin-resistant Staphylococcus aureus, RSV disturbs quorum sen-
sing (QS) and the synthesis of surface secretion proteins and capsular
polysaccharides by disturbing the expression of genes such as sdrD, spa,
hld, agrA, cap5B, and cap5C [98]. Evidences have shown that RSV in-
hibited biofilm formation in Staphylococcus aureus without affecting its
growth in a dose dependent manner also it could repress the hla gene
expression [76]. In Pseudomonas aeruginosa the most remarkable bio-
film inhibition was achieved by oxy RSV, trans-resveratrol, and RSV
dimer ε-viniferin. Moreover, the trans- RSV and ε-viniferin at 50 μg/ml
inhibited P. aeruginosa PAO1 and PA14 biofilm formation by 92% and
82%, respectively without antimicrobial activity [99]. Results of an-
other study regarding the activity of RSV on E. coli revealed that it can
inhibit the biofilm formation in EHEC; however, did not affect com-
mensal E. coli strains. Transcription of biofilm-related genes like Au-
toinducer-2 quorum sensing genes (lsrA, luxS, and luxR), curli genes
N. Bostanghadiri et al. Biomedicine & Pharmacotherapy 95 (2017) 1588–1595

Table 1
Mechanisms of resveratrol effects on viral infections.

Virus Mechanism of resveratrol action Effects on viral infection References

Influenza virus
Epstein-Barr virus
Herpes simplex virus
Respiratory syncytial virus
Human immunodeficiency virus
(HIV-1)
Varicella zoster virus
Duck enteritis virus (DEV)
Hepatitis C virus
Block nuclear-cytoplasmic translocation of virus Decrease in the expression of late viral proteins by [57]
inhibition of protein kinase C associated pathway
1) Inhibition of early antigen induction Prevents transformation and transcription of EBV [58]
2) Inhibition of early genes expression of lytic proteins
3) Inhibition of lytic gene expression and viral particle
production
4) Inhibition of protein synthesis and reduction of ROS
production
5) Downregulation of antiapoptotic proteins
1) Decreased production of early viral protein ICP4 1) Inhibition of viral transcription and DNA synthesis [59]
2) Rapid and transient release of reactive oxygen species 2) Prevented development of extravaginal lesions
3) Reduction of mRNA of ICP0, ICP4, ICP8, and HSV-1 DNA 3) Inhibition of HSV replication through ROS generation
polymerase
1) Control of toll-like receptor 3 expression, inhibition of 1) Reduction in inflammation and levels of interferon- [60]
TRIF signaling, and induction of M2 receptor gamma
2) Inhibition of viral induced toll-like receptor domain and 2) decreased production of interleukin-6, level of
TANK binding kinase 1 protein expression inflammatory cells and interferon-gamma
3) Enhanced interferon-gamma expression and airway
inflammatory response
4) Increased TNF, IFN and IL-2 production
Inhibition of DNA synthesis Inhibition of replication [61]
Reduction in synthesis of protein Decrease production [62]
Inhibition of synthesis of viral protein 1 and phosphorylation Inhibition of IL-6 and IFN [63]
of proinflammatory cytokines
Reversed antiviral effects of ribavirin and interferon Increased viral RNA replication [64]

