4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats

Background: Hyperglycemia induced diabetic complications as well as dysfunction of multiple organs is closely related to the increased inflammation and oxidative stress (OS). 4-hydroxyisoleucine (4-HIL), a major constituent of Trigonella foenum-graecum L. shown to have anti-diabetic effects. However...

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Autores principales:	Rupali Singh, Karan Singh Yadav, Ramanand Prajapati, Sharad Sharma, Srikanta Kumar Rath, Tadigoppula Narender, Madhav Nilakanth Mugale
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	4-hydroxyisoleucine Antioxidant Diabetic complication Inflammation Oxidative stress Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/92ae82f14bdc4bdb98125d9cb29c2586
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spelling	oai:doaj.org-article:92ae82f14bdc4bdb98125d9cb29c25862021-11-10T04:43:49Z4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats2667-031310.1016/j.phyplu.2021.100141https://doaj.org/article/92ae82f14bdc4bdb98125d9cb29c25862022-02-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2667031321001238https://doaj.org/toc/2667-0313Background: Hyperglycemia induced diabetic complications as well as dysfunction of multiple organs is closely related to the increased inflammation and oxidative stress (OS). 4-hydroxyisoleucine (4-HIL), a major constituent of Trigonella foenum-graecum L. shown to have anti-diabetic effects. However, its potential mechanism against diabetic complications in the model of metabolic syndrome have not yet been characterized. Purpose: The present study aimed to investigate the ameliorative effects of 4-HIL in rat model of metabolic syndrome and to explore the possible mechanism of action. Methods: Male Sprague dawley rat of 6 -7 weeks were administrated with 4-HIL by oral gavage from 12 to 20 weeks after development of complications. At the end of the study, all animals were sacrificed. Tissues and blood samples were collected for histopathologic and biochemical analysis. Serum metabolic parameters, level of triglycerides, glycated hemoglobin, activities of antioxidant enzymes were estimated. Pathological changes in the tissues were assessed by Hematoxylin – Eosin (H & E), Masson's trichrome and Periodic Acid - Schiff (PAS) staining. In vivo gene expressions were demonstrated by Western blotting. Results: Oral administration of 4-HIL (200 mg kg−1) reduced the body hyperglycemia, glycated hemoglobin (HbA1c), creatinine, blood urea nitrogen (BUN), triglyceride and restored the histopathological indices when compared with the diabetic control group. The 4-HIL increased the activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) in tissues samples. It down-regulate the expression of vascular endothelial growth factor (VEGF), tissue injury molecule-1 (TIM-1), insulin receptor (INSULIN R) and transforming growth factor beta 1 (TGF-β1) mediated inflammatory response in all the tissues. Moreover, it exhibits protective effect against oxidative stress by activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway-related proteins in the tissues. Conclusion: The findings highlight the beneficial role of 4-HIL in diabetic complications by decreasing inflammatory response and oxidative stress through TGF-β1 signaling pathway and activation of Nrf2 gene expression respectively in addition to its effect on glycemic control.Rupali SinghKaran Singh YadavRamanand PrajapatiSharad SharmaSrikanta Kumar RathTadigoppula NarenderMadhav Nilakanth MugaleElsevierarticle4-hydroxyisoleucineAntioxidantDiabetic complicationInflammationOxidative stressOther systems of medicineRZ201-999ENPhytomedicine Plus, Vol 2, Iss 1, Pp 100141- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	4-hydroxyisoleucine Antioxidant Diabetic complication Inflammation Oxidative stress Other systems of medicine RZ201-999
spellingShingle	4-hydroxyisoleucine Antioxidant Diabetic complication Inflammation Oxidative stress Other systems of medicine RZ201-999 Rupali Singh Karan Singh Yadav Ramanand Prajapati Sharad Sharma Srikanta Kumar Rath Tadigoppula Narender Madhav Nilakanth Mugale 4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats
description	Background: Hyperglycemia induced diabetic complications as well as dysfunction of multiple organs is closely related to the increased inflammation and oxidative stress (OS). 4-hydroxyisoleucine (4-HIL), a major constituent of Trigonella foenum-graecum L. shown to have anti-diabetic effects. However, its potential mechanism against diabetic complications in the model of metabolic syndrome have not yet been characterized. Purpose: The present study aimed to investigate the ameliorative effects of 4-HIL in rat model of metabolic syndrome and to explore the possible mechanism of action. Methods: Male Sprague dawley rat of 6 -7 weeks were administrated with 4-HIL by oral gavage from 12 to 20 weeks after development of complications. At the end of the study, all animals were sacrificed. Tissues and blood samples were collected for histopathologic and biochemical analysis. Serum metabolic parameters, level of triglycerides, glycated hemoglobin, activities of antioxidant enzymes were estimated. Pathological changes in the tissues were assessed by Hematoxylin – Eosin (H & E), Masson's trichrome and Periodic Acid - Schiff (PAS) staining. In vivo gene expressions were demonstrated by Western blotting. Results: Oral administration of 4-HIL (200 mg kg−1) reduced the body hyperglycemia, glycated hemoglobin (HbA1c), creatinine, blood urea nitrogen (BUN), triglyceride and restored the histopathological indices when compared with the diabetic control group. The 4-HIL increased the activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) in tissues samples. It down-regulate the expression of vascular endothelial growth factor (VEGF), tissue injury molecule-1 (TIM-1), insulin receptor (INSULIN R) and transforming growth factor beta 1 (TGF-β1) mediated inflammatory response in all the tissues. Moreover, it exhibits protective effect against oxidative stress by activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway-related proteins in the tissues. Conclusion: The findings highlight the beneficial role of 4-HIL in diabetic complications by decreasing inflammatory response and oxidative stress through TGF-β1 signaling pathway and activation of Nrf2 gene expression respectively in addition to its effect on glycemic control.
format	article
author	Rupali Singh Karan Singh Yadav Ramanand Prajapati Sharad Sharma Srikanta Kumar Rath Tadigoppula Narender Madhav Nilakanth Mugale
author_facet	Rupali Singh Karan Singh Yadav Ramanand Prajapati Sharad Sharma Srikanta Kumar Rath Tadigoppula Narender Madhav Nilakanth Mugale
author_sort	Rupali Singh
title	4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats
title_short	4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats
title_full	4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats
title_fullStr	4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats
title_full_unstemmed	4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats
title_sort	4-hil mitigates type-2 diabetic complications through inhibiting inflammation and nrf2 mediated oxidative stress in rats
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/92ae82f14bdc4bdb98125d9cb29c2586
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4-HIL mitigates type-2 diabetic complications through inhibiting inflammation and Nrf2 mediated oxidative stress in rats

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