Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Дек. 5, 2024
The
potential
of
natural
phytochemicals
in
mitigating
depression
has
been
supported
by
substantial
evidence.
This
study
evaluated
a
total
88
with
antidepressant
properties
targeting
serotonin
(5-HT)
receptors
(5-HT1A,
5-HT4,
and
5-HT7)
using
molecular
docking,
ADMET
(Absorption,
Distribution,
Metabolism,
Excretion,
Toxicity)
analysis,
internal
coordinates
normal
mode
analysis
(NMA),
dynamics
simulation
(MDS),
free
energy
calculation.
Five
compounds
(Genistein,
Kaempferol,
Daidzein,
Peonidin,
glycitein)
exhibited
favorable
pharmacokinetic
improved
binding
scores,
indicating
their
as
effective
antidepressants.
Redocking
superimposition
5-HT
cocrystal
structures
validated
these
findings.
Furthermore,
NMA,
MDS,
calculations
confirmed
the
stability
deformability
ligand-receptor
complexes,
suggesting
that
can
effectively
interact
to
modulate
depressive
symptoms.
These
powerful
phytochemicals,
abundantly
found
soybeans,
fruits,
vegetables,
herbs,
represent
promising
avenue
for
developing
treatments
depression.
Further
vitro
vivo
studies
are
warranted
explore
efficacy
alleviating
stress
through
interactions
receptors.
Frontiers in Pharmacology,
Год журнала:
2023,
Номер
14
Опубликована: Окт. 2, 2023
Chronic
pain
and
depression
are
highly
prevalent
pathologies
cause
a
major
socioeconomic
burden
to
society.
affects
the
emotional
state
of
individuals
suffering
from
it,
while
worsens
prognosis
chronic
patients
may
diminish
effectiveness
treatments.
There
is
high
comorbidity
rate
between
both
pathologies,
which
might
share
overlapping
mechanisms.
This
review
explores
evidence
pinpointing
role
for
ventral
tegmental
area
(VTA)
as
hub
where
processing
converge.
In
addition,
feasibility
using
VTA
possible
therapeutic
target
discussed.
The
VTA,
dopaminergic
system
in
general,
studied
mood
disorders,
especially
deficits
reward-processing
motivation.
Conversely,
less
regarded
it
concerns
study
central
mechanisms
its
mood-associated
consequences.
Here,
we
first
outline
brain
circuits
involving
focusing
on
often-understudied
VTA.
Next,
highlight
state-of-the-art
findings
supporting
emergence
link
pathways
Thus,
envision
promising
part
putative
innovative
approaches
treat
effects
mood.
Finally,
emphasize
urge
develop
use
animal
models
depression-like
symptoms
considered
conjunction.
Phytotherapy Research,
Год журнала:
2023,
Номер
38(1), С. 231 - 240
Опубликована: Окт. 19, 2023
Abstract
To
explore
the
antidepressant
effects
and
targets
of
atractylenolide
I
(ATR)
through
a
network
pharmacological
approach.
Relevant
ATR
depression
analyzed
by
pharmacology
were
scored
(identifying
5‐HT2A
targets).
Through
elevated
plus
maze,
open
field,
tail
suspension,
forced
swimming
tests,
behavioral
changes
mice
with
(chronic
unpredictable
mild
stress
[CUMS])
examined,
levels
neurotransmitters
including
serotonin,
dopamine,
norepinephrine
(5‐HT,
DA,
NE)
determined.
The
binding
to
was
verified
small
molecular‐protein
docking.
improved
behaviors
CUMS
mice,
their
5‐HT,
NE,
exerted
protective
effect
on
nerve
cell
injury.
After
knockout,
failed
further
improve
behaviors.
According
results
docking
analysis,
acted
as
an
inhibitor
5‐HT2A.
can
modulate
targeting
IEEE Transactions on Medical Robotics and Bionics,
Год журнала:
2024,
Номер
6(2), С. 674 - 684
Опубликована: Март 25, 2024
Deep
brain
stimulation
(DBS)
has
demonstrated
therapeutic
efficacy
in
the
treatment
of
neurological
and
psychiatric
disorders.
