Peripheral Evolution of Tanshinone IIA and Cryptotanshinone for Discovery of a Potent and Specific NLRP3 Inflammasome Inhibitor
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 23, 2025
Natural
products
(NPs)
continue
to
serve
as
an
invaluable
source
in
drug
discovery,
and
peripheral
evolution
of
NPs
is
a
highly
efficient
strategy.
Herein,
we
describe
unified
"methyl
amide"
Tanshinone
IIA
Cryptotanshinone
for
discovery
NLRP3
inflammasome
inhibitors.
There
were
54
compounds
designed
prepared,
while
the
chemoinformatic
analysis
revealed
that
these
evolved
NP
analogues
occupy
unique
chemical
space.
Biological
evaluation
identified
5m
inhibitor,
could
directly
bind
NACHT
domain
protein
block
interaction
ASC,
thus
suppressing
ASC
oligomerization
assembly.
Molecular
dynamic
stimulations
amide
moiety
played
vital
role
binding
mode.
Moreover,
exhibited
therapeutical
efficacy
sepsis
NASH
mouse
model.
In
conclusion,
this
protocol
provides
new
vision
NPs'
novel
inhibitor.
Язык: Английский
The role of the NLRP3 inflammasome in the pathogenesis of asthma: inflammatory mechanisms and emerging therapeutic strategies
Kazan medical journal,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 24, 2025
This
article
focuses
on
the
pathophysiological
mechanisms
and
therapeutic
potential
in
management
of
bronchial
asthma,
a
global
health
challenge
with
increasing
prevalence.
The
pathogenesis
asthma
is
rooted
immune-mediated
inflammation
involving
formation
inflammasomes,
molecular
complexes
that
regulate
inflammatory
responses.
Inflammasomes,
particularly
NLRP3,
play
pivotal
role
disease
development
by
interacting
allergens
initiating
signaling
cascades
lead
to
production
pro-inflammatory
cytokines
such
as
interleukin-1β
(IL-1β)
Interleukin-18.
These
recruit
immune
cells,
including
mast
eosinophils,
T-lymphocytes,
which
contribute
airway
inflammation,
hyperreactivity,
obstruction.
examines
phenotypes,
infection-dependent
atopic
well
association
between
NLRP3
inflammasome
activation
impaired
lung
function,
steroid
resistance,
neutrophilic
inflammation.
Special
attention
given
cellular
involved
process,
interaction
T-helper
macrophages,
leading
release
histamine,
heparin,
lysosomal
enzymes,
reactive
oxygen
species,
nitric
oxide,
prostaglandins,
leukotrienes.
Inflammatory
mediators
IL-4,
IL-5,
IL-13
remodeling,
mucus
hypersecretion,
spasm.
Furthermore,
can
disrupt
epithelial
barrier
exacerbating
allergic
study
highlights
chronic
changes
tree
caused
prolonged
It
emphasizes
importance
regulation,
use
selective
inhibitor
MCC950,
effectively
reduces
demonstrates
promising
for
asthma.
concludes
underscoring
integrating
research
into
clinical
practice,
suggesting
targeted
therapy,
could
transform
treatment.
need
shift
toward
personalized
medicine
managing
diseases
like
Язык: Английский
Ticagrelor alleviates neuroinflammation after traumatic brain injury by inhibiting NLRP3 inflammasome-mediated pyroptosis
Neuroreport,
Год журнала:
2025,
Номер
36(6), С. 306 - 313
Опубликована: Март 26, 2025
Traumatic
brain
injury
(TBI)
is
often
accompanied
by
secondary
(SBI),
with
neuroinflammation
being
a
core
mechanism
of
SBI.
Pyroptosis
key
driver
neuroinflammatory
responses,
and
inhibiting
pyroptosis
can
reduce
after
TBI
promote
tissue
functional
recovery.
The
activation
the
NLRP3
inflammasome
mediates
classical
pathway,
ticagrelor
inhibit
activation.
This
study
aimed
to
investigate
differences
in
inhibition
induced
different
doses
targeting
inflammasome.
Mice
were
randomly
divided
into
four
groups:
sham,
TBI,
50
mg/kg
treatment,
150
treatment.
After
24
h
surrounding
was
collected
for
immunoblot
detection
pyroptosis-related
protein
expression
ELISA
inflammatory
cytokine
release.
