International Journal of Biological Sciences,
Journal Year:
2023,
Volume and Issue:
19(9), P. 2678 - 2694
Published: Jan. 1, 2023
Diabetic
kidney
disease
(DKD)
is
one
of
the
most
common
and
severe
microvascular
complications
diabetes
mellitus
(DM),
has
become
leading
cause
end-stage
renal
(ESRD)
worldwide.Although
exact
pathogenic
mechanism
DKD
still
unclear,
programmed
cell
death
been
demonstrated
to
participate
in
occurrence
development
diabetic
injury,
including
ferroptosis.Ferroptosis,
an
iron-dependent
form
driven
by
lipid
peroxidation,
identified
play
a
vital
role
therapeutic
responses
variety
diseases,
such
as
acute
injury
(AKI),
carcinoma
DKD.In
past
two
years,
ferroptosis
well
investigated
patients
animal
models,
but
specific
mechanisms
effects
have
not
fully
revealed.Herein,
we
reviewed
regulatory
ferroptosis,
summarized
recent
findings
associated
with
involvement
DKD,
discussed
potential
promising
target
for
treatment,
thereby
providing
valuable
reference
basic
study
clinical
therapy
DKD.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: May 23, 2024
Ferroptosis
is
a
non-apoptotic
mode
of
programmed
cell
death
characterized
by
iron
dependence
and
lipid
peroxidation.
Since
the
ferroptosis
was
proposed,
researchers
have
revealed
mechanisms
its
formation
continue
to
explore
effective
inhibitors
in
disease.
Recent
studies
shown
correlation
between
pathological
neurodegenerative
diseases,
as
well
diseases
involving
tissue
or
organ
damage.
Acting
on
ferroptosis-related
targets
may
provide
new
strategies
for
treatment
ferroptosis-mediated
diseases.
This
article
specifically
describes
metabolic
pathways
summarizes
reported
action
natural
synthetic
small
molecule
their
efficacy
The
paper
also
treatments
such
gene
therapy,
nanotechnology,
summarises
challenges
encountered
clinical
translation
inhibitors.
Finally,
relationship
other
modes
discussed,
hopefully
paving
way
future
drug
design
discovery.
Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
30(1)
Published: May 26, 2024
Abstract
Diabetes
mellitus,
a
chronic
metabolic
disease,
often
leads
to
numerous
complications,
significantly
contributing
global
morbidity
and
mortality
rates.
High
glucose
levels
trigger
epigenetic
modifications
linked
pathophysiological
processes
like
inflammation,
immunity,
oxidative
stress,
mitochondrial
dysfunction,
senescence
various
kinds
of
cell
death.
Despite
glycemic
control,
transient
hyperglycemia
can
persistently
harm
organs,
tissues,
cells,
latent
effect
termed
"metabolic
memory"
that
contributes
diabetic
complications.
Understanding
memory's
mechanisms
could
offer
new
approach
mitigating
these
However,
key
molecules
networks
underlying
memory
remain
incompletely
understood.
This
review
traces
the
history
research,
highlights
its
features,
discusses
recent
involved
in
mechanisms,
summarizes
confirmed
potential
therapeutic
compounds.
Additionally,
we
outline
vitro
vivo
models
memory.
We
hope
this
work
will
inform
future
research
on
regulatory
facilitate
development
effective
compounds
prevent
Drug Development Research,
Journal Year:
2025,
Volume and Issue:
86(1)
Published: Jan. 12, 2025
ABSTRACT
Naringenin
has
the
potential
to
regulate
ferroptosis
and
mitigate
renal
damage
in
diabetic
nephropathy
(DN).
However,
it
remains
unclear
whether
naringenin's
effects
DN
are
linked
its
ability
ferroptosis.
This
study
investigated
anti‐ferroptosis
properties
of
naringenin
high
glucose
(HG)‐induced
tubular
epithelial
cell
models.
HK‐2
cells
were
cultured
HG
medium
establish
model.
treated
with
different
doses
explore
effect
naringenin.
