Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Nov. 15, 2024
Background
High
altitude
cerebral
edema
(HACE)
is
a
condition
where
the
central
nervous
system
experiences
severe
impairment
as
result
of
sudden
oxygen
deprivation
at
high
elevations.
At
present,
effective
measures
for
preventing
and
treating
this
are
still
lacking.
Eleutheroside
B
(EB),
primary
natural
active
compound
found
in
senticosus
,
has
demonstrated
various
biological
functions.
It
also
shown
significant
potential
addressing
acute
mountain
sickness
neurological
disorders.
However,
additional
investigation
required
to
explore
protective
effects
its
underlying
mechanisms
EB
on
HACE.
Methods
The
male
rats
received
pre-treatment
with
either
vehicle,
100
mg/kg
or
50
mg/kg,
Dexamethasone
4
coumermycin
A1
μg/kg.
To
simulate
hypobaric
hypoxia
environment
plateau
6,000
m,
chamber
was
utilized.
therapeutic
were
assessed
through
measurements
brain
water
content,
histopathological
observation,
evaluation
oxidative
stress
inflammatory
factors
using
immunofluorescence
ELISA.
Furthermore,
molecular
docking,
dynamics
simulation
Western
blot
employed
clarify
mechanism.
Through
these
analyses,
mechanism
by
which
HACE
identified.
Results
Pre-treatment
effect
against
effectively
reducing
down-regulating
HIF-1α
AQP4
protein
expression
induced
reversing
pathological
changes
tissue
neuron
damage.
Compared
group
treated
alone,
pre-treated
showed
reduction
levels
ROS
MDA,
well
an
increase
GSH.
In
addition,
led
decrease
IL-1β,
IL-6,
TNF-α.
Molecular
docking
simulations
indicated
that
strong
binding
affinity
JAK2/STAT3
signaling
pathway.
further
confirmed
significantly
downregulated
related
proteins
rats.
Additionally,
A1,
agonist
JAK2,
reversed
anti-oxidative
neuroinflammation
EB.
Conclusion
exerts
antioxidant
anti-neuroinflammatory
inhibiting
pathway
rat
model.
MedComm,
Journal Year:
2025,
Volume and Issue:
6(4)
Published: March 30, 2025
ABSTRACT
Signal
transducer
and
activator
of
transcription
3
(STAT3)
is
a
critical
factor
involved
in
multiple
physiological
pathological
processes.
While
STAT3
plays
an
essential
role
homeostasis,
its
persistent
activation
has
been
implicated
the
pathogenesis
various
diseases,
particularly
cancer,
bone‐related
autoimmune
disorders,
inflammatory
cardiovascular
neurodegenerative
conditions.
The
interleukin‐6/Janus
kinase
(JAK)/STAT3
signaling
axis
central
to
activation,
influencing
tumor
microenvironment
remodeling,
angiogenesis,
immune
evasion,
therapy
resistance.
Despite
extensive
research,
precise
mechanisms
underlying
dysregulated
disease
progression
remain
incompletely
understood,
no
United
States
Food
Drug
Administration
(USFDA)‐approved
direct
inhibitors
currently
exist.
This
review
provides
comprehensive
evaluation
STAT3's
health
disease,
emphasizing
involvement
cancer
stem
cell
maintenance,
metastasis,
inflammation,
drug
We
systematically
discuss
therapeutic
strategies,
including
JAK
(tofacitinib,
ruxolitinib),
Src
Homology
2
domain
(S3I‐201,
STATTIC),
antisense
oligonucleotides
(AZD9150),
nanomedicine‐based
delivery
systems,
which
enhance
specificity
bioavailability
while
reducing
toxicity.
By
integrating
molecular
mechanisms,
pathology,
emerging
interventions,
this
fills
knowledge
gap
STAT3‐targeted
therapy.
Our
insights
into
crosstalk,
epigenetic
regulation,
resistance
offer
foundation
for
developing
next‐generation
with
greater
clinical
efficacy
translational
potential.
Expert Opinion on Therapeutic Patents,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 16, 2025
Signal
transducer
and
activator
of
transcription
3
(STAT3),
a
member
the
STAT
protein
family,
serves
as
both
signal
factor.
Previous
studies
have
highlighted
its
pivotal
roles
in
regulating
cell
proliferation,
differentiation,
apoptosis,
well
immune
inflammatory
responses.
Consequently,
targeting
STAT3
has
emerged
promising
therapeutic
strategy
for
addressing
related
diseases.
This
review
offers
comprehensive
summary
progress
discovering
inhibitors,
with
focus
on
their
structural
diversity
structure-activity
relationships
presented
patent
literature
from
2022
to
present.
Over
past
decades,
significant
transformed
into
target
interest
drug
development.
Despite
these
advances,
no
STAT3-targeting
drugs
successfully
progressed
through
late-phase
clinical
trials,
largely
due
challenges
such
limited
selectivity
undesirable
side
effects.
