The prophylactic treatment of Egyptian, Trigonella foenum - graecum L., Extract in comparison to pure diosgenin on experimentally induced non-alcoholic steatohepatitis: New targets via AMPK, RAR, and FXR pathways

Background: Non-alcoholic steatohepatitis (NASH) is an inflammatory liver condition that damages the liver by accumulating fat. Aim: Our study sought to explore the mechanisms involved through which fengreek, Trigonella foenum - graecum L., extract (FE) or diosgenin (DSG) exerted their hepatoprotect...

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Main Authors: Manar M. Eltamalawy, A.F. Abdel-Aziz, Tarek M. Mohamed, Naglaa F. Khedr
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Phytomedicine Plus
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2667031323000179
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author Manar M. Eltamalawy
A.F. Abdel-Aziz
Tarek M. Mohamed
Naglaa F. Khedr
author_facet Manar M. Eltamalawy
A.F. Abdel-Aziz
Tarek M. Mohamed
Naglaa F. Khedr
author_sort Manar M. Eltamalawy
collection DOAJ
description Background: Non-alcoholic steatohepatitis (NASH) is an inflammatory liver condition that damages the liver by accumulating fat. Aim: Our study sought to explore the mechanisms involved through which fengreek, Trigonella foenum - graecum L., extract (FE) or diosgenin (DSG) exerted their hepatoprotective activity in NASH-induced rat model. Methods: FE was prepared via a Soxhlet extraction, followed by acid hydrolysis. Sixty male albino rats were randomly distributed into six groups: normal control (NC) group, NASH-control group, FE group, low DSG dose (LD-1) group, medium DSG dose (MD-5) group, and high DSG dose (HD-10) group. The influence of both FE and pure DSG on serum liver indices, lipid profile, glucose, insulin, and Homeostasis model assessment (HOMA) of insulin resistance (IR) were determined. Liver histopathology, liver gene expression of adenosine monophosphate (AMP)-activated protein kinase (AMPK), Farnesoid X receptor (FXR) and retinoic acid receptor (RAR), and protein expression of phospho-acetyl CoA carboxylase (p-ACC) were evaluated. Results: A significant amelioration was noticed in serum liver indices, lipid profile, liver histopathology, body weight gain, and p-ACC/ACC protein expression in both FE and DSG treated groups compared to the NASH untreated group. DSG-treated groups significantly (p<0.05) decreased serum glucose levels and HOMA-IR compared to the NASH untreated group. FE significantly upregulated AMPK compared to the NASH untreated group and DSG-treated groups. However, RAR downregulation and FXR overexpression of the NASH group were not normalized in treated groups. Conclusion: This study proved that FE and DSG both protected the liver against NASH. The DSG impact was dose-dependent. However, the activation of the AMPK cascade was believed to be the mechanism by which FE exerted its hepatoprotective effects.
