Evaluation of the Anti-Mycobacterial and Anti-Inflammatory Activities of the New Cardiotonic Steroid γ-Benzylidene Digoxin-15 in Macrophage Models of Infection
Microorganisms,
Год журнала:
2025,
Номер
13(2), С. 269 - 269
Опубликована: Янв. 25, 2025
Cardiotonic
steroids
modulate
various
aspects
of
the
inflammatory
response.
The
synthetic
cardiotonic
steroid
γ-benzylidene
digoxin
15
(BD-15),
a
derivative,
has
emerged
as
promising
candidate
with
potential
immunomodulatory
effects.
However,
its
biological
activity
remains
largely
unexplored.
This
study
investigated
anti-mycobacterial
and
anti-inflammatory
effects
BD-15
in
an
vitro
macrophage
infection
model
Mycobacterium
spp.
Unlike
digoxin,
which
showed
significant
toxicity
at
higher
concentrations,
exhibited
no
cytotoxicity
RAW
264.7
cells
(a
murine
cell
line).
Both
compounds
were
evaluated
smegmatis-infected
cells,
reducing
bacterial
burden
without
direct
bactericidal
activity.
Additionally,
both
modulated
pro-inflammatory
cytokine
levels,
notably
by
decreasing
tumor
necrosis
factor
alpha
(TNF-α)
interleukin-1
beta
(IL-1β)
levels.
specifically
reduced
NOD-,
LRR-,
pyrin-domain-containing
protein
3
(NLRP3)
inflammasome
expression
increased
interleukin-10
(IL-10)
production.
Notably,
colony-forming
unit
(CFU)
counts
tuberculosis-infected
cells.
Toxicity
assays
HepG2
human
liver
cancer
line)
that
had
minimal
hepatotoxicity
compared
to
demonstrated
negligible
acute
Artemia
salina
bioassay.
These
findings
revealed
highlighted
safer
alternative
for
therapeutic
applications.
Язык: Английский
Evaluation of the neuroprotective potential of benzylidene digoxin 15 against oxidative stress in a neuroinflammation models induced by lipopolysaccharide and on neuronal differentiation of hippocampal neural precursor cells
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Март 14, 2025
Neuroinflammation,
often
driven
by
the
overproduction
of
reactive
oxygen
species
(ROS),
plays
a
crucial
role
in
pathogenesis
neurodegenerative
diseases
such
as
Alzheimer's
and
Parkinson's
diseases.
The
susceptibility
brain
to
oxidative
stress
is
attributed
its
high
metabolic
activity
limited
antioxidant
defense.
This
study
aimed
evaluate
neuroprotective
potential
Benzylidene
Digoxin
15
(BD-15)
following
treatment
pretreatment
lipopolysaccharide
(LPS)-induced
neuroinflammation
model.
Additionally,
we
examined
whether
BD-15
enhances
generation
neurons
from
neural
progenitor
cells
(NPCs).Male
Wistar
rats
were
used
for
acute
studies
divided
into
four
groups:
control
(saline),
(100
μg/kg),
LPS
(250
+
μg/kg
100
μg/kg).
Swiss
albino
mice
chronic
(0.56
mg/kg),
(1
mg/kg
0.56
mg/kg).
Behavioral
changes
assessed
using
open
field
test,
tissues
analyzed
markers,
including
malondialdehyde
(MDA),
reduced
glutathione
(GSH),
protein
carbonylation,
catalase
(CAT),
superoxide
dismutase
(SOD),
S-transferase
(GST).
To
assess
neurogenesis,
primary
NPC
cultures
derived
hippocampus
newborn
used,
which
led
locomotor
increased
stress,
particularly
cortex,
indicated
elevated
MDA
levels
GSH
levels.
reversed
these
effects,
notably
restoring
reducing
carbonylation
cerebellum.
Chronic
improved
markers
MDA,
SOD,
CAT,
GST.
Furthermore,
exhibits
properties
alleviating
motor
dysfunction,
suggesting
therapeutic
agent
neuroinflammatory
disorders.
However,
did
not
affect
cell
proliferation,
indicating
that
this
cardiotonic
steroid
alter
cycle
cells.
Язык: Английский