Molecular Medicine Reports,
Год журнала:
2023,
Номер
28(5)
Опубликована: Сен. 8, 2023
Diabetic
nephropathy
is
one
of
the
most
significant
complications
diabetes,
resulting
in
increased
patient
mortality.
Dapagliflozin
an
inhibitor
sodium‑glucose
cotransporter
2
that
has
important
protective
effect
on
kidney.
Recent
studies
showed
pyroptosis
involved
advancement
diabetic
(DN).
However,
potential
molecular
mechanisms
underlying
association
between
and
renal
podocyte
injury
DN
remain
unclear.
Thus,
present
study
investigated
anti‑pyroptotic
function
dapagliflozin
podocytes
further
clarified
mechanisms.
In
this
study,
a
model
lipid
metabolism
disturbance
was
established
through
palmitic
acid
(PA)
induction
mouse
clone
5
(MPC5)
cell
line.
MPC5
PA‑induced
measured
by
ELISA,
western
blotting,
quantitative
PCR
Hoechst
33342/propidium
iodide
double‑fluorescence
staining.
The
role
HO‑1
using
knockdown
overexpression
experiments.
It
found
attenuated
expression
pyroptosis‑related
proteins,
including
nucleotide
oligomerization
domain‑like
receptor
thermal
protein
domain
associated
3,
apoptosis‑associated
speck‑like
containing
caspase
activation
recruitment
domain,
caspase‑1,
IL‑18
IL‑1β
PA
group.
Meanwhile,
heme
oxygenase
1
(HO‑1)
level
decreased
within
PA,
reversed
dapagliflozin.
Furthermore,
proteins
inflammatory
cytokines
reduced
following
overexpression.
Therefore,
these
results
suggested
ameliorates
mediating
HO‑1,
which
nephropathy.
Brain Research Bulletin,
Год журнала:
2025,
Номер
224, С. 111296 - 111296
Опубликована: Март 10, 2025
Alzheimer's
disease
(AD)
is
the
chief
cause
of
dementia
and
related
mortality
worldwide
due
to
progressive
accumulation
amyloid
peptide
(Aβ)
hyperphosphorylated
tau
protein.
These
neuropathological
changes
lead
cognitive
impairment
memory
dysfunction.
Notably,
most
Food
drug
Administration
(FDA)
approved
anti-AD
medications
such
as
tacrine
donepezil
are
engaged
with
symptomatic
relief
but
do
not
reverse
underlying
AD
neuropathology.
Therefore,
searching
for
new
advisable.
It
has
been
shown
that
inflammatory
signaling
pathways
mitogen-activated
protein
kinases
(MAPK)
intricate
Aβ
neuropathology
in
AD.
In
addition,
inhibition
brain
MAPK
plays
a
critical
role
mitigating
dysfunction
early-onset
Though,
fundamental
mechanisms
beneficial
effects
inhibitors
were
fully
explained.
this
review
aims
discuss
potential
molecular
Journal of Alzheimer s Disease,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 20, 2025
Background
Alzheimer's
disease
(AD)
is
a
chronic
brain
degenerative
that
leads
to
dementia.
Objective
The
aim
of
the
present
study
investigate
neuroprotective
impact
sodium-glucose
cotransporter-2
inhibitors
(SGLT2i)
(empagliflozin
and
dapagliflozin)
on
tau
phosphorylation,
oxidative
stress,
neuroinflammation.
Methods
We
used
MTT
(3-(4,
5-dimethylthiazolyl-2)-2,
5-diphenyltetrazolium
bromide)
assay,
annexin-V-FITC
kit,
DCFH-DA
(dichloro-dihydro-fluorescein
diacetate)
respectively
evaluate
effect
SGLT2i
amyloid-β
(Aβ)
1–42
-induced
neuronal
death,
apoptosis,
stress.
expression
NLRP3-inflammasome,
phospho-Tau181,
glycogen
synthase
kinase-3
beta
(GSK-3β),
cyclin-dependent
kinase
5
(CdK5),
histone
deacetylase
6
(HDAC6),
was
quantified
by
flow
cytometry.
Drug
distribution
in
mice's
brains
assessed
liquid
chromatography-mass
spectrometry
(LC-MS).
Results
Aβ
significantly
reduced
cell
viability
increased
which
reversed
using
gliflozins.
reactive
oxygen
species
generation,
downregulated
diminished
pathology.
Mechanistically,
last
involved
modulation
GSK-3β
CdK5
protein
expression.
However,
tested
treatments
did
not
modify
-stimulating
HDAC6.
Gliflozins
are
substrates
drug
transporters
ATP-binding
cassette
sub-family
B
member
1
and/or
ATP
binding
subfamily
G
2
(ABCB1
ABCG2),
Elacridar
enhances
their
distribution.
Conclusions
empagliflozin
dapagliflozin
exhibited
actions
against
human
neurotoxicity.
Inflammopharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 3, 2025
Abstract
The
currently
approved
drugs
for
Alzheimer’s
disease
(AD)
are
only
symptomatic
treatment
in
the
early
stages
of
but
they
could
not
halt
neurodegeneration,
additionally,
safety
profile
recently
developed
immunotherapy
is
a
big
issue.
This
review
aims
to
explain
importance
repurposing
technique
and
strategy
develop
therapy
AD.
We
illustrated
biological
alterations
pathophysiology
AD
including
amyloid
pathology,
Tau
oxidative
stress,
mitochondrial
dysfunction,
neuroinflammation,
glutamate-mediated
excitotoxicity,
insulin
signaling
impairment,
wingless-related
integration
site/
β
-catenin
signaling,
autophagy.
Additionally,
we
demonstrated
different
repurposed
experimental
models
anti-inflammatory,
anti-hypertensive,
anti-diabetic,
antiepileptic,
antidepressant
anticancer
drugs.
Further,
showed
pipeline
FDA
have
promising
therapeutic
activity
against
AD,
confirming
value
elucidate
curative
Graphical
abstract
Current Alzheimer Research,
Год журнала:
2024,
Номер
21(2), С. 141 - 154
Опубликована: Фев. 1, 2024
Background:
As
individuals
age,
they
may
develop
Alzheimer's
disease
(AD),
which
is
characterized
by
difficulties
in
speech,
memory
loss,
and
other
issues
related
to
neural
function.
Cycloastragenol
an
active
ingredient
of
Astragalus
trojanus
has
been
used
treat
inflammation,
aging,
heart
disease,
cancer.
Objectives:
This
study
aimed
explore
the
potential
therapeutic
benefits
cycloastragenol
rats
with
experimentally
induced
AD.
Moreover,
underlying
molecular
mechanisms
were
also
evaluated
measuring
Nrf2
HO-1,
are
involved
oxidative
stress,
NFκB
TNF-α,
BCL2,
BAX,
caspase-3,
apoptosis.
Methods:
Sprague-Dawley
given
70
mg/kg
aluminum
chloride
intraperitoneally
daily
for
six
weeks
induce
Following
AD
induction,
25
oral
gavage
three
weeks.
Hippocampal
sections
stained
hematoxylin/
eosin
anti-caspase-3
antibodies.
The
Nrf2,
NFκB,
caspase-3
gene
expressions
protein
levels
samples
analyzed.
Results:
significantly
improved
rats'
behavioral
test
performance.
It
strengthened
organization
hippocampus.
performance
hippocampal
structure
rats.
caused
a
marked
decrease
expression
was
associated
increase
HO-1.
Conclusion:
hippocampus
enhanced
outcomes
tests,
decreased
concentration
AChE
brain,
exerted
antioxidant
anti-inflammatory
effects.
Antiapoptotic
effects
noted,
leading
significant
improvements
cognitive
function,
memory,
behavior
treated
Pharmaceuticals,
Год журнала:
2023,
Номер
16(11), С. 1620 - 1620
Опубликована: Ноя. 16, 2023
The
incidence
of
neurodegenerative
diseases,
such
as
Alzheimer’s
disease
(AD),
is
continuously
growing
worldwide,
which
leads
to
a
heavy
economic
and
societal
burden.
lack
safe
effective
causal
therapy
in
cognitive
decline
an
aggravating
factor
requires
investigations
into
the
repurposing
commonly
used
drugs.
Sodium-glucose
co-transporter
2
inhibitors
(SGLT2i)
are
new
efficient
class
hypoglycemic
drugs
and,
due
their
pleiotropic
effects,
have
indications
that
go
beyond
diabetes.
There
emerging
data
from
murine
studies
SGLT2i
can
cross
blood–brain
barrier
may
neuroprotective
increasing
brain-derived
neurotrophic
(BDNF),
reducing
amyloid
burden,
inhibiting
acetylcholinesterase
(AChE)
restoring
circadian
rhythm
mammalian
target
rapamycin
(mTOR)
activation.
current
study
investigates
effect
donepezil,
under
separate
or
combined
21-day
treatment
on
AD-relevant
behaviors
brain
pathology
mice.
canagliflozin
was
found
significantly
improve
novelty
preference
index
percentage
time
spent
open
arms
maze
novel
object
recognition
elevated
plus
test,
respectively.
In
addition,
decreased
AChE
activity,
mTOR
glial
fibrillary
acidic
protein
expression.
results
also
recorded
acetylcholine
M1
receptor
canagliflozin-treated
mice
compared
scopolamine
group.
hippocampus,
reduced
microgliosis
astrogliosis
males,
but
not
female
These
findings
emphasize
value
clinical
practice.
By
represents
compound
resembles
AD-registered
therapies
this
respect,
supporting
need
for
further
evaluation
dementia
trials.
