The eukaryotic elongation factor 2 kinase inhibitor, A484954, induces hypoglycaemic and hypotensive effects
British Journal of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 22, 2025
Background
and
Purpose
Eukaryotic
elongation
factor
2
kinase
(eEF2K)
belongs
to
the
Ca
2+
/calmodulin‐dependent
protein
family.
We
previously
revealed
that
A484954,
a
selective
eEF2K
inhibitor,
caused
hypotensive
diuretic
effects
via
production
of
nitric
oxide
(NO)
in
spontaneously
hypertensive
rats.
Otsuka
Long–Evans
Tokushima
Fatty
(OLETF)
rats
are
because
obesity
type
diabetes.
Because
an
NO
synthase
inhibitor
was
reported
increase
expression
sodium
glucose
co‐transporter
(SGLT2),
we
hypothesised
A484954
causes
not
only
but
also
hypoglycaemic
OLETF
Experimental
Approach
To
test
hypothesis,
examined
administration
on
hyperglycaemia
hypertension
were
given
intraperitoneal
injection
(2.5
mg
kg
−1
day
)
for
7
days.
Then,
measured
blood
urinary
level,
urine
output,
systolic
pressure
ventricular
contractility.
conducted
Western
blotting
isometric
tension
measurements.
Key
Results
induced
decrease
glucose,
excretion,
kidney
SGLT2.
In
addition,
pressure,
NO‐dependent
vasorelaxation,
effect.
Further,
enhanced
left
Conclusion
Implications
We,
first
time,
(1)
through
increasing
excretion
decreasing
SGLT2,
(2)
improved
diabetic
complication,
including
hypertension,
vasorelaxation
diuresis
production,
(3)
had
positive
inotropic
Язык: Английский
Black Seed Oil Boosts Antidiabetic Activity of Glibenclamide: Development of Solidified Self Nanoemulsifying Drug Delivery System and Evaluation in Streptozotocin-Induced Diabetic Rat Model
Pharmaceutical Development and Technology,
Год журнала:
2025,
Номер
unknown, С. 1 - 17
Опубликована: Апрель 3, 2025
Self
nano-emulsifying
drug
delivery
system
(SNEDDS)
has
been
widely
used
to
enhance
dissolution
and
bioavailability
of
glibenclamide
(GB).
In
addition,
black
seed
oil,
containing
bioactive
thymoquinone
(TQ),
showed
promising
antihyperglycemic
effect.
Therefore,
this
work
aims
design
solid
SNEDDS
formulation
composed
Black
oil
loaded
with
GB
its
activity.
Different
formulations
were
prepared
characterized
for
miscibility,
dispersibility,
droplet
size,
zeta
potential,
in-vitro
dissolution.
Moreover,
antidiabetic
activity
against
pure
was
evaluated
using
streptozotocin-induced
diabetic
rat
model.
The
selected
liquid
(F7)
consisted
Kolliphor
EL:
Caproyl
90:
BSO
that
produced
nanoemulsion
particles
(24.9
±
0.2nm).
solidified
from
F7,
the
(S4)
as
optimum
TQ
had
a
DE%
value
73.16
0.59
70.9%,
respectively.
Overall,
both
GB-SNEDDS
significantly
reduced
blood
glucose
levels
compared
control
group.
showing
superior
efficacy
(67%
reduction,
p
=
5.5
×
10-5)
(52%
1.5
10-4).
GB-SNEDD
significant
(p
0.0363)
reducing
action
on
Present
results
boosted
oral
hypoglycemic
drugs.
This
could
open
new
avenues
natural
agent
while
preparing
formulation.
Язык: Английский