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REVIEW ARTICLE
Molecular Basis of the Beneficial Actions of Resveratrol
Gast
on Repossi,
a
Undurti N. Das,
b
and Aldo Renato Eynard
a
a
Instituto de Investigaciones en Ciencias de la Salud, C
atedra de Biolog
ıa Celular, Histolog
ıa y Embriolog
ıa, Facultad de Ciencias M
edicas, Universidad
Nacional de C
ordoba, Ciudad Universitaria, C
ordoba, Argentina
b
UND Life Sciences, Battle Ground, Washington, USA
Received for publication December 31, 2019; accepted January 24, 2020 (ARCMED_2019_1186).
Resveratrol modulates the transcription factor NF-kB, cytochrome P450 isoenzyme CY-
P1A1, expression and activity of cyclooxygenase (COX) enzymes, Fas/Fas ligand medi-
ated apoptosis, p53, mTOR and cyclins and various phospho-diesterases resulting in an
increase in cytosolic cAMP levels. Cyclic AMP, in turn, activates Epac1/CaMKKb/
AMPK/SIRT1/PGC-1apathway that facilitates increased oxidation of fatty acids, mito-
chondrial respiration and their biogenesis and gluconeogenesis. Resveratrol triggers
apoptosis of activated T cells and suppresses tumor necrosis factor-a(TNF-a),
interleukin-17 (IL-17) and other pro-inflammatory molecules and inhibits expression of
hypoxia inducible factor-1a(HIF-1a) and vascular endothelial growth factor (VEGF) that
may explain its anti-inflammatory actions. Polyunsaturated fatty acids (PUFAs) and their
anti-inflammatory metabolites lipoxin A4, resolvins, protectins and maresins have a sig-
nificant role in obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome and cancer.
We observed that PUFAs (especially arachidonic acid, AA) and BDNF (brain-derived
neurotrophic factor) protect against the cytotoxic actions of alloxan, streptozotocin, ben-
zo(a)pyrene (BP) and doxorubicin. Thus, there is an overlap in the beneficial actions of
resveratrol, PUFAs and BDNF suggesting that these molecules may interact and augment
synthesis and action of each other. This is supported by the observation that resveratrol
and PUFAs modulate gut microbiota and influence stem cell proliferation and differenti-
ation. Since resveratrol is not easily absorbed from the gut it is likely that it may act on
endocannabinoid and light, odor, and taste receptors located in the gut, which, in turn,
convey their messages to the various organs via vagus nerve. Ó2020 IMSS.
Published by Elsevier Inc.
Key Words: Resveratrol, Polyunsaturated fatty acids, Brain-derived neurotrophic factor, Cytotoxic,
Lipoxin A4, Metabolic syndrome, Cancer.
Introduction
Resveratrol (3,5,40-trihydroxy-trans-stilbene) (RSV) is a
stilbenoid produced by several plants in response to injury
or pathogens such as bacteria or fungi. Food sources of
RSV include the skin of grapes, blueberries, raspberries,
and mulberries. Highest concentrations of RSV are present
in grape, and, more precisely, in grape skin. Thus, red wine
is the most concentrated food source of RSV (1e3). Re-
sveratrol exists as two geometric isomers: cis- (Z) and
trans- (E). The trans- and cis resveratrol can be either free
or bound to glucose. The trans- form seems to have the ma-
jor biological effects.
The anti-inflammatory actions of flavonoid RSV is
mediated by its modulatory actions on transcription factor
NF-kB, cytochrome P450 isoenzyme CYP1A1, cyclooxy-
genase (COX) enzymes, Fas/Fas ligand mediated apoptosis,
p53, mTOR, cyclins, various phospho-diesterases and
Epac1/CaMKKb/AMPK/SIRT1/PGC-1apathway. These
actions facilitate increased oxidation of fatty acids,
mitochondrial biogenesis and respiration, and gluconeogen-
esis. RSV induces apoptosis of activated T cells and
suppresses the production of pro-inflammatory tumor ne-
crosis factor-a(TNF-a), interleukin-17 (IL-17) and other
pro-inflammatory molecules. RSV inhibits expressions of
hypoxia inducible factor-1a(HIF-1a) and vascular endo-
thelial growth factor (VEGF) leading to a decrease in
Address reprint requests to: Undurti N. Das, UND Life Sciences, 2221
NW 5
th
St. Battle Ground, Washington, WA 98604, USA; Phone: (þ54)
0351 4334020; FAX: þ54 0351 4334021; E-mail: Undurti@hotmail.com
0188-4409/$ - see front matter. Copyright Ó2020 IMSS. Published by Elsevier Inc.