These
obstacles
highlight
inherent
complexity
developing
safe
effective
inhibitors.
Nevertheless,
remains
highly
target,
ongoing
advancements
this
field
hold
potential
unlock
novel
strategies
STAT3-related
Pharmacological Research - Modern Chinese Medicine,
Journal Year:
2024,
Volume and Issue:
12, P. 100487 - 100487
Published: July 24, 2024
Alzheimer's
disease
(AD)
and
Parkinson's
(PD),
characterized
by
their
progressive
nature
debilitating
impact
on
individuals'
cognitive
motor
functions,
pose
a
significant
challenge
to
public
health.
Despite
extensive
research
efforts,
the
severity
of
dysfunction
remains
formidable,
with
gaps
persisting
in
understanding
its
underlying
mechanisms
developing
effective
therapeutic
interventions.
Natural
phytohormones
have
emerged
as
promising
candidates
for
managing
neurodegenerative
diseases,
offering
potential
avenues
intervention.
The
phytohormone
trans-zeatin
(tZ)
is
derivative
cytokinin
zeatin
(6-isopentenylaminopurine).
tZ
derivatives
such
N6-isopentyl
adenosine
(iPR),
t-zeatin
riboside
(tZR),
kinetin
(K),
(KR)
are
active
components
available
coconut
water
also
isolated
from
many
plant
extracts
that
aid
growth.
We
searched
various
online
databases
(Pub-Med,
WOS,
Google
Scholar)
last
twenty
years
using
keywords
disease,
phytohormones,
trans-zeatin,
cytokinins,
paired
traditional
Chinese
plants.
This
literature
review
sought
illuminate
role
cytokinins
AD
PD.
In
addition,
this
article
talked
about
biological
importance
understand
how
derivatives,
which
protect
neurons.
screened
75
articles.
Results
were
summarized,
compared,
identified
throughout
data
collection
interpretation.
TZ
garnered
attention
notable
activities
antioxidant,
anti-aging,
cytoprotective,
anti-inflammatory,
particularly
anti-Alzheimer
anti-Parkinson
effects.
may
be
useful
treatment
because
it
stops
cholinesterase
working,
amyloid
beta
(Aβ)
clumping
together,
changes
Nrf2/ARE
pathway.
prevents
degeneration
dopaminergic
neurons
lowering
JNK/P38
phosphorylation,
moderating
Bax-mediated
apoptosis,
blocking
caspase
3/7
activation.
Dietary
foods
could
incorporate
derived
(Cocos
nucifera)
other
natural
sources,
provide
variety
health
benefits.
Because
they
can
change
important
cellular
pathways
like
Nrf2,
NF-κB,
PI3K/Akt,
able
damage
slow
down
By
evaluating
trans-zeatin's
efficacy
preclinical
clinical
studies,
holds
promise
becoming
valuable
agent
combating
neurodegeneration
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Nov. 15, 2024
Background
High
altitude
cerebral
edema
(HACE)
is
a
condition
where
the
central
nervous
system
experiences
severe
impairment
as
result
of
sudden
oxygen
deprivation
at
high
elevations.
At
present,
effective
measures
for
preventing
and
treating
this
are
still
lacking.
Eleutheroside
B
(EB),
primary
natural
active
compound
found
in
senticosus
,
has
demonstrated
various
biological
functions.
It
also
shown
significant
potential
addressing
acute
mountain
sickness
neurological
disorders.
However,
additional
investigation
required
to
explore
protective
effects
its
underlying
mechanisms
EB
on
HACE.
Methods
The
male
rats
received
pre-treatment
with
either
vehicle,
100
mg/kg
or
50
mg/kg,
Dexamethasone
4
coumermycin
A1
μg/kg.
To
simulate
hypobaric
hypoxia
environment
plateau
6,000
m,
chamber
was
utilized.
therapeutic
were
assessed
through
measurements
brain
water
content,
histopathological
observation,
evaluation
oxidative
stress
inflammatory
factors
using
immunofluorescence
ELISA.
Furthermore,
molecular
docking,
dynamics
simulation
Western
blot
employed
clarify
mechanism.
Through
these
analyses,
mechanism
by
which
HACE
identified.
Results
Pre-treatment
effect
against
effectively
reducing
down-regulating
HIF-1α
AQP4
protein
expression
induced
reversing
pathological
changes
tissue
neuron
damage.
Compared
group
treated
alone,
pre-treated
showed
reduction
levels
ROS
MDA,
well
an
increase
GSH.
In
addition,
led
decrease
IL-1β,
IL-6,
TNF-α.
Molecular
docking
simulations
indicated
that
strong
binding
affinity
JAK2/STAT3
signaling
pathway.
further
confirmed
significantly
downregulated
related
proteins
rats.
Additionally,
A1,
agonist
JAK2,
reversed
anti-oxidative
neuroinflammation
EB.
Conclusion
exerts
antioxidant
anti-neuroinflammatory
inhibiting
pathway
rat
model.