Currently,
DBS
devices
employ
an
openloop
configuration,
requiring
manual
adjustment
electrical
to
address
patient
needs.
For
this
reason,
closed-loop
is
being
developed,
delivering
appropriate
ondemand
based
on
internal
signal
monitoring.
A
key
challenge
current
research
complexity
interpreting
measured
signals
interventions,
currently
no
miniaturised
device
on-board
artificial
intelligence
(AI)
meet
need.
This
paper
presents
a
new
device,
named
SmartStim,
that
uses
AI
monitor
dynamically
changing
biomarkers.
In
addition,
decides
if
output
stimulator
required
for
treatment.
two
components:
hardware
module
(neural
sensor
unit,
processor,
neurostimulator)
software
(data
processing,
AI,
firmware).
The
neural
unit
comprised
subcomponents.
first
potentiostat
can
perform
impedance
analysis,
second
dedicated
fast
scan
cyclic
voltammetry
(FSCV)
front-end
rates
up
1000
V/s.
currentcontrolled
waveforms
frequency
range
5
Hz–200
Hz,
1
μA
10
mA,
with
active
charge
balancing.
Five
experiments
were
conducted
validate
SmartStim:
static
resistive
load
test,
emulated
resistance
electrochemical
cell
dynamic
serotonin
test.
These
confirm
potential
SmartStim
identify
neurochemical
patterns
mouse
using
AI.
Medicinal Research Reviews,
Год журнала:
2024,
Номер
44(6), С. 2640 - 2706
Опубликована: Май 29, 2024
5-HT1A
receptor
(5-HT1A-R)
is
a
serotoninergic
G-protein
coupled
subtype
which
contributes
to
several
physiological
processes
in
both
central
nervous
system
and
periphery.
Despite
being
the
first
5-HT-R
identified,
cloned
studied,
it
still
represents
very
attractive
target
drug
discovery
continues
be
focus
of
myriad
campaigns
due
its
involvement
numerous
neuropsychiatric
disorders.
The
structure-activity
relationship
studies
(SAR)
performed
over
last
years
have
been
devoted
three
main
goals:
(i)
design
synthesis
5-HT1A-R
selective/preferential
ligands;
(ii)
identification
biased
agonists,
differentiating
pre-
versus
post-synaptic
agonism
signaling
cellular
mechanisms;
(iii)
development
multitarget
compounds
endowed
with
well-defined
poly-pharmacological
profiles
targeting
along
other
serotonin
receptors,
transporter
(SERT),
D2-like
receptors
and/or
enzymes,
such
as
acetylcholinesterase
phosphodiesterase,
promising
strategy
for
management
complex
psychiatric
neurodegenerative
In
this
review,
medicinal
chemistry
aspects
ligands
acting
or
agonists
antagonists
belonging
different
chemotypes
developed
7
(2017-2023)
discussed.
chemical
pharmacological
tools
molecular
imaging
also
described.
Finally,
interest
therapeutic
potential
considered.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(20), С. 11276 - 11276
Опубликована: Окт. 20, 2024
We
describe
the
design,
synthesis
and
structure–activity
relationship
of
a
novel
series
1-(4-(7-azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1H-indol-3-yl)pyrrolidine-2,5-dione
derivatives
with
combined
effects
on
serotonin
(5-HT1A)
dopamine
(D2)
receptors
(5-HT),
noradrenaline
(NA),
(DA)
transporters
as
multi-target
directed
ligands
for
treatment
depression.
All
tested
compounds
demonstrated
good
affinity
transporter
(SERT).
Among
them,
11
4
emerged
lead
candidates
because
their
promising
pharmacological
profile
based
in
vitro
studies.
Compound
displayed
high
5-HT1A
(Ki
=
128.0
nM)
D2
51.0
receptors,
SERT
9.2
DAT
288.0
transporters,
whereas
compound
exhibited
most
desirable
binding
to
SERT/NET/DAT
among
series:
Ki
47.0
nM/167.0
nM/43%
inhibition
at
1
µM.
