Research Square (Research Square),
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 7, 2025
Abstract
The
increasing
prevalence
of
obesity-driven
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
urges
the
development
new
therapeutic
strategies.
Totum-448
is
a
unique
patented
combination
polyphenol-rich
plant
extracts
designed
to
reduce
hepatic
steatosis,
risk
factor
for
steatohepatitis
and
type
2
diabetes.
In
this
study,
we
investigated
effects
on
homeostasis
in
diet-induced
MASLD
mice.
For
purpose,
male
C57Bl6/J
mice
were
fed
high-fat
diet
with
sucrose-containing
drinking
water
12
weeks,
followed
by
supplementation
or
without
4
weeks.
Body
weight/composition,
caloric
intake,
plasma
parameters
whole-body
glucose
tolerance
measured
throughout
study
fecal
microbiota
composition
was
determined
16S
sequencing.
Hepatic
transcriptomic/lipidomic
profiles
immune
cell
assessed
histological/biochemical
assays,
RNA
sequencing,
MS-based
lipidomics,
spectral
flow
cytometry.
We
found
that
significantly
lowered
hyperinsulinemia
systemic
intolerance
affecting
body
weight,
fat
mass,
calorie
feces
production
composition.
Furthermore,
decrease
activity
score
macrovesicular
triglycerides
cholesterol
contents,
alanine
aminotransferase
levels
observed.
also
reduced
inflammatory
pro-fibrotic
transcriptomic
signatures
decreased
both
MASLD-induced
loss
tissue-resident
Kupffer
cells
recruitment
monocyte-derived
pro-inflammatory
macrophages.
Altogether,
reduces
steatosis
inflammation
insulin-resistant,
steatotic,
obese
mice,
dual
effect
likely
contributes
improved
homeostasis.
Supplementation
may
therefore
constitute
promising
novel
nutritional
approach
patients.
Pharmacological Reviews,
Journal Year:
2024,
Volume and Issue:
76(3), P. 454 - 499
Published: Jan. 30, 2024
Steatotic
liver
disease
(SLD)
displays
a
dynamic
and
complex
phenotype.
Consequently,
the
metabolic
dysfunction-associated
steatotic
(MASLD)/metabolic
steatohepatitis
(MASH)
therapeutic
pipeline
is
expanding
rapidly
in
multiple
directions.
In
parallel,
non-invasive
tools
for
diagnosing
monitoring
responses
to
interventions
are
being
studied,
clinically
feasible
findings
explored
as
primary
outcomes
interventional
trials.
The
realization
that
distinct
subgroups
exist
under
umbrella
of
SLD
should
guide
more
precise
personalized
treatment
recommendations
facilitate
advancements
pharmacotherapeutics.
This
review
summarizes
recent
updates
pathophysiology-based
nomenclature
outlines
both
effective
pharmacotherapeutics
those
MASLD/MASH,
detailing
their
mode
action
current
status
phase
2
3
clinical
Of
extensive
arsenal
MASLD/MASH
pipeline,
several
have
been
rejected,
whereas
other,
mainly
monotherapy
options,
shown
only
marginal
benefits
now
tested
part
combination
therapies,
yet
others
still
development
monotherapies.
Although
successful
drug
candidate
(or
combinations)
remains
elusive,
such
approaches
will
ideally
target
MASH
fibrosis
while
improving
cardiometabolic
risk
factors.
Due
urgent
need
novel
strategies
potential
availability
safety
tolerability
data,
repurposing
existing
approved
drugs
an
appealing
option.
Finally,
it
essential
highlight
and,
by
extension,
MASLD
be
recognized
approached
systemic
affecting
organs,
with
vigorous
implementation
interdisciplinary
coordinated
plans.
Significance
Statement
SLD,
including,
among
others,
MASH,
considered
most
prevalent
chronic
condition
than
one-fourth
global
population.
aims
provide
information
regarding
pathophysiology,
diagnosis,
management
line
guidelines
Collectively,
hoped
provided
furthers
understanding
state
direct
implications
stimulates
additional
research
initiatives.
Food Science & Nutrition,
Journal Year:
2024,
Volume and Issue:
12(5), P. 3097 - 3111
Published: Feb. 16, 2024
Abstract
Liver
diseases,
encompassing
conditions
such
as
cirrhosis,
present
a
substantial
global
health
challenge
with
diverse
etiologies,
including
viral
infections,
alcohol
consumption,
and
non‐alcoholic
fatty
liver
disease
(NAFLD).