(csgA and csgB), and motility genes (fimA, fimH, flhD, fliA, motB, qseBC)
were also significantly inhibited. With this in mind that bacterial mo-
tility has positive influence on the development of biofilm formation,
RSV might attenuate biofilm formation via disturbing its underlying QS
system and repressed several flagellar genes [100]. The outcomes of an
experiment conducted by He et al. revealed that in Fusobacterium nu-
cleatum, RSV attenuated the biofilm formation at concentrations ran-
ging from 1.5 to 25 μg/ml; however, increased aggregation of the
bacteria. In addition it showed pronounced effects on bacterial growth
rate at concentrations up to 50 μg/ml. Moreover, expression of ABC
transporter binding protein, LysR, Stress-induced proteins (such as
DnaK and GroEL), hemolysin, butyrate-acetoacetate CoA-transferase
was particularly down regulated in the presence of RSV [101]. In Pro-
pionibacterium acnes RSV inhibits the biofilm formation without anti-
microbial activity at 3.2 mg/ml dose [102] (Table 2).
8.2. Anti-quorum sensing and anti-pyocyanin activity
Quorum sensing (QS) is a way of bacterial communication that re-
lies on the density of bacterial population. Diffusible signaling mole-
cules play important roles in the following functions: bioluminescence,
virulence, biofilm formation and sporulation. Distinctly, there are dif-
ferent types of QS systems signal molecules that fall into the following
main groups: Autoinducer type 1 (AI-1), Autoinducer type 2 (AI-2),
Autoinducer type 3 (AI-3), and AI-1 which are found in many Gram-
negative bacteria; nevertheless, AI-2 is found in both Gram-positive and
Gram-negative bacteria. Collective evidences suggest that the ability to
form biofilms involves various gene expression and QS regulation.
Apparently, AI-2 synthesizes its master regulator luxR and luxS; lsrA
has been recognized as the transporter for AI-2. Furthermore, AI-2 sti-
mulates the formation of biofilm in E. coli via stimulating flagellar
motility. Eloquently, trans-resveratrol suppressed various important
genes for flagellar motility, interfere with AI-2 signaling and decreased
the formation of EHEC biofilm by down-regulating qseBC and flhDC
genes [100,101,103]. In a recent study regarding anti-quorum sensing
activity of RSV, piceatannol and oxyresveratrol were examined on
Pseudomonas aeruginosa. The results showed that they have potential for
anti-QS activities by suppressing the expression of the following genes:
lasR, lasI, rhlR and rhlI at concentration of 400 μΜ [104], also other
evidences demonstrated that RSV inhibits QS activity in Pseudomonas
aeruginosa [105] (Fig. 2).
P. aeruginosa have diverse virulence factors controlled by quorum
sensing, such as pyocyanin, rhamnolipid, and pyochelin. A study con-
ducted by Cho et al. demonstrated that RSV reduces pyocyanin pro-
duction [99]. Another study on P. aeruginosa PAO1 presented that RSV,
piceatannol and oxyresveratrol could motivate the decrease in pro-
duction of pyocyanin at sub-MIC concetrations [104] (Table 2).
8.3. Inhibition of bacterial motility
Swimming and swarming motilities significantly influence the for-
mation of biofilm by E. coli. Trans-resveratrol inhibits both swimming
and swarming of EHEC and represses some motility and flagellar genes,
such as flhD, fimA, fimH, and motB [100,106].
Another study performed on P. aeruginosa PAO1 showed that RSV,
piceatannol and oxyresveratrol had significant effect on swarming
motility even at 100 mM dose. Testing the effect of stilbenoids on
swarming motility of P. aeruginosa could specify further evidences re-
garding their potency to interfere with QS [104] (Table 2).
8.4. Combination and synergism effects of RSV
Bottari et al. proved synergism effects of RSV with
Sulfamethoxazole-trimethoprim (ST) for treatment of toxoplasmosis in
mice. They showed that acetylcholinesterase and creatine kinase ac-
tivities did not increase in infected T. gondii mice after treatment with
ST-RSV. Moreover, decreased adenylate kinase activity caused by T.
gondii infection was normalized by ST-RSV treatment [107]. Alayev
et al. studied the xenograft tumor model which represented that com-
bination of rapamycin and RSV lead to inhibition of autophagy, in the
tuberous sclerosis complex (TSC2-null). Furthermore, they showed this
combination could be effective for treatment of Lymphangioleiomyo-
matosis and other diseases with mechanistic target of mTORC1 sig-
naling pathway by inhibition of phosphatidylinositol-4,5-bisphosphate
3-kinase PI3K/Akt/mTORC1 signaling and activates apoptosis [108].
The results of another study on Chlamydia infections presented that

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Table 2
Summary of different mechanisms of Resveratrol anti-bacterial activity.

Mechanism of Organism Mechanism description Effective concentration Ref.