These
results
suggest
that
represent
templates
future
development
antidepressant
drugs.
Current Pharmaceutical Design,
Год журнала:
2023,
Номер
30(3), С. 180 - 214
Опубликована: Дек. 28, 2023
Introduction:
This
narrative
review
addresses
the
clinical
challenges
in
stress-related
disorders
such
as
depression,
focusing
on
interplay
between
neuron-specific
and
pro-inflammatory
mechanisms
at
cellular,
cerebral,
systemic
levels.
Objective:
We
aim
to
elucidate
molecular
linking
chronic
psychological
stress
with
low-grade
neuroinflammation
key
brain
regions,
particularly
roles
of
G
proteins
serotonin
(5-HT)
receptors.
Methods:
comprehensive
literature
employs
systematic,
narrative,
scoping
methodologies,
combined
approaches
general
pathology.
It
synthesizes
current
research
shared
signaling
pathways
involved
responses
neuroinflammation,
including
calcium-dependent
mechanisms,
mitogen-activated
protein
kinases,
transcription
factors
like
NF-κB
p53.
The
also
focuses
role
protein-coupled
neurotransmitter
receptors
(GPCRs)
immune
responses,
a
detailed
analysis
how
13
14
types
human
5-HT
contribute
depression
neuroinflammation.
Results:
reveals
complex
interaction
signals
immunoinflammatory
pathologies.
highlights
GPCRs
canonical
inflammatory
mediators
influencing
both
pathological
physiological
processes
nervous
tissue.
Conclusion:
proposed
Neuroimmunoinflammatory
Stress
Model
(NIIS
Model)
suggests
that
proinflammatory
pathways,
mediated
by
metabotropic
ionotropic
receptors,
are
crucial
for
maintaining
neuronal
homeostasis.
Chronic
mental
can
disrupt
this
balance,
leading
increased
states
contributing
neuropsychiatric
psychosomatic
disorders,
depression.
model
integrates
traditional
theories
pathogenesis,
offering
understanding
multifaceted
nature
condition.
Frontiers in Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Март 4, 2024
Neurodegenerative
diseases
refer
to
a
battery
of
medical
conditions
that
affect
the
survival
and
function
neurons
in
brain,
which
are
mainly
presented
with
progressive
loss
cognitive
and/or
motor
function.
Acupuncture
showed
benign
effects
improving
neurological
deficits,
especially
on
movement
impairment.
Here,
we
reviewed
therapeutic
mechanisms
acupuncture
at
neural
circuit
level
cognition
disorders,
summarizing
influence
dopaminergic
system,
glutamatergic
γ-amino
butyric
acid-ergic
(GABAergic)
serotonergic
cholinergic
glial
cells
synaptic
levels.
These
findings
can
provide
targets
for
clinical
treatment
perspectives
further
studies.
Regenerative medicine reports .,
Год журнала:
2024,
Номер
1(2), С. 222 - 231
Опубликована: Дек. 1, 2024
Nicotine
withdrawal
precipitates
anxiety-
and
depression-like
behaviors
associated
with
disruptions
in
neurotransmitter
systems,
alterations
glial
neurotrophic
factors,
heightened
oxidative
stress.
This
study
aimed
to
investigate
the
potential
therapeutic
effects
of
magnesium
sulfate
(MgSO₄)
on
nicotine
withdrawal-induced
anxiety
depression
rats
as
well
its
implications
for
regenerative
psychiatry.
These
findings
indicated
that
MgSO₄
administration
effectively
attenuated
induced
by
rat
model.
The
beneficial
were
accompanied
modulation
cortical
serotonin
metabolism,
a
reduction
monoamine
oxidase
A
activity,
upregulation
brain-derived
factor,
downregulation
fibrillary
acidic
protein,
amelioration
stress
behaviors.
Therefore,
can
ameliorate
detrimental
at
cellular
behavioral
levels
has
certain
psychiatry,
paving
way
application
substance
abuse-related
diseases.
