Unveiling the mechanism of amelioration of adjuvant-induced rheumatoid arthritis by Drynaria quercifolia rhizome extract using network pharmacology and gene expression-based studies
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Апрель 8, 2025
Rhizomes
of
Drynaria
quercifolia
have
long
been
traditionally
used
to
manage
rheumatic
pain.
However,
there
is
limited
research
supporting
this
traditional
practice
and
insufficient
evidence
demonstrating
the
molecular
mechanisms
action
plant-derived
bioactives
in
rheumatoid
arthritis
(RA).
The
current
study
aims
identify
effective
components
methanol
rhizome
extract
(DME)
their
probable
pharmacological
alleviating
Rheumatoid
Arthritis
(RA)
using
network-pharmacology,
docking,
molecular-dynamics
simulations,
gene
expression-based
validation.
Gas
chromatography-mass
spectrometry
(GC-MS)
based
screening
identified
41
volatile
phytocomponents
from
DME
having
drug-like
potentiality.
Network
pharmacology-based
revealed
117
therapeutic
targets
for
RA
which
11
as
core
targets.
Gene
Ontology
(GO)
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
enrichment
analysis
indicated
that
key
target
genes
were
mostly
enriched
inflammatory
response
associated
with
multiple
signalling
pathways.
Molecular
docking
dynamics
studies
proteins
like
serine/threonine-protein
kinase
(AKT1),
peroxisome
proliferator-activated
receptor
alpha
(PPARA),
gamma
(PPARG),
exhibited
strong
binding
affinity
stable
interactions
present
DME.
For
experimental
verification
FCA
(Freund's
complete
adjuvant)-induced
chronic
model
employed
further
investigation.
Quantitative
reverse
transcription
polymerase
chain
reaction
(qRT-PCR)
results
validated
significantly
(p
≤
0.05)
regulate
expression
AKT
PPARG
model.
Moreover,
confirmed
downregulated
pro-inflammatory
mediators
COX-2,
IL-6
TNF-α
at
protein
levels
also
normalized
different
oxidative
stress
parameters
both
low
high
dose
groups
DME-treated
arthritic
animals.
In
conclusion,
network-based
silico
approach
probably
act
a
synergistic
way
modulate
RA,
was
by
studies.
Therefore,
could
be
potential
alternative
immunomodulatory
therapies
combat
related
conditions.
Язык: Английский
Rhaponticin Alleviates Collagen-induced Arthritis by Inhibiting NLRP3/GSDMD-mediated Neutrophil Extracellular Traps
Inflammation,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 27, 2024
Neutrophil
extracellular
traps
(NETs)
play
an
important
role
in
the
inflammatory
response
and
progressive
joint
destruction
rheumatoid
arthritis
(RA).
Rhaponticin
(Rha)
is
a
stilbene
glycoside
compound
with
antioxidant
anti-inflammatory
effects.
This
study
aimed
to
investigate
therapeutic
potential
of
Rha
RA,
specific
focus
on
its
effects
NETs
underlying
mechanisms
Rha.
formation
induced
by
phorbol
12-myristate
13-acetate
(PMA)
collagen-induced
(CIA)
mouse
model
were
implemented
evaluate
pharmacological
vitro
vivo.
The
mechanism
improving
RA
was
screened
verified
using
SuperPred
DisGeNET
databases.
Disulfiram
(a
GSDMD
inhibitor)
S100a8cre
GSDMDfl/fl
mice
used
confirm
whether
key
findings
demonstrate
that
significantly
inhibited
reactive
oxygen
species
production
PMA-activated
neutrophils.
In
vivo,
treatment
relieved
symptoms
CIA
production.
Mechanistically,
reduced
via
inhibition
NLRP3/GSDMD
activation.
Neutrophil-specific
depletion
eliminated
vitro.
alleviated
inflammation
vivo
Overall,
our
results
indicated
exerts
protective
effect
against
inhibiting
through
pathway.
this
provide
new
strategies
for
treating
RA.
Язык: Английский