https://doi.org/10.1016/j.arcmed.2020.01.010
Archives of Medical Research -(2020) -
neo-angiogenesis implying that it could be of benefit in dia-
betic retinopathy (DR) (4,5) and cancer (6). RSV activates
Sirtuin 1 (SIRT1) (7), a molecule belonging to histone deace-
tylases, and peroxisome proliferator-activated receptor-gco-
activator-1a(PGC-1a) and thus, improves the function of
mitochondria (8,9). Since SIRT1 may function as an anti-
ageing molecule and delays age-associated diseases, it sug-
gests that RSV may have similar function. Overexpression
of SIRT1 and RSV enhances insulin sensitivity (10e13)
and could be of benefit in DR (14e17)(Figures 1 and 2).
RSV binds to tyrosyl transfer-RNA (tRNA) synthetase
(TyrRS) to enhance a poly (ADP-ribose) polymerase 1
(PARP1)/NADþdriven signaling cascade to activate p53
(18). Cells treated with RSV showed a 14 fold increase in
the action of superoxide dismutase (SOD) (19) that led to
reduced levels of superoxide anion resulting in restoration
of mitochondrial dysfunction to normal. RSV by activating
SIRT1 favors migration of FOXO transcription factors to
the nucleus (20), which stimulates FOXO3a transcriptional
activity (21). SOD is a target of FOXO3a, and MnSOD
expression is strongly induced in cells overexpressing FOX-
O3a (20). High expression of SOD with mild changes in
catalase (CAT) and glutathione peroxidase (GPX) expres-
sion in cancer cells results in the mitochondrial
accumulation of H2O2 leading to cancer cell apoptosis
(21). This is somewhat similar to the actions of exercise,
which also causes strong up-regulation of SOD, CAT and
GPX. These results are interesting since regular exercise
decreases the incidence of cancer (6,22,23).
Resveratrol Suppresses Inflammation and has
Cytoprotective Properties
RSV has anti-inflammatory actions. For example, RSV trig-
gers apoptosis of activated T cells and downregulates TNF-
a, interferon-g(IFN-g), interleukin (IL)-2, IL-9, IL-12, IL-
17, macrophage inflammatory protein-1a(MIP-1 a), and
monocyte chemoattractant protein-1 (MCP-1) secretion
(24e30). RSV inhibits both HIF-1aand VEGF that are
overexpressed in DR and in cancer that may explain some
of its beneficial actions (31e33). The anti-inflammatory ac-
tions of RSV are in support of its beneficial actions in in-
flammatory and autoimmune diseases (34e38)(
Figure 2).
In addition, RSV has cytoprotective actions. Bisphenol,
an endocrine disruptor present in plastics and the end prod-
uct component of the degradation of industrial plastic-
related wastes, is known to promote development and pro-
gression of estrogen-dependent cancer and increase cell
Figure 1. Scheme showing various actions of resveratrol that may form the basis of its beneficial actions. (modified from https://https://doi.org/10.1016/j.nut.
2015.08.017).
2Repossi et al./ Archives of Medical Research -(2020) -
growth. The increased cell viability and growth induced by
bisphenol A could be reversed by RSV (39). Bisphenol A
decreased expression of p21, which promotes cell cycle ar-
rest and plays an important role in halting cell proliferation
and increased the expression of cell cycle-dependent kinase
2 (CDK2), which was reverted to normal by RSV. Further-
more, increase in cyclin D1 secondary to downregulation of
p21 can also be restored to normal by RSV treatment, ex-
plaining its antiproliferative action on estrogen-dependent
ovarian cancer (39).
Bisphenol A plays a significant role in visceral obesity-
related low-grade chronic systemic inflammation (LGCI)
(40) and autism (41). Prenatal exposure to bisphenol A in-
duces DNA methylation changes in the transcriptionally
relevant region of the BDNF gene in the hippocampus. Bi-
sphenol activates stem cell Pax-6, an ectoderm marker, thus
interferes with the development of eyes, other sensory or-
gans, and certain neural and epidermal tissues usually
derived from ectodermal tissues (42). Bisphenol A admin-
istered to zebra fish (43) and Xaenopus laevis (44) resulted
in severe eye and retina malformations. Brain-derived neu-
rotrophic factor (BDNF) methylation changes have been re-
ported in the cord blood of humans exposed to high
maternal bisphenol A levels in utero (45). BDNF expres-
sion and DNA methylation are altered in depression,
schizophrenia, bipolar disorder, DR (46,47) and autism.
