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Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model

CONTEXT: α-Mangosteen (α-MG) attenuates insulin resistance (IR). However, it is still unknown whether α-MG could alleviate hepatic manifestations in IR rats. OBJECTIVE: To investigate the effect of α-MG on alleviating hepatic manifestations in IR rats through AMP-activated protein kinase (AMPK) and...

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Autores principales: Soetikno, Vivian, Andini, Prisma, Iskandar, Miskiyah, Matheos, Clark Christensen, Herdiman, Joshua Alward, Kyle, Iqbal Kevin, Suma, Muhammad Nur Imaduddin, Louisa, Melva, Estuningtyas, Ari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969969/
https://www.ncbi.nlm.nih.gov/pubmed/36655319
http://dx.doi.org/10.1080/13880209.2023.2166086
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author Soetikno, Vivian
Andini, Prisma
Iskandar, Miskiyah
Matheos, Clark Christensen
Herdiman, Joshua Alward
Kyle, Iqbal Kevin
Suma, Muhammad Nur Imaduddin
Louisa, Melva
Estuningtyas, Ari
author_facet Soetikno, Vivian
Andini, Prisma
Iskandar, Miskiyah
Matheos, Clark Christensen
Herdiman, Joshua Alward
Kyle, Iqbal Kevin
Suma, Muhammad Nur Imaduddin
Louisa, Melva
Estuningtyas, Ari
author_sort Soetikno, Vivian
collection PubMed
description CONTEXT: α-Mangosteen (α-MG) attenuates insulin resistance (IR). However, it is still unknown whether α-MG could alleviate hepatic manifestations in IR rats. OBJECTIVE: To investigate the effect of α-MG on alleviating hepatic manifestations in IR rats through AMP-activated protein kinase (AMPK) and sterol-regulatory element-binding protein-1 (SREBP-1) pathway. MATERIALS AND METHODS: IR was induced by exposing male Sprague-Dawley rats (180–200 g) to high-fat/high-glucose diet and low-dose injection of streptozotocin (HF/HG/STZ), then treated with α-MG at a dose of 100 or 200 mg/kg/day for 8 weeks. At the end of the study (11 weeks), serum and liver were harvested for biochemical analysis, and the activity of AMPK, SREBP-1c, acetyl-CoA carboxylase (ACC), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, insulin receptor substrate (IRS)-1, Bax and liver histopathology were analyzed. RESULTS: α-MG at both doses significantly lowered ALT, AST, triglyceride, and cholesterol total by 16.5, 15.7, 38, and 36%, respectively. These beneficial effects of α-MG are associated with the downregulation of the IR-induced inflammation in the liver. Furthermore, α-MG, at both doses, activated AMPK by 24–29 times and reduced SREBP-1c by 44–50% as well as ACC expression by 19–31% similar to metformin. All treatment groups showed liver histopathology improvement regarding fat deposition in the liver. CONCLUSIONS: Based on the findings demonstrated, α-MG protected against HF/HG/STZ-induced hepatic manifestations of the IR rats, at least in part via the modulation of the AMPK/SREBP-1c/ACC pathway and it could be a potential drug candidate to prevent IR-induced hepatic manifestations.
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spelling pubmed-99699692023-02-28 Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model Soetikno, Vivian Andini, Prisma Iskandar, Miskiyah Matheos, Clark Christensen Herdiman, Joshua Alward Kyle, Iqbal Kevin Suma, Muhammad Nur Imaduddin Louisa, Melva Estuningtyas, Ari Pharm Biol Research Article CONTEXT: α-Mangosteen (α-MG) attenuates insulin resistance (IR). However, it is still unknown whether α-MG could alleviate hepatic manifestations in IR rats. OBJECTIVE: To investigate the effect of α-MG on alleviating hepatic manifestations in IR rats through AMP-activated protein kinase (AMPK) and sterol-regulatory element-binding protein-1 (SREBP-1) pathway. MATERIALS AND METHODS: IR was induced by exposing male Sprague-Dawley rats (180–200 g) to high-fat/high-glucose diet and low-dose injection of streptozotocin (HF/HG/STZ), then treated with α-MG at a dose of 100 or 200 mg/kg/day for 8 weeks. At the end of the study (11 weeks), serum and liver were harvested for biochemical analysis, and the activity of AMPK, SREBP-1c, acetyl-CoA carboxylase (ACC), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, insulin receptor substrate (IRS)-1, Bax and liver histopathology were analyzed. RESULTS: α-MG at both doses significantly lowered ALT, AST, triglyceride, and cholesterol total by 16.5, 15.7, 38, and 36%, respectively. These beneficial effects of α-MG are associated with the downregulation of the IR-induced inflammation in the liver. Furthermore, α-MG, at both doses, activated AMPK by 24–29 times and reduced SREBP-1c by 44–50% as well as ACC expression by 19–31% similar to metformin. All treatment groups showed liver histopathology improvement regarding fat deposition in the liver. CONCLUSIONS: Based on the findings demonstrated, α-MG protected against HF/HG/STZ-induced hepatic manifestations of the IR rats, at least in part via the modulation of the AMPK/SREBP-1c/ACC pathway and it could be a potential drug candidate to prevent IR-induced hepatic manifestations. Taylor & Francis 2023-01-18 /pmc/articles/PMC9969969/ /pubmed/36655319 http://dx.doi.org/10.1080/13880209.2023.2166086 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Soetikno, Vivian
Andini, Prisma
Iskandar, Miskiyah
Matheos, Clark Christensen
Herdiman, Joshua Alward
Kyle, Iqbal Kevin
Suma, Muhammad Nur Imaduddin
Louisa, Melva
Estuningtyas, Ari
Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model
title Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model
title_full Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model
title_fullStr Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model
title_full_unstemmed Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model
title_short Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model
title_sort alpha-mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969969/
https://www.ncbi.nlm.nih.gov/pubmed/36655319
http://dx.doi.org/10.1080/13880209.2023.2166086
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