Abstract
Nuclear
factor
erythroid
2‐related
(Nrf2)
is
a
cytoprotective
transcription
that
induces
the
of
genes
responsible
for
cell's
response
to
oxidative
stress.
While
Nrf2
activation
has
led
development
clinically
relevant
therapeutics,
oncogenic
role
in
proliferation
cancer
cells
underscored
complex
nature
and
necessity
inhibitors.
Although
application
inhibitors
appears
limited
as
anticancer
agents,
recent
studies
have
begun
pinpoint
impairment
autophagy
diseases
cellular
marker
shifts
from
protective
deleterious
state.
Therefore,
cytoplasmic
accumulation
can
lead
lipid
hydroperoxides
and,
ultimately,
ferroptosis.
However,
some
aimed
at
elucidating
non‐cancer
yielded
conflicting
results,
attributed
differences
approaches
used
inhibit
or
activate
Nrf2,
well
variations
vitro
and/or
vivo
disease
models.
Overall,
these
results
highlight
deeper
evaluation
Nrf2′s
diseases,
especially
chronic
diseases.
In
this
review,
we
discuss
where
inhibition
holds
potential
beneficial
therapeutic
effects
summarize
recently
reported
exploiting
medicinal
chemistry
suitable
targeting
factors
like
Nrf2.
Molecules,
Год журнала:
2024,
Номер
29(12), С. 2832 - 2832
Опубликована: Июнь 14, 2024
This
study
investigated
the
mechanism
by
which
fucoxanthin
acts
as
a
novel
ferroptosis
inducer
to
inhibit
tongue
cancer.
The
MTT
assay
was
used
detect
inhibitory
effects
of
on
SCC-25
human
squamous
carcinoma
cells.
levels
reactive
oxygen
species
(ROS),
mitochondrial
membrane
potential
(MMP),
glutathione
(GSH),
superoxide
dismutase
(SOD),
malondialdehyde
(MDA),
and
total
iron
were
measured.
Reverse
transcription-quantitative
polymerase
chain
reaction
(RT-qPCR)
Western
blotting
assess
peroxidase
4
(GPX4),
nuclear
factor
erythroid
2-related
2
(Nrf2),
Keap1,
solute
carrier
family
7
member
11
(SLC7A11),
transferrin
receptor
protein
1
(TFR1),
p53,
heme
oxygenase
(HO-1)
expression.
Molecular
docking
performed
validate
interactions.
Compared
with
control
group,
activity
fucoxanthin-treated
cells
significantly
decreased
in
dose-
time-dependent
manner.
MMP,
GSH,
SOD
cells;
ROS,
MDA,
increased.
mRNA
expression
GPX4,
Nrf2,
HO-1
decreased,
whereas
TFR1
p53
increased,
concentration-dependent
analysis
revealed
that
binding
free
energies
SLC7A11,
HO-1,
below
-5
kcal/mol,
primarily
based
active
site
hydrogen
bonding.
Our
findings
suggest
can
induce
cells,
highlighting
its
treatment
for
Redox Biology,
Год журнала:
2024,
Номер
76, С. 103324 - 103324
Опубликована: Авг. 23, 2024
The
polarization
phenotype
of
microglia
is
critical
in
the
progression
Parkinson's
disease
(PD).
Molecules
that
can
polarize
toward
M2
represent
a
promising
class
compounds
for
anti-PD
medications.
Z-ligustilide
(ZLG)
naturally
occurring
enol
ester
with
diverse
pharmacological
properties,
especially
neuroprotection.
For
first
time,
we
investigated
effect
ZLG
on
and
elucidated
its
underlying
mechanism.
results
primarily
showed
attenuated
motor
deficits
mice
prevented
loss
dopaminergic
neurons
substantia
nigra.
Mechanistically,
alleviates
oxidative
stress-induced
apoptosis
by
triggering
endogenous
antioxidant
system.
Besides,
modulated
phenotypic
through
activation
Nrf2-TrxR
axis,
leading
to
towards
phenotype.
Taken
together,
our
research
prospective
therapy
candidate
PD
altering
restoring
redox
equilibrium
axis.
Xenobiotica,
Год журнала:
2025,
Номер
unknown, С. 1 - 30
Опубликована: Фев. 11, 2025
The
Nrf2
signaling
pathway
is
crucial
for
cellular
defense
against
oxidative
stress
and
xenobiotic
toxicity,
highlighting
its
importance
in
both
human
health
environmental
responses.
Ferroptosis,
an
iron-dependent
form
of
regulated
cell
death,
is
driven
by
lipid
peroxidation
and
shaped
metabolic
antioxidant
pathways.
In
immune
cells,
ferroptosis
susceptibility
varies
types,
composition,
demands,
influencing
responses
in
cancer,
infections,
autoimmune
diseases.
Therapeutically,
targeting
holds
promise
cancer
immunotherapy
enhancing
antitumor
immunity
or
inhibiting
immunosuppressive
cells.
This
review
highlights
the
pathways
underlying
ferroptosis,
its
regulation
dual
role
tumor
progression
immunity,
context-dependent
therapeutic
implications
for
optimizing
treatment.