Decreased plasma levels of BDNF has been reported in
obesity, type 2 diabetes mellitus, DR (48) and metabolic
syndrome (49,50) indicating that environmental agents such
as bisphenol and benzo(a)pyrene alter the expression and
actions of BDNF that may lead to the development of
several diseases. Our recent studies revealed that BDNF
could function as a cytoprotective molecule preventing
the cytotoxic actions of alloxan, streptozotocin, benzo(a)
pyrene (BP), a common environmental pollutant, and
anti-cancer drug doxorubicin (51). This cytoprotective ac-
tion of BDNF is somewhat similar to the observed cytopro-
tective action of RSV against bisphenol A-induced autism,
type 2 diabetes mellitus and metabolic syndrome (52e54).
This suggest that in all probability RSV may augment
BDNF synthesis (6,55).
Recently, we observed that both plasma and vitreal fluid
BDNF levels are low in subjects with type 2 diabetes mel-
litus and those with DR (48). This is supported by in vitro
and bioinformatics studies that showed that BDNF interacts
with various polyunsaturated fatty acids (PUFAs) and their
anti-inflammatory metabolites such as lipoxin A4 (LXA4),
resolvins and protectins (49,50,56). Subsequent studies re-
vealed that BDNF enhances the production of LXA4, while
LXA4 augmented the synthesis and release of BDNF (Un-
published data). Thus, a close interaction exists between
BDNF and various PUFAs and together they may bring
about that their cytoprotective, anti-inflammatory and
anti-diabetic actions ((48e51,55e60)). BDNF and LXA4
Figure 2. Scheme showing the actions of resveratrol. Macrophages (MF), Programmed Cell Death-1 protein (PD-1).
3Molecular Basis of the Actions of Resveratrol
and other lipids AA, EPA, DHA, resolvins, protectins and
maresins play a significant role in type 2 diabetes mellitus,
DR, obesity and metabolic syndrome, autism, depression
and schizophrenia, (6,49e51,55e60) and augment each
other’s action(s) implying a close interaction(s) between
several proteins and lipids.
It is noteworthy that RSV (61) and LXA4, AA, EPA and
DHA have anti-cancer actions (62e68). RSV and LXA4
inhibit the production of pro-inflammatory molecule
PGE2 and inducible nitric oxide (iNO) synthesis
(62,69e71). The similarity in the anti-cancer and anti-
inflammatory actions of RSV and LXA4 implies that
RSV may augment the production of LXA4 that may be
relevant to their beneficial actions in type 2 DM, DR,
obesity, metabolic syndrome, autism, depression and
schizophrenia (52,72e75). In addition, resveratrol, PUFAs
and LXA4 modulate gut microbiota and proliferation and
differentiation of stem cells (66,75e79)(Figures 1 and 2).
Beneficial Activities of Resveratrol in DR
It is well documented that inflammatory process has a role
in the etiopathogenesis of DR and AMD (adult macular
degeneration) (80,81). Persistence of hyperglycemia and
other metabolic perturbations results in low-grade systemic
inflammatory process that results in deterioration of retinal
pigmentary epithelial (RPE) cells leading to the impairment
of the blood-retinal barrier (BRB) and consequently the loss
of central vision (82).
Experimental and clinical studies indicated that in DM
there could occur significant damage to the RPE- photore-
ceptors (PRs). RPE cells avidly phagocyte and digest oldest
and damaged PR outer segments, a phenomenon abnor-
mally increased in DM that requires large amounts of en-
ergy and oxygen. Outer segments of PRs are packed with
membranous sacs notably enriched in LC-PUFAs; whose
composition are altered in DM resulting in increased perox-
idation. As a consequence, all retinal cell populations and
vascular endothelial cells are exposed to significantly high
levels of oxidative stress. This can lead to apoptosis of RPE
cells and photoreceptors (Repossi et al, unpublished re-
sults). RSV can enhance the survival and improve phago-
cytic capacity of RPE cells that have been exposed to
oxidants (83). Human RPE cells challenged with H
2
O
2
can be protected by RSV by inducing a significant and
dose-dependent increase in antioxidant defense system by
enhancing the activity of reduced glutathione and suppress-
ing the production of reactive oxygen species (ROS) by
RPE cells. These evidences suggest that RSV exerts potent
antioxidant action (84).