The
exploration
of
natural
compounds
therapeutic
agents
has
gained
traction,
notably
the
herbal
remedy
milk
thistle
(
Silybum
marianum
),
its
active
extract,
silymarin,
demonstrating
remarkable
antioxidant
hepatoprotective
properties
in
extensive
preclinical
investigations.
It
can
protect
healthy
cells
or
those
that
have
not
yet
sustained
permanent
damage
by
reducing
oxidative
stress
mitigating
cytotoxicity.
Silymarin,
compound
properties,
anti‐inflammatory
effects,
antifibrotic
activity,
shown
potential
treating
caused
alcohol,
NAFLD,
drug‐induced
toxicity,
hepatitis.
Legalon®
is
top‐rated
medication
excellent
oral
bioavailability,
effective
absorption,
effectiveness.
Its
component,
Eurosil
85®
also,
commercial
product,
lipophilic
enhanced
special
formulation
processes.
during
clinical
trials,
shows
improvements
function,
reduced
mortality
rates,
alleviation
symptoms
across
various
disorders,
safety
assessments
showing
low
adverse
effects.
Overall,
silymarin
emerges
promising
multifaceted
diseases.
Medicina,
Journal Year:
2023,
Volume and Issue:
59(6), P. 1136 - 1136
Published: June 12, 2023
Type
2
Diabetes
Mellitus
(T2DM)
and
non-alcoholic
fatty
liver
disease
(NAFLD)
are
part
of
metabolic
syndrome
share
multiple
causal
associations.
Both
conditions
have
an
alarmingly
increasing
incidence
lead
to
complications,
which
impact
on
a
variety
organs
systems,
such
as
the
kidneys,
eyes,
nervous
cardiovascular
or
may
cause
disruptions.
Sodium-glucose
cotransporter
2-inhibitors
(SGLT2-i),
antidiabetic
class
with
well-established
benefits,
its
members
also
been
studied
for
their
presumed
effects
steatosis
fibrosis
improvement
in
patients
NAFLD
steatohepatitis
(NASH).
The
MEDLINE
Cochrane
databases
were
searched
randomized
controlled
trials
examining
efficacy
SGLT2-i
treatment
NAFLD/NASH
T2DM.
Of
originally
identified
179
articles,
21
articles
included
final
data
analysis.
Dapagliflozin,
empagliflozin,
canagliflozin
some
most
used
agents
proven
treating
by
addressing/targeting
different
pathophysiological
targets/mechanisms:
insulin
sensitivity
improvement,
weight
loss,
especially
visceral
fat
glucotoxicity,
lipotoxicity
even
chronic
inflammation.
Despite
considerable
variability
study
duration,
sample
size,
diagnostic
method,
resulted
improvements
non-invasive
markers
This
systematic
review
offers
encouraging
results
that
place
at
top
therapeutic
arsenal
diagnosed
T2DM
NAFLD/NASH.
Frontiers in Medicine,
Journal Year:
2023,
Volume and Issue:
10
Published: Nov. 27, 2023
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD),
formerly
defined
as
non-alcoholic
fatty
(NAFLD),
is
a
disorder
marked
by
the
excessive
deposition
of
lipids
in
liver,
giving
rise
to
spectrum
pathologies
encompassing
steatohepatitis,
fibrosis/cirrhosis,
and
hepatocellular
carcinoma.
Despite
alarming
increase
its
prevalence,
US
Food
Drug
Administration
has
yet
approve
effective
pharmacological
therapeutics
for
clinical
use.
MASLD
characterized
accretion
within
hepatic
system,
arising
from
disarray
lipid
provision
(whether
through
absorption
circulating
or
de
novo
lipogenesis)
elimination
(via
free
acid
oxidation
secretion
triglyceride-rich
lipoproteins).
This
leads
accumulation
lipotoxic
substances,
cellular
pressure,
damage,
fibrosis.
Indeed,
regulation
metabolism
pathway
intricate
multifaceted,
involving
myriad
factors,
such
membrane
transport
proteins,
metabolic
enzymes,
transcription
factors.
Here,
we
will
review
existing
literature
on
key
process
understand
latest
progress
this
molecular
mechanism.
Notably,
lipogenesis
roles
two
main
factors
other
enzymes
are
highlighted.
Furthermore,
delve
into
realm
drug
research,
examining
recent
made
understanding
MASLD.
