Antioxidants,
Год журнала:
2025,
Номер
14(3), С. 256 - 256
Опубликована: Фев. 23, 2025
Endothelial
dysfunction
(ED)
is
characterized
by
an
imbalance
between
vasodilatory
and
vasoconstrictive
factors,
leading
to
impaired
vascular
tone,
thrombosis,
inflammation.
These
processes
are
critical
in
the
development
of
cardiovascular
diseases
(CVDs)
such
as
atherosclerosis,
hypertension
ischemia/reperfusion
injury
(IRI).
Reduced
nitric
oxide
(NO)
production
increased
oxidative
stress
key
contributors
ED.
Aging
further
exacerbates
ED
through
mitochondrial
oxidative/nitrosative
stress,
heightening
CVD
risk.
Antioxidant
systems
like
superoxide-dismutase
(SOD),
glutathione-peroxidase
(GPx),
thioredoxin/thioredoxin-reductase
(Trx/TXNRD)
pathways
protect
against
stress.
However,
their
reduced
activity
promotes
ED,
vulnerability
IRI.
Metabolic
syndrome,
comprising
insulin
resistance,
obesity,
hypertension,
often
accompanied
Specifically,
hyperglycemia
worsens
endothelial
damage
promoting
Obesity
leads
chronic
inflammation
changes
perivascular
adipose
tissue,
while
associated
with
increase
The
NLRP3
inflammasome
plays
a
significant
role
being
triggered
factors
reactive
oxygen
nitrogen
species,
ischemia,
high
glucose,
which
contribute
inflammation,
injury,
exacerbation
Treatments,
N-acetyl-L-cysteine,
SGLT2
or
inhibitors,
show
promise
improving
function.
Yet
complexity
suggests
that
multi-targeted
therapies
addressing
metabolic
disturbances
essential
for
managing
CVDs
syndrome.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(21), С. 14447 - 14473
Опубликована: Окт. 25, 2023
NLRP3
inflammasome
is
a
multiprotein
complex
involved
in
host
immune
response─which
exerts
various
biological
effects
by
mediating
the
maturation
and
secretion
of
IL-1β
IL-18─and
pyroptosis.
However,
its
aberrant
activation
could
cause
amplification
inflammatory
effects,
thereby
triggering
range
ailments,
including
Alzheimer's
disease,
Parkinson's
rheumatoid
arthritis,
gout,
type
2
diabetes
mellitus,
cancer.
For
past
few
years,
as
an
attractive
anti-inflammatory
target,
NLRP3-targeting
small-molecule
inhibitors
have
been
widely
reported
both
academic
industrial
communities.
In
order
to
deeply
understand
advancement
inhibitors,
we
provide
comprehensive
insights
commentary
on
drugs
currently
under
clinical
investigation,
well
other
from
chemical
structure
point
view,
with
aim
new
for
further
development
inflammasome-mediated
diseases.
Antioxidants,
Год журнала:
2023,
Номер
12(7), С. 1396 - 1396
Опубликована: Июль 7, 2023
Myocardial
ischemia-reperfusion
injury
(MIRI)
is
caused
by
several
mechanisms,
including
the
production
of
reactive
oxygen
species
(ROS),
altered
cellular
osmolarity,
and
inflammatory
response.
Calcium
overload,
levels,
mitochondrial
ROS
are
also
involved
in
these
MIRI
processes,
resulting
irreversible
opening
permeability
transition
pore
(mPTP).
These
mechanisms
processes
associated
with
NLRP3
inflammasome
priming
activation,
which
can
induce
cell
death
pyroptosis
through
up-regulation
caspase-1
pathway
IL-18
release.
In
addition,
endothelial
dysfunction,
both
presence
absence
MIRI,
accompanied
decreased
nitric
oxide
production,
overproduction,
expression
adhesion
molecules
leukocyte
infiltration
plays
a
central
role,
thus
contributing,
to
alteration
coronary
flow,
typical
ischemic
heart
disease.
Given
intricate
interrelationship
between
NLRP3,
inhibitors
reduce
while
oxidative
stress
inflammation.
have
been
intensively
studied
as
anti-inflammatory
agents
basic
cardiovascular
sciences.
this
review,
we
analyze
interrelation
disease
effects
some
possible
therapeutic
condition.
All
compounds
considered
review
need
larger
studies
confirm
their
appropriate
use
clinical
scenarios
anti-ischemic
drugs.
Vascular Pharmacology,
Год журнала:
2024,
Номер
156, С. 107397 - 107397
Опубликована: Июнь 17, 2024
Several
factors
contribute
to
ischemia/reperfusion
injury
(IRI),
including
activation
of
the
NLRP3
inflammasome
and
its
byproducts,
such
as
interleukin-1β
(IL-1β)
caspase-1.
However,
may
paradoxically
exhibit
cardioprotective
properties.
This
study
aimed
assess
protective
effects
novel
inhibitor,
INF195,
both
in
vitro
ex
vivo.
To
investigate
relationship
between
myocardial
IRI,
we
synthetized
a
series
inhibitors,
investigated
their
putative
binding
mode
via
docking
studies.
Through
studies
identified
INF195
optimal
for
inhibition.
We
measured
infarct-size
isolated
mouse
hearts
subjected
30-min
global
ischemia/one-hour
reperfusion
presence
three
different
doses
(5,
10,
or
20-μM).
analyzed
caspase-1
IL-1β
concentration
cardiac
tissue
homogenates
by
ELISA.
Statistical
significance
was
determined
using
one-way
ANOVA
followed
Tukey's
test.
reduces
NLRP3-induced
pyroptosis
human
macrophages.
Heart
pre-treatment
with
5
10-μM
significantly
infarct
size
levels.
Data
suggest
that
intracardiac
contributes
IRI
low
exert
reducing
size.
at
20-μM,
efficacy
declines,
leading
lack
cardioprotection.
Research
is
required
determine
if
high
have
off-target
dual
roles,
potentially
eliminating
harmful
functions
NLRP3.
Our
findings
highlight
potential
new
chemical
scaffold,
amenable
further
optimization,
provide
inhibition
cardioprotection
setting.
Bioactive Materials,
Год журнала:
2024,
Номер
35, С. 461 - 476
Опубликована: Фев. 19, 2024
Obesity
triggers
inflammatory
responses
in
the
microenvironment
of
white
adipose
tissue,
resulting
chronic
systemic
inflammation
and
subsequent
development
non-communicable
diseases,
including
type
2
diabetes,
coronary
heart
disease,
breast
cancer.
Current
therapy
approaches
for
obesity-induced
diseases
persist
prioritizing
symptom
remission
while
frequently
overlooking
criticality
targeting
alleviating
at
its
source.
Accordingly,
this
review
highlights
importance
obese
tissue
promising
potential
employing
immunotherapy
to
target
it
as
an
effective
therapeutic
approach
induced
by
obesity.
Additionally,
discusses
challenges
offers
perspective
about
tissue.