RSV has significant antiangiogenic action. In general,
neovascularization is a normal physiological event that is
needed for repair and wound healing. But this could be a
pathological event in DR and AMD. Using retinal pigment
epithelial ARPE-19 cell line, Latruffe and co-workers
showed that RSV exerts anti-angiogenic action (85) that
seems to be mediated by its ability to inhibit VEGF-A
secretion and COX activity (1,3). In a mouse model of path-
ological neovascular lesions, RSV treatment normalized
VEGF mRNA level (86).
Low-grade systemic inflammation is associated with
abnormal oxidation that has been implicated in the pathobi-
ology of several diseases including DM, metabolic syn-
drome, obesity, psoriasis, Crohn’s Disease, cardiovascular
diseases, arthritis and cancer. Low serum BDNF and higher
levels of ILe6 and IL-10 observed in vitreous of DM pa-
tients are considered risk factors for DR development
(48). Interestingly, many polyphenols (resveratrol,
epigallocatechin-gallate, curcumin, genistein, phtalates)
inhibit COX-2 expression in a dose-dependent manner
(2). RSV binds to the active site of COX enzyme and thus,
block COX binding to AA and prevent its further catalysis
(87). In addition, RSV down-regulates COX-2 expression
by acting on NF-kB and the AP-1 complex transcription
factors, which are under the control of the signaling ki-
nases: IkkBaprocessing to IkBap50/p65 and MAPK/
ERK/p38/JNK. RSV has been shown to prevent the phos-
phorylation of IkkBaand MAPK (29).
RSV and Endocannabinoids
The fact that RSV is not easily absorbed but yet has shown
several beneficial actions when given orally suggests that it
may act locally in the gut that, in turn, produces systemic
actions. One such possibility is that RSV may act on widely
distributed gut associated endocannabinoid system—a fam-
ily of endogenous ligands, receptors, and enzymes- that are
present in the heart, liver, pancreas, skin, reproductive tract
and nervous system. Endocannabinoids are associated with
many disorders, including diabetes, hypertension, infer-
tility, liver disease, appetite, inflammatory bowel disease
and vomiting (88,89). The main endocannabinoid receptor,
CB
1
is the most abundant G proteinecoupled receptors in
the neurons of the brain and is also present in the heart,
liver, pancreas, skin, reproductive tract and other tissues.
Chronic consumption of a high-fat and high-sugar diet ele-
vates the levels of endocannabinoids in the gut and blood
(90). Blocking endocannabinoids decreased overeating in
the animals. Endocannabinoids interact with other neuro-
transmitters: in the reproductive tract with steroid hor-
mones; in the muscles, with myokines; and so on.
Endocannabinoids act as appetite-promoting signal, control
food intake by way of signals generated in the gut and thus,
may have a role in obesity and metabolic syndrome. In
obesity, both CB
1
and CB
2
receptors are upregulated
throughout the body, including liver and adipose tissue
(91). Activation of CB
1
receptors increases food intake
and affects energy metabolism in peripheral tissues. In type
2 diabetes, endocannabinoids and their receptors are
4Repossi et al./ Archives of Medical Research -(2020) -
upregulated in circulating macrophages and contribute to
the loss of pancreatic beta cells.
Endocannabinoids are Effective Pain Relievers and Have
Anti-inflammatory Actions
RSV and light, odor and taste receptors. Yet another possi-
bility by which RSV may be able to produce its beneficial
actions is by acting on the light, odor, and taste receptors
present in the gut and other tissues (Figures 3 and 4). Light,
odor and taste receptors (or receptors of similar nature)
located in our eyes, noses, and tongues exist in many loca-
tions in the body, including skin, heart, lungs, kidneys, mus-
cles, and sperm. They are involved in regulation of blood
pressure and enhance muscle and skin regeneration. In
the kidney, for example, short-chain fatty acids produced
by gut bacteria (RSV can act on gut microbiota) can
activate olfactory receptor 78 (Olfr78) and trigger changes
in blood pressure. Short-chain fatty acids decrease blood
pressure, suggesting that Olfr78 by itself normally in-
creases blood pressure in response to the compounds. Non-
olfactory receptor called Gpr41 that decreased blood
pressure in response to short-chain fatty acids shows a
stronger effect than Olfr78. It is likely that these two recep-
tors interact with each other to regulate blood pressure (92).
