<i>Calluna vulgaris</i> Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl<sub>4</sub> Administration

Fatty liver (FL) is one of the most prevalent diseases in the world, characterized by insulin resistance and hyperlipidemia, which consequently lead to neurodegenerative disorders through the induction of oxidative stress-inflammatory axis, which alters the neurotransmitters’ levels. <i>Callun...

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Main Author: Muhanad Alhujaily
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Separations
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Online Access:https://www.mdpi.com/2297-8739/10/2/94
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author Muhanad Alhujaily
author_facet Muhanad Alhujaily
author_sort Muhanad Alhujaily
collection DOAJ
description Fatty liver (FL) is one of the most prevalent diseases in the world, characterized by insulin resistance and hyperlipidemia, which consequently lead to neurodegenerative disorders through the induction of oxidative stress-inflammatory axis, which alters the neurotransmitters’ levels. <i>Calluna vulgaris</i> (CV)<i>,</i> also known as heather, has anti-inflammatory and antidepressant properties, making it a promising candidate for treating steatosis and brain lesions. This study aimed to assess the prophylactic and therapeutic effect of CV extract on brain dysfunction associated with steatosis. FL was induced in rats by CCl<sub>4</sub> oral administration (50 µL/Kg in olive oil three times/week) for six weeks. The protection group received 200 mg/kg CV extract orally for two weeks before and two weeks during FL induction, while the treatment group was orally administered CV extract after FL induction for one month. The biochemical parameters revealed that CCl<sub>4</sub> administration induced hepatotoxicity as blood-liver function parameters (AST, ALT, ALP, protein, and LDH) were increased by 1.8, 1.4, 2, 2.4, and 1.2-fold, respectively. Moreover, insulin resistance was characterized by a two-fold increase in the glucose, insulin, and lipid profile when compared to control one, at <i>p</i> < 0.05. Steatosis liver demonstrated a two-fold increase in all following parameters— acetaldehyde (AC), prooxidant (TBARS), acetylcholine esterase (AChE), monoamine oxidase (MAO), hyaluronidase, and ATPase—when compared to control one, at <i>p</i> < 0.05. CCl<sub>4</sub> administration led to brain lesions where the brain level of TBARS, insulin, cholesterol, AChE, and MAO was progressively increased by 2, 1.6, 2.2, 4, and 1.6-fold, respectively, that was associated with reduced glucose (8-fold) and GSH (2-fold) than that of control level, at <i>p</i> < 0.05. CV extract as a prophylactic and therapeutic agent increased GSH and decreased TBARS of both the liver and brain than that of induced group, at <i>p</i> < 0.05, normalized the activities of AChE and MAO, and increased insulin sensitivity where they successfully decreased the HOMA-IR, glucose, TG, and cholesterol compared to than that of induced group, at <i>p</i> < 0.05. This positive effect of CV extract contributed to the presence of polyphenolic compounds such as catechins (5.501 ± 0.056 µg/g extract), gallic (3.525 ± 0.143 µg/g) extract, and protocatechuic acid (2.719 ± 0.132 µg/g extract). Therefore, we concluded that FL induced brain dysfunction through the formation of ROS and elevation of insulin and lipid inside the brain tissue, which alter the amount of neurotransmitter and cellular energy production. Rich in polyphenolic compounds, CV extract functions as an antioxidant, antidiabetic, hepatoprotective, inhibitor of neurotransmitter catabolizing enzymes, and a regulator for energy production. Therefore, it can be used as a preventative or treatment for NAFLD and brain damage.