The
CCK‐8
results
show
that
50
μM
~
200
do
not
affect
viability
HG‐induced
increase
a
dose‐dependent
manner
treatment.
Additionally,
increased
levels
IL‐10
while
decreasing
IL‐1β,
TNF‐α,
IL‐6,
ROS
cells.
also
reduced
Fe
2+
,
oxidized
lipid
ROS,
MDA,
4‐HNE,
ACSL4,
TFR1
cells,
increasing
non‐oxidized
SOD,
GSH‐Px,
SLC7A11,
GPX4.
Meanwhile,
restored
MMP,
ATP
MPTP
opening,
OCR
Furthermore,
reversed
decreased
expression
SIRT1,
p‐FOXO3a,
Nrf2
Nuclear
caused
by
HG.
SIRT1
inhibitor
EX527
ML385
attenuated
on
demonstrating
stronger
reversal
than
ML385.
These
suggest
inhibits
mainly
through
SIRT1/FOXO3a
signaling
pathway.
finding
further
enhanced
our
understanding
mechanism
behind
protective
DN.
The
management
of
diabetic
wounds
faces
significant
challenges
due
to
the
excessive
activation
reactive
oxygen
species
(ROS),
dysregulation
inflammatory
response,
and
impaired
angiogenesis.
A
substantial
body
evidence
suggests
that
aforementioned
diverse
factors
contributing
delayed
healing
may
be
associated
with
autophagy.
Impaired
autophagy
leads
endothelial
fibroblast
dysfunction
impedes
macrophage
phenotypic
transformation.
This
disruption
hinders
angiogenesis
extracellular
matrix
deposition,
ultimately
culminating
in
wound
healing.
Therefore,
biomaterials
possessing
regulatory
functions
hold
potential
for
clinical
applications
enhancing
wounds.
hybrid
multifunctional
hydrogel
(GelMa@SIS-Qu)
has
been
developed,
comprising
methacrylamide
gelatin
(GelMa),
a
small
intestine
submucosal
acellular
(SIS),
quercetin
nanoparticles,
which
demonstrates
capability
promote
promotion
not
only
reduces
ROS
levels
cells
enhances
their
antioxidant
activity
but
also
mitigates
ROS-induced
cell
apoptosis,
thereby
promoting
Furthermore,
facilitates
transformation
macrophages
from
M1
phenotype
M2
phenotype.
study
investigates
distinctive
mechanisms
GelMa@SIS-Qu
proposes
promising
therapeutic
strategy
treating
diabetes-related
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
15
Published: Feb. 19, 2025
It
has
been
regarded
as
an
essential
treatment
option
for
diabetic
nephropathy
(DN)
in
Traditional
Chinese
medicine.
Previous
studies
have
demonstrated
the
anti-DN
efficacy
of
Schisandra
chinensis
Fruit
Mixture
(SM);
however,
a
comprehensive
chemical
fingerprint
is
still
uncertain,
and
its
mechanism
action,
especially
potential
therapeutic
targets
anti-DN,
needs
to
be
further
elucidated.
Potential
mechanisms
SM
action
on
DN
were
explored
through
network
pharmacology
experimental
validation.
The
composition
was
analyzed
using
UPLC-ESI-MS/MS
technology.
Active
bioactive
components
identified
TCMSP,
SwissDrugDesign,
SymMap
platforms.
Differentially
expressed
genes
determined
microarray
gene
data
from
GSE30528
dataset.
Related
obtained
online
databases,
which
include
GeneCards,
OMIM
DisGeNET.
PPI
networks
compound-target-pathway
constructed
Cytoscape.
Functional
annotation
performed
R
software
GO
enrichment
KEGG
pathway
analysis.
model
built
validation
high-sugar
high-fat
diet
combined
with
STZ
induction.
Hub
critical
signaling
pathways
detected
qPCR,
Western
blotting
immunofluorescence.
Utilizing
coupling
technique,
analysis
1281
SM's
ethanol
extract,
349
these
recognized
compounds
pharmacology.
Through
this
analysis,
126
shared
15
HUB
pinpointed.