Olfactory receptors are expressed highly in a number of
different types of cancer cells and stimulating those recep-
tors can shrink tumors in vitro (93).
Melanopsin gene Opn4 is present throughout the blood
vessels, and Opn4 knockout mice and its pharmacological
inhibitors showed that melanopsin mediates the relaxation
of blood vessels in response to light. It is known that photo-
relaxation is regulated by G proteinecoupled receptor ki-
nase 2 (GRK2). While exposure to light alone could
Figure 3. Mechanism(s) of development of tolerogenic microenvironment in the gut. Helminths and bacteria secretory products (HES) induce T regulatory
cells (Tregs) generation in the gut and Foxp3 expression, which is dependent on signaling through T cell TGF-bR. Short chain fatty acids (SCFAs), such as
butyric acid, secreted by gut microbiota induce IL-10eproducing Tregs in the colonic lamina propria and is dependent on the production of B. fragilis poly-
saccharide A (PSA) and the expression of T cell TLR2. T regulatory cells induction is at least, in part, due to the stimulation of TGF-bsecretion by intestinal
epithelial cells that may result in a tolerogenic intestinal environment in the gut. It is likely that RSV may act on gut microbiota and colonic cells to develop
tolerogenic gut environment so that many gut-associated diseases are suppressed.
5Molecular Basis of the Actions of Resveratrol
cause a 20e25%relaxation of blood vessels, coupling light
with a GRK2 inhibitor resulted in a 75e100% relaxation.
Human aortic smooth muscle cells produce melanopsin
(Opsin4), a photopigment (that is normally seen in the hu-
man and mouse retina) that mediates relaxation of the
vasculature in response to blue light. Melanopsin has been
implicated in a number of light-induced phenomena
including regulation of the circadian clock, constriction of
the pupil in response to light, and effects on alertness,
learning, and metabolism (94,95).
Sweet and bitter taste receptors expressed in tuft cells in
the small intestine’s epithelium detect parasites and stimu-
late the immune system response. Taste receptors in the gut
detect nutrients from food. These taste receptors are also
present in mouse testes and sperm and knocking them out
render mice infertile. Recent studies indicate a role for taste
receptors in body’s immune reaction to certain bacteria and
parasites. Solitary chemosensory cells expressing bitter
taste receptors are present in the mouse upper respiratory
tract and molecules produced by gram-negative bacteria
to communicate with each other activated these receptors
and stimulated the secretion of inflammatory peptides to
initiate an innate immune response (96,97). Upper respira-
tory cells that have motile cilia express bitter taste receptors
that can sense and respond to bacterial signaling molecules.
These ciliated cells’ taste receptors can stimulate the innate
immune system upon binding to bacterial compounds and
are also likely have a role in immune responses in the
Figure 4. Mechanism(s) of tuft cell-induced immune events in the gut. Tuft cells release IL-25 on exposure to gut bacteria and worms which stimulates ILC2s
to produce IL-13 that stimulates stem cells to differentiate into Tuft cells. Tuft cells sense pathogens involving the mTORC1 complex and Raptor. Increased
IL-25 release by Tuft cells drives IL-13edependent expansion of the Tuft cell lineage. Tuft cells contain light, odor and taste receptors that ender them to
sense RSV and other polyphenols. SCFAs act on Tuft cells and their light, odor and taste (or similar) receptors to bring about the beneficial actions of gut
microbiota. RSV acts on gut microbiota to enhance their production and secretion of SCFAs and both RSVand SCFAs stimulate light, odor and taste receptors
present on the Tuft cells to bring about their beneficial actions that are carried to various other organs through the vagus nerve.
6Repossi et al./ Archives of Medical Research -(2020) -
gut. Taste receptors are expressed by gut tuft cells, and so
are likely to be involved in reacting to food and may play
a role in detecting microbes (98e100).
Since RSV is not easily absorbed yet has many actions,
one potential possibility is that its actions in the gut are
somehow transmitted to the various other tissues of the
body. Assuming that very small amounts of RSV and its
metabolites are absorbed from the gut, it can be suggested
that they act on endocannabinoid and light, odor, and taste
receptors located in the gut and elsewhere and bring about
their actions. This proposal needs to be verified in future
studies. It is also suggested that endocannabinoid, light,
odor and taste receptors convey their messages to the
various organs in the body and especially, to brain via vagus
nerve.
