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Downregulation of hepatic fat accumulation, inflammation and fibrosis by nerolidol in purpose built western-diet-induced multiple-hit pathogenesis of NASH animal model.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
June 1, 2022
Usman Sabir et al. (7 authors)
Journal ArticleAnimal Study
Study Details

Study Goal

The researchers aimed to evaluate the impact of a Western Diet on NASH development and assess the anti-NASH effects of nerolidol in a rat model.

Results Summary

The Western Diet induced insulin resistance, hepatic steatosis, dyslipidemia, and elevated liver enzymes in rats. Nerolidol treatment reduced steatosis, inflammation, and oxidative stress, demonstrating anti-fibrotic effects.

Population

Rat model fed a hypercaloric Western Diet.

Effective Dosage

250 and 500 mg/kg of nerolidol.

Duration

Not specified in the abstract.

Interactions

None mentioned.

Extracted Claims (17)
InterventionDirectionEndpointPopulationDosageImpactClaim #
Western diet style (fast food)
increase
nonalcoholic steatohepatitis (NASH)
-
-
is a primary etiological determinant for developing
#1
purpose-built diet
increase
insulin resistance
rat model
-
substantially induced
#2
purpose-built diet
increase
hepatic steatosis
rat model
-
substantially induced
#3
purpose-built diet
increase
dyslipidemia
rat model
-
substantially induced
#4
purpose-built diet
increase
elevation of liver enzymes
rat model
-
substantially induced
#5
purpose-built diet
increase
liver oxidative stress markers
disease control rats
-
increased
#6
purpose-built diet
increase
nitrites (NO2-)
disease control rats
-
increased
#7
purpose-built diet
increase
serum pro-inflammatory cytokine (TNF-α)
disease control rats
-
increased
#8
purpose-built diet
increase
hepatic collagen
disease control rats
-
increased
#9
Nerolidol oral treatment (250 and 500 mg/kg)
decrease
steatosis (macrovesicular and microvesicular)
-
-
substantially reduced
#10
Nerolidol oral treatment (250 and 500 mg/kg)
decrease
degeneration of hepatocytes
-
-
substantially reduced
#11
Nerolidol oral treatment (250 and 500 mg/kg)
decrease
inflammatory cells infiltration
-
-
substantially reduced
#12
Nerolidol (500 mg/kg dose)
decrease
circulatory TNF-α
-
-
reduced
#13
Nerolidol (500 mg/kg dose)
decrease
tissue collagen
-
-
reduced
#14
Nerolidol (500 mg/kg dose)
decrease
anti-fibrotic effect
-
-
expressing its
#15
Nerolidol treatment
decrease
hepatic lipid accumulation
-
-
significantly reduced
#16
Nerolidol treatment
decrease
disease progression
-
-
halted
#17
Abstract

Western diet style (fast food), which includes fatty frozen junk food, lard, processed meats, whole-fat dairy foods, cream, mayonnaise, butter, snacks, and fructose, is a primary etiological determinant for developing nonalcoholic steatohepatitis (NASH) worldwide. Here the primary focus is to see the impact of naturally identified essential oil on disease mechanisms developed in an animal model using the same ingredients. Currently, symptomatic therapies are recommended for the management of NASH due to non-availability of specific treatments. Therefore, the present study was designed to evaluate the potential anti-NASH effect of nerolidol in a rat model fed with a purpose-built diet. The diet substantially induced insulin resistance, hepatic steatosis, dyslipidemia, and elevation of liver enzymes in the experimental animals. The levels of liver oxidative stress markers, nitrites (NO2-), serum pro-inflammatory cytokine (TNF-α) and hepatic collagen were increased in disease control rats. Nerolidol oral treatment in ascending dose order of 250 and 500 mg/kg substantially reduced the steatosis (macrovesicular and microvesicular), degeneration of hepatocytes, and inflammatory cells infiltration. The amounts of circulatory TNF-α and tissue collagen were also reduced at 500 mg/kg dose of nerolidol, expressing its anti-fibrotic effect. The current study described the multiple-hit pathophysiology of NASH as enhanced steatosis, pro-inflammatory markers, and oxidative stress in rats, which resulted in the development of vicious insulin resistance. Nerolidol treatment significantly reduced hepatic lipid accumulation and halted disease progression induced by a hypercaloric diet.

Medical Subject Headings (MeSH)
AnimalsDiet, High-FatDiet, WesternDisease Models, AnimalDown-RegulationInflammationInsulin ResistanceLiverLiver CirrhosisMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseRatsSesquiterpenesTumor Necrosis Factor-alpha
Study Links
Quality Scores
Safety20
Efficacy85/10
Quality75/10
Citation Metrics
Total Citations13
Citations/Year4.3
Relative Citation Ratio1.77
NIH Percentile70.7%
Research Impact Scores
APT Score0.50
Weight Score1.29
Normalized Score0.57
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