Additionally,
outline
prospective
avenues
future
research
based
our
unique
perspectives.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(4), P. 826 - 826
Published: April 9, 2024
Non-alcoholic
fatty
liver
disease
(NAFLD)
is
a
major
public
health
issue
worldwide.
It
the
most
common
in
Western
countries,
andits
global
prevalence
estimated
to
be
up
35%.
However,
its
diagnosis
may
elusive,
because
biopsy
relatively
rarely
performed
and
usually
only
advanced
stages
of
disease.
Therefore,
several
non-invasive
scores
applied
more
easily
diagnose
monitor
NAFLD.
In
this
review,
we
discuss
various
biomarkers
imaging
that
could
useful
diagnosing
managing
Despite
fact
general
measures,
such
as
abstinence
from
alcohol
modulation
other
cardiovascular
risk
factors,
should
applied,
mainstay
prevention
management
weight
loss.
Bariatric
surgery
suggested
means
confront
addition,
pharmacological
treatment
with
GLP-1
analogues
or
GIP
agonist
tirzepatide
advisable.
focus
on
utility
agonists
lowering
body
weight,
their
pharmaceutical
potential,
safety
profile,
already
evidenced
inanimal
human
studies.
We
also
elaborate
options,
use
vitamin
E,
probiotics,
especially
next-generation
prebiotics
context.
Finally,
explore
future
perspectives
regarding
administration
analogues,
agonists,
probiotics/prebiotics
prevent
combat
The
newest
drugs
pegozafermin
resmetiron,
which
seem
very
promising,
arealso
discussed.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(7), P. 3746 - 3746
Published: March 27, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
is
influenced
by
a
variety
of
factors,
including
environmental
and
genetic
factors.
The
most
significant
outcome
the
alteration
free
fatty
acid
triglyceride
metabolism.
Lipotoxicity,
impaired
autophagy,
chronic
inflammation,
oxidative
stress,
as
well
coexisting
insulin
resistance,
obesity,
changes
in
composition
gut
microbiota,
are
also
considered
crucial
factors
pathogenesis
MASLD.
Resveratrol
polyphenolic
compound
that
belongs
to
stilbene
subgroup.
This
review
summarises
available
information
on
therapeutic
effects
resveratrol
against
has
demonstrated
promising
antisteatotic,
antioxidant,
anti-inflammatory
activities
cells
vitro
animal
studies.
been
associated
with
inhibiting
NF-κB
pathway,
activating
SIRT-1
AMPK
pathways,
normalizing
intestinal
microbiome,
alleviating
inflammation.
However,
clinical
studies
have
yielded
inconclusive
results
regarding
efficacy
hepatic
steatosis
or
reducing
any
parameters
found
MASLD
human
patients.
lack
homogeneity
between
studies,
low
bioavailability
resveratrol,
population
variability
when
compared
models
could
be
reasons
for
this.
Frontiers in Nutrition,
Journal Year:
2024,
Volume and Issue:
11
Published: March 19, 2024
The
definition
of
“Metabolic
Associated
Fatty
Liver
Disease
–
MAFLD”
has
replaced
the
previous
Nonalcoholic
(NAFLD),
because
cardiometabolic
criteria
have
been
added
for
prevention
cardiological
risk
in
these
patients.
This
leads
to
an
in-depth
study
bidirectional
relationships
between
hepatic
steatosis,
Type
2
Diabetes
Mellitus
(T2DM),
Cardiovascular
(CVD)
and/or
their
complications.
Lifestyle
modification,
which
includes
correct
nutrition
combined
with
regular
physical
activity,
represents
therapeutic
cornerstone
MAFLD.
When
therapy
is
required,
there
not
clear
accord
on
how
proceed
optimal
way
nutraceutical
or
pharmacological
therapy.
Numerous
studies
attempted
identify
nutraceuticals
a
significant
benefit
metabolic
alterations
and
contribute
improvement
steatosis.
Several
evidences
are
supporting
use
silymarin,
berberine,
curcumin,
Nigella
sativa
,
Ascophyllum
nodosum
Fucus
vesiculosus
vitamin
E,
coenzyme
Q10
Omega-3.
However,
more
evidence
regarding
long-term
efficacy
safety
compounds
required.
There
numerous
that
highlights
therapies
such
as
incretins
Proprotein
Convertase
Subtilisin/Kexin
type
9
(PCSK9)
inhibitors
other
similar
which,
by
assisting
existing
pathologies
diabetes,
hypertension,
insulin
resistance,
given
breakthrough
reduction
risk.
review
gave
overview
current
strategies
expected
aid
treatment
