Combining vinpocetine or cocoa with levodopa, Coenzyme Q10 and vitamin B complex mitigates rotenone-induced Parkinson’s disease in rats: Impact on Nrf2/HO-1, NF-kB, AMPK/SIRT-1/Beclin-1, AKT/GSK-3β/CREB/BDNF and Apoptotic Pathways
Biomedicine & Pharmacotherapy,
Год журнала:
2025,
Номер
186, С. 118011 - 118011
Опубликована: Март 31, 2025
Язык: Английский
Targeting Ferroptosis in Parkinson’s: Repurposing Diabetes Drugs as a Promising Treatment
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1516 - 1516
Опубликована: Фев. 11, 2025
This
review
explores
the
promising
potential
of
repurposing
type
2
diabetes
(T2D)
medications
for
treatment
Parkinson's
disease
(PD),
highlighting
shared
pathophysiological
mechanisms
between
these
two
age-related
conditions,
such
as
oxidative
stress,
mitochondrial
dysfunction,
and
ferroptosis.
The
overlap
suggests
that
existing
drugs
could
target
common
pathways
involved
in
both
conditions.
Specifically,
discusses
how
T2D
medications,
including
metformin
(Met),
peroxisome-proliferator-activated
receptor
gamma
(PPAR-γ)
agonists,
sodium-glucose
cotransporter-2
(SGLT2)
inhibitors,
incretins,
dipeptidyl-peptidase
4
(DPP-4)
can
improve
function,
reduce
neuroinflammation
potentially
inhibit
connection
ferroptosis
treatments,
medication,
are
only
beginning
to
be
explored.
limited
data
attributed
also
complexity
fact
specific
role
pathogenesis
has
not
been
a
primary
focus
until
recent.
Despite
preclinical
evidence,
clinical
findings
mixed,
underscoring
need
further
research
elucidate
drugs'
roles
neurodegeneration.
Repurposing
have
well-established
safety
profiles
significantly
time
cost
associated
with
drug
development
offer
more
comprehensive
approach
managing
compared
treatments
targeting
single
mechanism.
Язык: Английский
The Effect of mitochondrial-associated endoplasmic reticulum membranes (MAMs) modulation: New insights into therapeutic targets for depression
Neuroscience & Biobehavioral Reviews,
Год журнала:
2025,
Номер
unknown, С. 106087 - 106087
Опубликована: Март 1, 2025
Язык: Английский
GIP/GLP-1 DUAL AGONIST TIRZEPATIDE AMELIORATES RENAL ISCHEMIA/REPERFUSION DAMAGE IN RATS
International Journal of Applied Pharmaceutics,
Год журнала:
2025,
Номер
unknown, С. 165 - 173
Опубликована: Март 7, 2025
Objective:
Renal
Ischemia/Reperfusion
Injury
(RIRI)
initiates
a
cascade
of
deleterious
events
resulting
in
acute
kidney
injury
with
high
mortality
rates.
Tirzepatide
has
anti-inflammatory,
anti-apoptotic
and
antioxidant
as
well
activation
both
autophagy
Protein
Kinase
B
(PKB
or
Akt)
signaling
pathway.
This
study
examines
the
potential
nephroprotective
effect
tirzepatide
against
RIRI
rats.
Methods:
Twenty-eight
male
rats
(Sprague
Dawley)
were
split
into
four
groups:
sham,
(IRI),
Distilled
Water
(D.
W)
tirzepatide.
The
Sham
group
underwent
identical
procedures
without
bilateral
renal
pedicle
clamping,
whereas
IRI
was
exposed
to
30
min
ischemia
followed
by
24
h
reperfusion.
vehicle
received
distilled
water
intraperitoneally
2
before
ischemia,
3
mg/kg
ischemia.
Study
parameters
including
urea,
creatinine,
Kidney
Molecule-1
(KIM-1),
interleukin-6
(IL-6),
caspase-3,
Akt,
autophagic
protein
microtubule-associated
1
light
chain
3-B
(LC3-B)
glutathione
(GSH),
histopathological
changes
examined.
Results:
resulted
significant
elevation
serum
creatinine
levels
KIM-1,
IL-6,
LC3-B
while
concurrently
reduction
GSH
level.
treatment
diminished
severity
damage
alleviating
inflammatory
apoptotic
markers,
augmenting
activity
improving
consequences.
Conclusion:
elucidates
effects
RIRI,
via
its
antioxidant,
antiapoptotic
properties
Akt
Язык: Английский
Monotropein alleviates septic acute liver injury by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway
International Immunopharmacology,
Год журнала:
2024,
Номер
142, С. 113178 - 113178
Опубликована: Сен. 20, 2024
Язык: Английский
Advances in the clinical treatment of multidrug-resistant pathogens using polymyxins
Journal of Antimicrobial Chemotherapy,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 1, 2024
Abstract
Objectives
Polymyxins
are
a
vital
class
of
antibiotics
used
to
combat
multidrug-resistant
Gram-negative
bacteria.