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spelling doaj.art-33c970aa3df74308ac424b8629e964812023-11-16T23:14:16ZengMDPI AGSeparations2297-87392023-01-011029410.3390/separations10020094<i>Calluna vulgaris</i> Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl<sub>4</sub> AdministrationMuhanad Alhujaily0Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 67714, Saudi ArabiaFatty liver (FL) is one of the most prevalent diseases in the world, characterized by insulin resistance and hyperlipidemia, which consequently lead to neurodegenerative disorders through the induction of oxidative stress-inflammatory axis, which alters the neurotransmitters’ levels. <i>Calluna vulgaris</i> (CV)<i>,</i> also known as heather, has anti-inflammatory and antidepressant properties, making it a promising candidate for treating steatosis and brain lesions. This study aimed to assess the prophylactic and therapeutic effect of CV extract on brain dysfunction associated with steatosis. FL was induced in rats by CCl<sub>4</sub> oral administration (50 µL/Kg in olive oil three times/week) for six weeks. The protection group received 200 mg/kg CV extract orally for two weeks before and two weeks during FL induction, while the treatment group was orally administered CV extract after FL induction for one month. The biochemical parameters revealed that CCl<sub>4</sub> administration induced hepatotoxicity as blood-liver function parameters (AST, ALT, ALP, protein, and LDH) were increased by 1.8, 1.4, 2, 2.4, and 1.2-fold, respectively. Moreover, insulin resistance was characterized by a two-fold increase in the glucose, insulin, and lipid profile when compared to control one, at <i>p</i> < 0.05. Steatosis liver demonstrated a two-fold increase in all following parameters— acetaldehyde (AC), prooxidant (TBARS), acetylcholine esterase (AChE), monoamine oxidase (MAO), hyaluronidase, and ATPase—when compared to control one, at <i>p</i> < 0.05. CCl<sub>4</sub> administration led to brain lesions where the brain level of TBARS, insulin, cholesterol, AChE, and MAO was progressively increased by 2, 1.6, 2.2, 4, and 1.6-fold, respectively, that was associated with reduced glucose (8-fold) and GSH (2-fold) than that of control level, at <i>p</i> < 0.05. CV extract as a prophylactic and therapeutic agent increased GSH and decreased TBARS of both the liver and brain than that of induced group, at <i>p</i> < 0.05, normalized the activities of AChE and MAO, and increased insulin sensitivity where they successfully decreased the HOMA-IR, glucose, TG, and cholesterol compared to than that of induced group, at <i>p</i> < 0.05. This positive effect of CV extract contributed to the presence of polyphenolic compounds such as catechins (5.501 ± 0.056 µg/g extract), gallic (3.525 ± 0.143 µg/g) extract, and protocatechuic acid (2.719 ± 0.132 µg/g extract). Therefore, we concluded that FL induced brain dysfunction through the formation of ROS and elevation of insulin and lipid inside the brain tissue, which alter the amount of neurotransmitter and cellular energy production. Rich in polyphenolic compounds, CV extract functions as an antioxidant, antidiabetic, hepatoprotective, inhibitor of neurotransmitter catabolizing enzymes, and a regulator for energy production. Therefore, it can be used as a preventative or treatment for NAFLD and brain damage.https://www.mdpi.com/2297-8739/10/2/94non-alcoholic fatty liver diseaseacetylcholinesterasemonoamine oxidaseHOMA-IRoxidative stress
spellingShingle Muhanad Alhujaily
<i>Calluna vulgaris</i> Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl<sub>4</sub> Administration
Separations
non-alcoholic fatty liver disease
acetylcholinesterase
monoamine oxidase
HOMA-IR
oxidative stress
title <i>Calluna vulgaris</i> Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl<sub>4</sub> Administration
title_full <i>Calluna vulgaris</i> Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl<sub>4</sub> Administration
title_fullStr <i>Calluna vulgaris</i> Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl<sub>4</sub> Administration
title_full_unstemmed <i>Calluna vulgaris</i> Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl<sub>4</sub> Administration
title_short <i>Calluna vulgaris</i> Crude Extract Reverses Liver Steatosis and Insulin Resistance-Associated-Brain Lesion Induced by CCl<sub>4</sub> Administration
title_sort i calluna vulgaris i crude extract reverses liver steatosis and insulin resistance associated brain lesion induced by ccl sub 4 sub administration
topic non-alcoholic fatty liver disease
acetylcholinesterase
monoamine oxidase
HOMA-IR
oxidative stress
url https://www.mdpi.com/2297-8739/10/2/94
work_keys_str_mv AT muhanadalhujaily icallunavulgarisicrudeextractreversesliversteatosisandinsulinresistanceassociatedbrainlesioninducedbycclsub4subadministration