Of
these,
JAK2
most
gene.
Enrichment
revealed
that
primarily
operates
within
PI3K/AKT
pathway.
In
vivo
experiments
confirmed
improved
pathological
injury
renal
function
rats
while
improving
mitochondrial
morphology
modulating
expression
proteins
linked
apoptosis
(cleaved-caspase-3,
Bax,
Bcl-2)
pro-inflammatory
factors
(IL-6
TNF-α).
Mechanistically,
alleviates
by
suppressing
PI3K/AKT/mTOR
JAK2/STAT3
fulfill
energy
tissues.
Furthermore,
molecular
docking
provided
direct
findings.
findings
study
offer
initial
indications
active
component
robust
anti-inflammatory
anti-apoptotic
characteristics
mitigation
DN,
along
capacity
safeguard
integrity
functionality
mitochondria.
This
research
unequivocally
validates
favorable
effects
SM,
indicating
viable
pharmaceutical
agent
management
DN.
Advanced Science,
Journal Year:
2023,
Volume and Issue:
11(10)
Published: Dec. 25, 2023
Abstract
Diabetic
nephropathy
(DN)
is
a
serious
microvascular
complication
of
diabetes.
Ferroptosis,
new
form
cell
death,
plays
crucial
role
in
the
pathogenesis
DN.
Renal
tubular
injury
triggered
by
ferroptosis
might
be
essential
this
process.
Numerous
studies
demonstrate
that
vitamin
D
receptor
(VDR)
exerts
beneficial
effects
suppressing
ferroptosis.
However,
underlying
mechanism
has
not
been
fully
elucidated.
Thus,
they
verified
nephroprotective
effect
VDR
activation
and
explored
which
suppressed
db/db
mice
high
glucose‐cultured
proximal
epithelial
cells
(PTECs).
Paricalcitol
(PAR)
agonist
can
mitigate
kidney
prevent
renal
dysfunction.
PAR
treatment
could
inhibit
PTECs
through
decreasing
iron
content,
increasing
glutathione
(GSH)
levels,
reducing
malondialdehyde
(MDA)
generation,
expression
positive
mediator
transferrin
1
(TFR‐1),
enhancing
negative
mediators
including
ferritin
heavy
chain
(FTH‐1),
peroxidase
4
(GPX4),
cystine/glutamate
antiporter
solute
carrier
family
7
member
11
(SLC7A11).
Mechanistically,
upregulated
NFE2‐related
factor
2/heme
oxygenase‐1
(Nrf2/HO‐1)
signaling
pathway
to
suppress
PTECs.
These
findings
suggested
inhibited
DN
via
modulating
Nrf2/HO‐1
pathway.
International Journal of Biological Sciences,
Journal Year:
2023,
Volume and Issue:
19(12), P. 3726 - 3743
Published: Jan. 1, 2023
Ferroptosis
is
an
iron-dependent
programmed
cell
death
pattern
that
characterized
by
iron
overload,
reactive
oxygen
species
(ROS)
accumulation
and
lipid
peroxidation.
Growing
viewpoints
support
the
imbalance
of
homeostasis
disturbance
metabolism
contribute
to
tissue
or
organ
injury
in
various
kidney
diseases
triggering
ferroptosis.
At
present,
key
regulators
complicated
network
mechanisms
associated
with
ferroptosis
have
been
deeply
studied;
however,
its
role
initiation
progression
has
not
fully
revealed.
Herein,
we
aim
discuss
features,
ferroptosis,
explore
emerging
roles
organelles
gather
pharmacological
progress,
systematically
summarize
most
recent
discoveries
about
crosstalk
between
diseases,
including
renal
carcinoma
(RCC),
acute
(AKI),
diabetic
disease
(DKD),
autosomal
dominant
polycystic
(ADPKD),
fibrosis,
lupus
nephritis
(LN)
IgA
nephropathy.
We
further
conclude
potential
therapeutic
strategies
targeting
for
prevention
treatment
hope
this
work
will
provide
insight
study
pathogenesis
kidney-related
diseases.
