Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats

The rising prevalence of non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus has emerged as a global health challenge. Gossypetin (GTIN) is a natural flavonoid which has recently demonstrated antihyperglycaemic, antioxidant, and anti-inflammatory effects. Despite these fin...

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Main Authors: Karishma Naidoo, Andile Khathi
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/8/1834
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author Karishma Naidoo
Andile Khathi
author_facet Karishma Naidoo
Andile Khathi
author_sort Karishma Naidoo
collection DOAJ
description The rising prevalence of non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus has emerged as a global health challenge. Gossypetin (GTIN) is a natural flavonoid which has recently demonstrated antihyperglycaemic, antioxidant, and anti-inflammatory effects. Despite these findings, no studies have investigated its effects on liver health in the pre-diabetic state. Hence, this study aimed to investigate the effects of GTIN on liver health in diet-induced pre-diabetic male rats in the presence and absence of dietary intervention and to compare these effects with those of metformin (MET). Following 20 weeks of pre-diabetes induction, the animals were divided into six groups (<i>n</i> = 6) as follows: non-pre-diabetic (NPD) control, pre-diabetic (PD) control, and PD groups treated with GTIN (15 mg/kg body weight (bw)) or metformin (500 mg/kg bw) on either a normal diet or a high-fat, high-carbohydrate diet for 12 weeks. The results showed that the PD group had significantly higher liver triglycerides (TAG), liver weights, sterol regulatory binding element regulatory protein-1c (SREBP-1c), malondialdehyde (MDA) levels, and liver injury enzyme levels, along with decreased liver superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and plasma bilirubin levels in comparison to NPD. Histologically, there was an increased lipid droplet accumulation and structural disarray in the PD group. GTIN treatment significantly reduced liver TAGs, liver weights, and plasma SREBP-1c levels, as well as improved liver SOD and GPx activity while decreasing liver MDA levels and liver injury enzymes in comparison to the PD control. Notably, GTIN treatment increased plasma bilirubin levels. Liver histology in the GTIN-treated groups revealed decreased lipid droplet accumulation and improved tissue integrity. Similar results were observed for the liver parameters in the MET-treated groups. The findings of this study may suggest that GTIN and MET exhibit therapeutic effects on liver health in diet-induced pre-diabetes in both the presence and absence of diet intervention. Dietary intervention may confer beneficial effects on liver health, with the most favorable therapeutic outcomes observed through a combination of treatment with dietary intervention. Additionally, GTIN may exhibit greater hepatoprotective effects than MET in rats without dietary intervention.
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spelling doaj-art-1b4c28b7f74047f8a0db01526c26fcd22025-08-20T02:18:15ZengMDPI AGMolecules1420-30492025-04-01308183410.3390/molecules30081834Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley RatsKarishma Naidoo0Andile Khathi1Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South AfricaDepartment of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South AfricaThe rising prevalence of non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus has emerged as a global health challenge. Gossypetin (GTIN) is a natural flavonoid which has recently demonstrated antihyperglycaemic, antioxidant, and anti-inflammatory effects. Despite these findings, no studies have investigated its effects on liver health in the pre-diabetic state. Hence, this study aimed to investigate the effects of GTIN on liver health in diet-induced pre-diabetic male rats in the presence and absence of dietary intervention and to compare these effects with those of metformin (MET). Following 20 weeks of pre-diabetes induction, the animals were divided into six groups (<i>n</i> = 6) as follows: non-pre-diabetic (NPD) control, pre-diabetic (PD) control, and PD groups treated with GTIN (15 mg/kg body weight (bw)) or metformin (500 mg/kg bw) on either a normal diet or a high-fat, high-carbohydrate diet for 12 weeks. The results showed that the PD group had significantly higher liver triglycerides (TAG), liver weights, sterol regulatory binding element regulatory protein-1c (SREBP-1c), malondialdehyde (MDA) levels, and liver injury enzyme levels, along with decreased liver superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and plasma bilirubin levels in comparison to NPD. Histologically, there was an increased lipid droplet accumulation and structural disarray in the PD group. GTIN treatment significantly reduced liver TAGs, liver weights, and plasma SREBP-1c levels, as well as improved liver SOD and GPx activity while decreasing liver MDA levels and liver injury enzymes in comparison to the PD control. Notably, GTIN treatment increased plasma bilirubin levels. Liver histology in the GTIN-treated groups revealed decreased lipid droplet accumulation and improved tissue integrity. Similar results were observed for the liver parameters in the MET-treated groups. The findings of this study may suggest that GTIN and MET exhibit therapeutic effects on liver health in diet-induced pre-diabetes in both the presence and absence of diet intervention. Dietary intervention may confer beneficial effects on liver health, with the most favorable therapeutic outcomes observed through a combination of treatment with dietary intervention. Additionally, GTIN may exhibit greater hepatoprotective effects than MET in rats without dietary intervention.https://www.mdpi.com/1420-3049/30/8/1834gossypetinNAFLDliver injuryflavonoidssteatosishigh-caloric diets
spellingShingle Karishma Naidoo
Andile Khathi
Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats
Molecules
gossypetin
NAFLD
liver injury
flavonoids
steatosis
high-caloric diets
title Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats
title_full Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats
title_fullStr Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats
title_full_unstemmed Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats
title_short Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats
title_sort investigating the effects of gossypetin on liver health in diet induced pre diabetic male sprague dawley rats
topic gossypetin
NAFLD
liver injury
flavonoids
steatosis
high-caloric diets
url https://www.mdpi.com/1420-3049/30/8/1834
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AT andilekhathi investigatingtheeffectsofgossypetinonliverhealthindietinducedprediabeticmalespraguedawleyrats