On
day
3
BBB
permeability
edema
assessed
injection
Evans
blue
measurement
water
content.
7
mice
sacrificed,
extent
through
hematoxylin
eosin
Nissl
staining,
while
levels
markers
detected
immunohistochemistry.
21
Morris
maze
used
evaluate
neural
function
Compared
group,
high-dose
treatment
inhibited
mouse
tissue,
reduced
release
cytokines,
alleviated
edema,
lowered
levels,
promoted
recovery
(
P
<
0.05).
Therefore,
holds
promise
as
clinical
drug
treating
TBI.
Язык: Английский
Berberine Suppresses Influenza A Virus-Triggered Pyroptosis in Macrophages via Intervening in the mtROS-MAVS-NLRP3 Inflammasome Pathway
Viruses,
Год журнала:
2025,
Номер
17(4), С. 539 - 539
Опубликована: Апрель 7, 2025
Infection
with
influenza
A
virus
(IAV)
may
trigger
excessive
inflammatory
responses,
leading
to
severe
viral
pneumonia
and
accelerating
disease
progression.
Therefore,
controlling
these
responses
is
crucial
for
the
prevention
treatment
of
caused
by
IAV.
Berberine
(BBR),
an
isoquinoline
alkaloid
extracted
from
traditional
Chinese
medicine,
possesses
extensive
pharmacological
activities.
However,
its
immunoregulatory
effects
molecular
mechanisms
in
context
IAV
infection
require
further
investigation.
This
study
explored
impact
BBR
on
macrophage
pyroptosis
induced
infection.
Our
findings
revealed
that
effectively
inhibits
release
IL-1β
TNF-α
suppresses
gasdermin
D
(GSDMD)-mediated
a
dose-dependent
manner.
Further
research
indicates
alleviates
IAV-infected
cells
reducing
mitochondrial
reactive
oxygen
species
(mtROS),
inhibiting
antiviral
signaling
protein
(MAVS)
expression
blocking
activation
NOD-like
receptor
family
pyrin
domain
containing
3
(NLRP3)
inflammasome.
Experiments
using
siRNA
knockdown
MAVS
confirmed
pivotal
role
BBR’s
inhibition
IAV-induced
pyroptosis.
provides
scientific
basis
application
as
anti-inflammatory
drug
diseases
directs
future
endeavors.
Язык: Английский
The entrenchment of NLRP3 inflammasomes in autoimmune disease-related inflammation
Autoimmunity Reviews,
Год журнала:
2025,
Номер
unknown, С. 103815 - 103815
Опубликована: Апрель 1, 2025
Autoinflammation
and
autoimmunity
are
almost
"opposite"
phenomena
characterized
by
chronic
activation
of
the
immune
system,
'innate'
in
first
'adaptive'
second,
leading
to
inflammation
several
tissues
with
specific
protean
effectors
tissue
damage.
The
mechanism
involvement
multiprotein
complexes
called
'inflammasomes'
within
autoimmune
pictures,
differently
from
autoinflammatory
conditions,
is
yet
undeciphered.
In
this
review
we
provide
a
comprehensive
overview
on
NLRP3
inflammasome
contribution
into
pathogenesis
some
diseases.
response
autoantibodies
against
nucleic
acids
or
tissue-specific
antigens
activated
dendritic
cells
macrophages
patients
systemic
lupus
erythematosus.
Crucial
amplify
interleukin-1
overexpression
matrix
metalloproteinase
production
at
joint
level
rheumatoid
arthritis.
A
deregulated
occurs
serous
acini
salivary
lacrimal
glands
prone
Sjogren's
syndrome,
but
also
inflammatory
process
involving
endothelial
cells,
leucocyte
recruitment,
platelet
plugging
vasculitides.
Furthermore,
organ-specific
diseases
such
as
thyroiditis
hepatitis
may
display
hyperactive
inflammasomes
resident
thyroid
liver,
respectively.
Therefore,
it
not
unexpected
that
preclinical
studies
have
shown
how
inhibitors
significantly
overthrow
severity
different
slow
down
their
trend
towards
an
ominous
progression.
Specific
markers
could
reveal
subclinical
components
escaping
conventional
diagnostic
approaches
improve
monitoring
personalizing
treatment.
Язык: Английский