Helminths and bacteria induce Tregs (T regulatory cells)
generation in the gut and Foxp3 expression by their secre-
tory products (HES), which is dependent on signaling
through T cell TGF-bR. SCFAs (short chain fatty acids
such as butyric acid) secreted by gut microbiota induce
IL-10eproducing Tregs in the colonic lamina propria and
is dependent on the production of B. fragilis polysaccharide
A (PSA) and the expression of T cell TLR2. Treg induction
is at least, in part, due to the stimulation of TGF-bsecretion
by intestinal epithelial cells that may result in a tolerogenic
intestinal environment in the gut. It is likely that RSV may
act on gut microbiota and colonic cells to develop tolero-
genic gut environment so that many gut-associated diseases
are suppressed.
Tuft cells release IL-25 on exposure to gut bacteria and
worms which stimulates ILC2s to produce IL-13 that stim-
ulates stem cells to differentiate into Tuft cells. Tuft cells
sense pathogens involving the mTORC1 complex and
Raptor. Increased IL-25 release by Tuft cells drives IL-
13edependent expansion of the Tuft cell lineage. Tuft cells
contain light, odor and taste receptors that ender them to
sense RSV and other polyphenols. SCFAs act on Tuft cells
and their light, odor and taste (or similar) receptors to bring
about the beneficial actions of gut microbiota. RSV acts on
gut microbiota to enhance their production and secretion of
SCFAs and both RSV and SCFAs stimulate light, odor and
taste receptors present on the Tuft cells to bring about their
beneficial actions that are carried to various other organs
through the vagus.
Conclusions
It is evident from the preceding discussion that RSV has
many actions that may account for its beneficial actions
in several diseases (Figures 1 and 2). RSV could be a prom-
ising therapeutic agent to prevent pathological neo-
angiogenesis seen in DR and AMD. Despite its many useful
actions, the low bioavailability of RSV is a hindrance to its
meaningful therapeutic application. Poor bioavailability of
RSV is due to its extensive hepatic gluconuridation and sul-
fation. The low bioavailability of RSV also implies that its
actions are predominantly in the gut rather than due to its
availability in significant amounts in the circulation. In this
context, action of RSV on gut microbiota and its ability to
act on duodenal-mucosal SIRT1 and thus, enhance insulin
sensitivity and lower hepatic glucose production needs spe-
cial consideration. Studies revealed that in addition to its
action on duodenal mucosa, RSV initiates a gut-brain-
liver axis that improves hypothalamic insulin sensitivity
(52). These results are supported by the observation that
acute central (medio-basal hypothalamus, MBH) or sys-
temic injections of RSV induced marked improvement in
insulin sensitivity by acting on hypothalamic SIRT1.
Blockade of the K(ATP) channel and hepatic vagotomy
significantly attenuated the effect of central RSV on hepatic
glucose production, suggesting that RSV improves glucose
homeostasis mainly through a central SIRT1-dependent
pathway and that the MBH is a major site of RSV action
(101).
Despite these impressive actions (seen mainly in vitro
and experimental animals), RSV could not be brought to
the clinic due to its poor systemic bioavailability and
non-availability of relevant pre-clinical toxicological
studies. There are very few studies that evaluated the ac-
tions of RSV when systemically administered (102). Such
studies are needed to know the possible clinical implica-
tions of RSV and to exploit them in the clinic. To achieve
these objectives, newer methods of delivery need to be
developed that could include microencapsulation or nano-
particles of resveratrol such that they could be absorbed
better from the gut to improve its bioavailability (103).
Further research needs to be performed to know the half-
life, tissue distribution, tissue affinity, and local metabolism
and actions of RSV in various tissues of the body. In order
to target specific tissues or cells, it (RSV) may be conju-
gated with specific monoclonal antibodies and administer
it in situ. It may be possible to develop analogues of RSV
that have increased affinity to CB1, light, odor, and taste re-
ceptors present in the gut. These receptors may have the
ability to sense not only RSV and similar compounds pre-
sent in our diet, but sense gut microbiota and their metab-
olites. This could be one of the mechanisms by which the
actions of gut microbiota and their metabolites on various
organs and diseases is elicited.
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