However,
their
use
is
limited
due
potential
nephrotoxicity
and
the
availability
alternative
antibiotics.
This
review
aims
examine
properties
polymyxins
clinical
advances
in
for
treating
infections
caused
by
carbapenem-resistant
bacteria
(CR-GNB).
Methods
analyses
literature
on
polymyxin
various
approaches,
including
intravenous
drip
infusion,
nebulized
or
dry
powder
inhalation,
ointment
application.
Treatment
efficacy
terms
bacterial
eradication,
cure
rate
mortality
reviewed
evaluated.
Results
have
been
reintroduced
treat
critical
increasing
prevalence
CR-GNB.
Clinical
trials
studies
confirmed
that
can
effectively
CR-GNB
when
formulation
administration
appropriate,
with
acceptable
levels
nephrotoxicity.
Conclusions
In
future,
development
formulations
will
aim
improve
effectiveness
while
reducing
toxicity
side
effects
preventing
emergence
polymyxin-resistant
strains.
Enhanced
minimized
be
achieved
developing
new
polymyxin-delivery
systems
provide
smart
controlled
release
customized
patient
administration.
Язык: Английский
Colistin Induces Oxidative Stress and Apoptotic Cell Death through the Activation of the AhR/CYP1A1 Pathway in PC12 Cells
Antioxidants,
Год журнала:
2024,
Номер
13(7), С. 827 - 827
Опубликована: Июль 10, 2024
Colistin
is
commonly
regarded
as
the
"last-resort"
antibiotic
for
combating
life-threatening
infections
caused
by
multidrug-resistant
(MDR)
gram-negative
bacteria.
Neurotoxicity
a
potential
adverse
event
associated
with
colistin
application
in
clinical
settings,
yet
exact
molecular
mechanisms
remain
unclear.
This
study
examined
detrimental
impact
of
exposure
on
PC12
cells
and
mechanisms.
treatment
at
concentrations
0-400
μM
decreased
cell
viability
induced
apoptotic
death
both
time-
concentration-dependent
manners.
Exposure
to
triggered
production
reactive
oxygen
species
(ROS)
oxidative
stress
damage
cells.
N-acetylcysteine
(NAC)
supplementation
partially
mitigated
cytotoxic
outcomes
colistin.
Evidence
mitochondrial
dysfunction
was
observed
through
dissipation
membrane
potential.
Additionally,
upregulated
expression
AhR
CYP1A1
mRNAs
Pharmacological
inhibition
(e.g.,
using
α-naphthoflavone)
or
intervention
gene
significantly
ROS
colistin,
subsequently
lowering
caspase
activation
apoptosis.
In
conclusion,
our
findings
demonstrate,
first
time,
that
AhR/CYP1A1
pathway
contributes
colistin-induced
apoptosis,
offering
insights
into
effects
Язык: Английский
Adropin/Tirzepatide Combination Mitigates Cardiac Metabolic Aberrations in a Rat Model of Polycystic Ovarian Syndrome, Implicating the Role of the AKT/GSK3β/NF-κB/NLRP3 Pathway
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
26(1), С. 1 - 1
Опубликована: Дек. 24, 2024
Polycystic
ovarian
syndrome
(PCOS)
is
a
multifaceted
metabolic
and
hormonal
disorder
in
females
of
reproductive
age,
frequently
associated
with
cardiac
disturbances.
This
research
aimed
to
explore
the
protective
potential
adropin
and/or
tirzepatide
(Tirze)
on
cardiometabolic
aberrations
letrozole-induced
PCOS
model.
Female
Wistar
non-pregnant
rats
were
allotted
into
five
groups:
CON;
PCOS;
+
adropin;
Tirze;
adropin+
Tirze.
The
serum
sex
hormones,
glucose,
lipid
profiles
securitized.
Cardiac
phosphorylated
levels
AKT(pAKT),
glycogen
synthase
kinase-3
beta
(pGSK-3β),
NOD-like
receptor
family
pyrin
domain
containing
3
(NLPR3),
IL-1β
IL-18
assayed.
redox
status
endoplasmic
reticulum
stress
(ER)
parameters
including
relative
glucose-regulated
protein
78
(GRP78)
C/EBP
homologous
(CHOP)
gene
expressions
detected.
Finally,
immunoreactivity
NF-κB,
Bcl2,
BAX
assessed.
Our
results
displayed
that
Tirze
intervention
successfully
alleviated
PCOS-provoked
derangements
better
recorded
for
combination
treatment.
synergistic
effect
mostly
mediated
via
activating
Akt,
which
dampens
GSK3β/NF-κB/NLRP3
signaling
pathway,
sequel
alleviating
oxidative
damage,
inflammatory
response,
ER
stress,
related
apoptosis,
making
them
alluring
desirable
therapeutic
targets
PCOS-associated
complications.
Язык: Английский