Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway

Abstract Diabetes mellitus is a common metabolic disorder. About two-thirds of diabetic patients develop diabetic cardiomyopathy (DCM), which becomes a challenging issue as it severely threatens the patient’s life. Hyperglycemia and the resulting advanced glycated end products (AGE) and their recept...

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Main Authors: Eman A. E. Farrag, Maha O. Hammad, Sally M. Safwat, Shereen Hamed, Doaa Hellal
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-37678-w
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author Eman A. E. Farrag
Maha O. Hammad
Sally M. Safwat
Shereen Hamed
Doaa Hellal
author_facet Eman A. E. Farrag
Maha O. Hammad
Sally M. Safwat
Shereen Hamed
Doaa Hellal
author_sort Eman A. E. Farrag
collection DOAJ
description Abstract Diabetes mellitus is a common metabolic disorder. About two-thirds of diabetic patients develop diabetic cardiomyopathy (DCM), which becomes a challenging issue as it severely threatens the patient’s life. Hyperglycemia and the resulting advanced glycated end products (AGE) and their receptor (RAGE)/High Mobility Group Box-1 (HMGB-1) molecular pathway are thought to be key players. Recently, artemisinin (ART) has gained more attention owing to its potent biological activities beyond its antimalarial effect. Herein, we aim to evaluate the effect of ART on DCM and the possible underlying mechanisms. Twenty-four male Sprague–Dawley rats were divided into: control, ART, type 2 diabetic and type 2 diabetic treated with ART groups. At the end of the research, the ECG was recorded, then the heart weight to body weight (HW/BW) ratio, fasting blood glucose, serum insulin and HOMA-IR were evaluated. Cardiac biomarkers (CK-MB and LDH), oxidative stress markers, IL-1β, AGE, RAGE and HMGB-1 expression were also measured. The heart specimens were stained for H&E as well as Masson’s trichrome. DCM induced disturbances in all studied parameters; contrary to this, ART improved these insults. Our study concluded that ART could improve DCM through modulation of the AGE-RAGE/HMGB-1 signaling pathway, with subsequent impacts on oxidative stress, inflammation and fibrosis. ART could therefore be a promising therapy for the management of DCM.
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spelling doaj.art-4a4b3af211c644a3978e44c1efad07a72023-07-09T11:12:17ZengNature PortfolioScientific Reports2045-23222023-07-0113111310.1038/s41598-023-37678-wArtemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathwayEman A. E. Farrag0Maha O. Hammad1Sally M. Safwat2Shereen Hamed3Doaa Hellal4Department of Clinical Pharmacology, Faculty of Medicine, Mansoura UniversityDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura UniversityDepartment of Physiology, Faculty of Medicine, Mansoura UniversityDepartment of Medical Histology, Faculty of Medicine, Mansoura UniversityDepartment of Clinical Pharmacology, Faculty of Medicine, Mansoura UniversityAbstract Diabetes mellitus is a common metabolic disorder. About two-thirds of diabetic patients develop diabetic cardiomyopathy (DCM), which becomes a challenging issue as it severely threatens the patient’s life. Hyperglycemia and the resulting advanced glycated end products (AGE) and their receptor (RAGE)/High Mobility Group Box-1 (HMGB-1) molecular pathway are thought to be key players. Recently, artemisinin (ART) has gained more attention owing to its potent biological activities beyond its antimalarial effect. Herein, we aim to evaluate the effect of ART on DCM and the possible underlying mechanisms. Twenty-four male Sprague–Dawley rats were divided into: control, ART, type 2 diabetic and type 2 diabetic treated with ART groups. At the end of the research, the ECG was recorded, then the heart weight to body weight (HW/BW) ratio, fasting blood glucose, serum insulin and HOMA-IR were evaluated. Cardiac biomarkers (CK-MB and LDH), oxidative stress markers, IL-1β, AGE, RAGE and HMGB-1 expression were also measured. The heart specimens were stained for H&E as well as Masson’s trichrome. DCM induced disturbances in all studied parameters; contrary to this, ART improved these insults. Our study concluded that ART could improve DCM through modulation of the AGE-RAGE/HMGB-1 signaling pathway, with subsequent impacts on oxidative stress, inflammation and fibrosis. ART could therefore be a promising therapy for the management of DCM.https://doi.org/10.1038/s41598-023-37678-w
spellingShingle Eman A. E. Farrag
Maha O. Hammad
Sally M. Safwat
Shereen Hamed
Doaa Hellal
Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway
Scientific Reports
title Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway
title_full Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway
title_fullStr Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway
title_full_unstemmed Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway
title_short Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway
title_sort artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of age rage hmgb 1 signaling pathway
url https://doi.org/10.1038/s41598-023-37678-w
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