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spelling doaj.art-aadf16f2a32d4b0d816a9aab698dba2b2023-05-11T04:24:50ZengElsevierPhytomedicine Plus2667-03132023-05-0132100421The prophylactic treatment of Egyptian, Trigonella foenum - graecum L., Extract in comparison to pure diosgenin on experimentally induced non-alcoholic steatohepatitis: New targets via AMPK, RAR, and FXR pathwaysManar M. Eltamalawy0A.F. Abdel-Aziz1Tarek M. Mohamed2Naglaa F. Khedr3Biochemistry Unit, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Postal code: 35516, Egypt; Corresponding author.Biochemistry Unit, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Postal code: 35516, EgyptBiochemistry Unit, Chemistry Department, Faculty of Science, Tanta University, Tanta, Postal code: 31527, EgyptBiochemistry Department, Faculty of Pharmacy, Tanta University, Tanta, Postal code: 31527, EgyptBackground: Non-alcoholic steatohepatitis (NASH) is an inflammatory liver condition that damages the liver by accumulating fat. Aim: Our study sought to explore the mechanisms involved through which fengreek, Trigonella foenum - graecum L., extract (FE) or diosgenin (DSG) exerted their hepatoprotective activity in NASH-induced rat model. Methods: FE was prepared via a Soxhlet extraction, followed by acid hydrolysis. Sixty male albino rats were randomly distributed into six groups: normal control (NC) group, NASH-control group, FE group, low DSG dose (LD-1) group, medium DSG dose (MD-5) group, and high DSG dose (HD-10) group. The influence of both FE and pure DSG on serum liver indices, lipid profile, glucose, insulin, and Homeostasis model assessment (HOMA) of insulin resistance (IR) were determined. Liver histopathology, liver gene expression of adenosine monophosphate (AMP)-activated protein kinase (AMPK), Farnesoid X receptor (FXR) and retinoic acid receptor (RAR), and protein expression of phospho-acetyl CoA carboxylase (p-ACC) were evaluated. Results: A significant amelioration was noticed in serum liver indices, lipid profile, liver histopathology, body weight gain, and p-ACC/ACC protein expression in both FE and DSG treated groups compared to the NASH untreated group. DSG-treated groups significantly (p<0.05) decreased serum glucose levels and HOMA-IR compared to the NASH untreated group. FE significantly upregulated AMPK compared to the NASH untreated group and DSG-treated groups. However, RAR downregulation and FXR overexpression of the NASH group were not normalized in treated groups. Conclusion: This study proved that FE and DSG both protected the liver against NASH. The DSG impact was dose-dependent. However, the activation of the AMPK cascade was believed to be the mechanism by which FE exerted its hepatoprotective effects.http://www.sciencedirect.com/science/article/pii/S2667031323000179Acetyl-CoA carboxylaseDiosgeninFarnesoid X receptorFenugreekNon-alcoholic steatohepatitisRetinoic acid receptor
spellingShingle Manar M. Eltamalawy
A.F. Abdel-Aziz
Tarek M. Mohamed
Naglaa F. Khedr
The prophylactic treatment of Egyptian, Trigonella foenum - graecum L., Extract in comparison to pure diosgenin on experimentally induced non-alcoholic steatohepatitis: New targets via AMPK, RAR, and FXR pathways
Phytomedicine Plus
Acetyl-CoA carboxylase
Diosgenin
Farnesoid X receptor
Fenugreek
Non-alcoholic steatohepatitis
Retinoic acid receptor
title The prophylactic treatment of Egyptian, Trigonella foenum - graecum L., Extract in comparison to pure diosgenin on experimentally induced non-alcoholic steatohepatitis: New targets via AMPK, RAR, and FXR pathways
title_full The prophylactic treatment of Egyptian, Trigonella foenum - graecum L., Extract in comparison to pure diosgenin on experimentally induced non-alcoholic steatohepatitis: New targets via AMPK, RAR, and FXR pathways
title_fullStr The prophylactic treatment of Egyptian, Trigonella foenum - graecum L., Extract in comparison to pure diosgenin on experimentally induced non-alcoholic steatohepatitis: New targets via AMPK, RAR, and FXR pathways
title_full_unstemmed The prophylactic treatment of Egyptian, Trigonella foenum - graecum L., Extract in comparison to pure diosgenin on experimentally induced non-alcoholic steatohepatitis: New targets via AMPK, RAR, and FXR pathways
title_short The prophylactic treatment of Egyptian, Trigonella foenum - graecum L., Extract in comparison to pure diosgenin on experimentally induced non-alcoholic steatohepatitis: New targets via AMPK, RAR, and FXR pathways
title_sort prophylactic treatment of egyptian trigonella foenum graecum l extract in comparison to pure diosgenin on experimentally induced non alcoholic steatohepatitis new targets via ampk rar and fxr pathways
topic Acetyl-CoA carboxylase
Diosgenin
Farnesoid X receptor
Fenugreek
Non-alcoholic steatohepatitis
Retinoic acid receptor
url http://www.sciencedirect.com/science/article/pii/S2667031323000179
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