Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells

Abstract Background Paliurus spina-christi Mill. (PSC) fruit is frequently used in the treatment of diabetes mellitus in Mediterranean regions. Here, we investigated the effects of various PSC fruit extracts (PSC-FEs) on glucose consumption and some key mediators of insulin signaling pathways in hig...

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Main Authors: Seyedeh Mona Mousavi Esfahani, Parastoo Tarighi, Kosar Dianat, Tabarek Mahdi Ashour, Negar Mottaghi-Dastjerdi, Mehdi Aghsami, Mahsa Sabernavaei, Hamed Montazeri
Format: Article
Language:English
Published: BMC 2023-05-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-023-03977-y
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author Seyedeh Mona Mousavi Esfahani
Parastoo Tarighi
Kosar Dianat
Tabarek Mahdi Ashour
Negar Mottaghi-Dastjerdi
Mehdi Aghsami
Mahsa Sabernavaei
Hamed Montazeri
author_facet Seyedeh Mona Mousavi Esfahani
Parastoo Tarighi
Kosar Dianat
Tabarek Mahdi Ashour
Negar Mottaghi-Dastjerdi
Mehdi Aghsami
Mahsa Sabernavaei
Hamed Montazeri
author_sort Seyedeh Mona Mousavi Esfahani
collection DOAJ
description Abstract Background Paliurus spina-christi Mill. (PSC) fruit is frequently used in the treatment of diabetes mellitus in Mediterranean regions. Here, we investigated the effects of various PSC fruit extracts (PSC-FEs) on glucose consumption and some key mediators of insulin signaling pathways in high glucose and high insulin-induced insulin-resistant HepG2 cells. Methods The effects of methanolic, chloroform and total extracts on cell proliferation were assessed by the MTT assay. The potential of non-toxic extracts on glucose utilization in insulin-resistant HepG2 cells was checked using a glucose oxidase assay. AKT and AMP-activated protein kinase (AMPK) pathway activation and mRNA expression levels of insulin receptor (INSR), glucose transporter 1 (GLUT1), and glucose transporters 4 (GLUT4) were determined by western blotting and real-time PCR, respectively. Results We found that high concentrations of methanolic and both low and high concentrations of total extracts were able to enhance glucose uptake in an insulin-resistant cell line model. Moreover, AKT and AMPK phosphorylation were significantly increased by the high strength of methanolic extract, while total extract raised AMPK activation at low and high concentrations. Also, GLUT 1, GLUT 4, and INSR were elevated by both methanolic and total extracts. Conclusions Ultimately, our results shed new light on methanolic and total PSC-FEs as sources of potential anti-diabetic medications, restoring glucose consumption and uptake in insulin-resistant HepG2 cells. These could be at least in part due to re-activating AKT and AMPK signaling pathways and also increased expression of INSR, GLUT1, and GLUT4. Overall, active constituents present in methanolic and total extracts of PCS are appropriate anti-diabetic agents and explain the use of these PSC fruits in traditional medicine for the treatment of diabetes.
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spelling doaj.art-f2b46d1c66b94ff29dfb40c679a8d9d52023-05-14T11:08:08ZengBMCBMC Complementary Medicine and Therapies2662-76712023-05-012311910.1186/s12906-023-03977-yPaliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cellsSeyedeh Mona Mousavi Esfahani0Parastoo Tarighi1Kosar Dianat2Tabarek Mahdi Ashour3Negar Mottaghi-Dastjerdi4Mehdi Aghsami5Mahsa Sabernavaei6Hamed Montazeri7Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical SciencesDepartment of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical SciencesDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical SciencesDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical SciencesDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical SciencesDepartment of Pharmacology and Toxicology, School of Pharmacy, Iran University of Medical SciencesDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical SciencesDepartment of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical SciencesAbstract Background Paliurus spina-christi Mill. (PSC) fruit is frequently used in the treatment of diabetes mellitus in Mediterranean regions. Here, we investigated the effects of various PSC fruit extracts (PSC-FEs) on glucose consumption and some key mediators of insulin signaling pathways in high glucose and high insulin-induced insulin-resistant HepG2 cells. Methods The effects of methanolic, chloroform and total extracts on cell proliferation were assessed by the MTT assay. The potential of non-toxic extracts on glucose utilization in insulin-resistant HepG2 cells was checked using a glucose oxidase assay. AKT and AMP-activated protein kinase (AMPK) pathway activation and mRNA expression levels of insulin receptor (INSR), glucose transporter 1 (GLUT1), and glucose transporters 4 (GLUT4) were determined by western blotting and real-time PCR, respectively. Results We found that high concentrations of methanolic and both low and high concentrations of total extracts were able to enhance glucose uptake in an insulin-resistant cell line model. Moreover, AKT and AMPK phosphorylation were significantly increased by the high strength of methanolic extract, while total extract raised AMPK activation at low and high concentrations. Also, GLUT 1, GLUT 4, and INSR were elevated by both methanolic and total extracts. Conclusions Ultimately, our results shed new light on methanolic and total PSC-FEs as sources of potential anti-diabetic medications, restoring glucose consumption and uptake in insulin-resistant HepG2 cells. These could be at least in part due to re-activating AKT and AMPK signaling pathways and also increased expression of INSR, GLUT1, and GLUT4. Overall, active constituents present in methanolic and total extracts of PCS are appropriate anti-diabetic agents and explain the use of these PSC fruits in traditional medicine for the treatment of diabetes.https://doi.org/10.1186/s12906-023-03977-yPaliurus spina-christi MillDiabetesAMP-activated protein kinase (AMPK)AKTGLUT1GLUT4
spellingShingle Seyedeh Mona Mousavi Esfahani
Parastoo Tarighi
Kosar Dianat
Tabarek Mahdi Ashour
Negar Mottaghi-Dastjerdi
Mehdi Aghsami
Mahsa Sabernavaei
Hamed Montazeri
Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells
BMC Complementary Medicine and Therapies
Paliurus spina-christi Mill
Diabetes
AMP-activated protein kinase (AMPK)
AKT
GLUT1
GLUT4
title Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells
title_full Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells
title_fullStr Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells
title_full_unstemmed Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells
title_short Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells
title_sort paliurus spina christi mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in hepg2 insulin resistant cells
topic Paliurus spina-christi Mill
Diabetes
AMP-activated protein kinase (AMPK)
AKT
GLUT1
GLUT4
url https://doi.org/10.1186/s12906-023-03977-y
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