action

Anti-biofilm E. coli EHEC - Reduce expression of curli genes (csgA and csgB) 10 μg/ml [84]
- Interfere with AI-2 signaling
- Down regulating qseBC and flhDC genes
S. aureus - Repressed the α-hemolysin hla gene and the intercellular adhesion locus (icaA and 100 μg/ml [69]
icaD) - MIC: > 2000
- SIC: 500
10 μg/ml
MRSA - hld of the QS systems was up-regulated - MIC: 350 mg/ml [82]
- Inhibiting biofilm formation by disturbing QS, synthesis of surface protein, - MBC: > 800 mg/ml
capsular polysaccharide and enhance Agr function at the RNA level
S. epidermidis - Don’t have anti-biofilm activity and stimulated biofilm formation. MIC: > 2000- [69]
-SIC: 100
F. nucleatum - Gene expression was down regulated in the biofilm 1.5625–25 μg/ml [85]
P. acnes 0.02–0.32 (w/v)a [86]
P. aeruginosa - Suppressed the expression of QS-induced genes 50 μg/ml [88,83]
400 μΜ
L. monocytogenes 200 μg/ml [72]
Anti-QS P. aeruginosa - Suppressed the expression of QS-induced genes 400 μΜ [88,83]
Anti-hemolytic S. aureus - Repressed the α-hemolysin hla gene and the intercellular adhesion locus (icaA and (0.2–1.0%) 10 μg/ml [7,82]
icaD)
Anti-movement EHEC - Repressed several key motility and flagellar genes, such as flhD, fimA, fimH, and [84]
motB.
P. aeruginosa 100 μM [89]
P. mirabilis - Inhibited and blocked swarming through an RsbA-dependent pathway. 30–60 μg/ml [61]
Antibacterial H. pylori - Significant effects against oxidative stress and inflammation in H. pylori infected - 2.5 μg/ml [87,76,79,60]
mucosa through suppression of IL-8, iNOS, and NF-қB. - MIC: 16–32 μg/ml
- Reduced expression of F-type ATPases - MBC: 64 μg/ml
L. monocytogenes - Blocked HKLM-induced NADPH oxidase-1 mRNA and reactive oxygen species [72,71]
production.
- Blocked phosphorylation of both kinases induced by HKLM.
C. pneumoniae - Decreased IL-17 and IL-23 production in a time dependent manner 40 μM [58]
- Decreased IL-17 and IL-23 production in a time dependent manner in C.
pneumoniae-infected cells
A. butzleri - Decrease in both intracellular DNA content and metabolic activity. 100 μg/ml [73]
- An increase in the accumulation of EtBr, and the efflux pump inhibitor PAβN
reduced the MIC of resveratrol
A. cryaerophilus 50 μg/ml [73]
C. jejuni - Inhibition of adhesion to abiotic and biotic surfaces at 100 μg/mL MIC: 0.313 mg/ml [74]
H. ducreyi 500 μg/ml [59]
Xylella fastidiosa 200 μg/ml [63]
E. coli - Induces membrane damage in E. coli at early time point > 342 μg/ml [77,84,68,53,83,90]
- Direct damage or activation of phospholipases and damage of any secondary MIC:400 μg/ml
targets inside the cells

EHEC: Enterohemorrhagic Escherichia coli, P. aeruginosa: Pseudomonas aeruginosa, F. nucleatum: Fusobacterium nucleatum, S. aureus: Staphylococcus aureus, MRSA: methicillin-resistant
Staphylococcus aureus, S. epidermidis: Staphylococcus, epidermidis, P. acnes: Propionibacterium acnes, L. monocytogenes: Listeria monocytogenes, P. mirabilis: Proteus mirabilis, H. pylori:
Helicobacter pylori, C. pneumoniae: Chlamydia pneumoniae, A. butzleri: Arcobacter butzleri, A. cryaerophilus: Arcobacter cryaerophilus, C. jejuni: Campylobacter jejuni, H. ducreyi: Haemophilus
ducreyi, E. coli: Escherichia coli.
a
More than80% reduction for all strains when 0.32% (w/v) was used.

combined treatment with RSV and ofloxacin or clarithromycin have the above mentioned issues, additional data regarding the resveratrol’s
particularly strong inhibition on the IL-23 levels [81]. potential for prevention and treatment of infectious diseases are
needed, especially clinical trials. Indeed, it is recommended to do more
research for exploring new aspects of resveratrol usefulness. Future
9. Summary, conclusion, and recommendations
research should focus on: 1. Identifying a desirable synergistic combi-
nation for achieving a given result and to determine if resveratrol could
According to the previous studies, resveratrol has been considered
cause either additive or synergistic consequences in combination with
as a potential agent for management and prevention of infectious dis-
other therapies. Evidently, the present work focused on resveratrol as a
eases in humans. Most antibacterial agents destroy both normal flora
stand-alone therapeutic agent. However, it could be possible that re-
and the pathogenic invader organisms; However, RSV has eliminatory
sveratrol supplementation may synergistically enhance the effective-
effects on virulence determinants of an organism such as anti-biofilm,
ness of therapeutic compounds. 2. Eventually, the statistical analyses
anti-quorum sensing, anti-pyocyanin, anti- movement and anti-adhe-
regarding the effects of long-term resveratrol supplementation are quite
sion effects which is due to its antivirulence effect on pathogenic or-
essential. The acute effects of resveratrol are evident; nevertheless, its
ganisms. It was ultimately attained that in addition to the antibacterial
mechanism of action in the long term practices is not clear yet.
effect, RSV has antiviral, antifungal, and anti-parasite effects as well.
Therefore, it can be recommended as a natural product for anti-
microbial usage. In this study we comprehensively reviewed the anti-
Competing interest
microbial potency of RVS. The present study demonstrates RSV as a
natural antimicrobial agent in vitro; however, additional studies re-
The authors have declared that no competing interest exist.
garding its clinical usage could be quite helpful in the future. In spite of

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N. Bostanghadiri et al.
Fig. 2. A schematic representation of resveratrol inhibitory effects on quorum sensing, biofilm formation and motility of bacteria.
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