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Crocin ameliorates MicroRNAs-associated ER stress in type 2 diabetes induced by methylglyoxal
Vahid Radmehr1, Akram Ahangarpour2, Seyyed Ali Mard2,3
1Student Research Committee, Department of Physiology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Objectives:
Methylglyoxal (MG) provokes endoplasmic reticulum (ER) stress in β-cells and triggers pancreatic β-cell dysfunction. Crocin has anti-diabetic properties. The present study investigated whether crocin prevented pancreas damages induced by MG.
Materials And Methods:
Diabetes was induced by MG administration (600 mg/kg/day, PO). On the fourteenth day, after proving hyperglycemia, crocin (15, 30, and 60 mg/kg) and metformin (MT) (150 mg/kg) were used for detoxification of MG until the end of the experiment. The animals were divided into 6 groups: 1) control, 2) diabetic by MG, 3) MG + crocin 15 mg/kg, 4) MG + crocin 30 mg/kg, 5) MG + crocin 60 mg/kg, and 6) MG + MT. The data were analyzed by one-way analysis of variance and significant differences were compared by Tukey and Bonferroni tests (P<0.05). Biochemical assays, antioxidant evaluation, and microRNAs expression associated with ER stress were assessed.
Results:
MG induced hyperglycemia, insulin resistance, and dyslipidemia (P<0.001). Crocin and MT significantly ameliorated β-cell function through reduction of fasting blood glucose, malondialdehyde levels (P<0.001), and significant elevation of anti-oxidant enzyme activity accompanied by regulation of glutathione and glyoxalase1-Nrf2 in MG induced diabetic mice. Crocin and MT significantly down-regulated microRNAs 204, 216b, 192, and 29a expression (P<0.001). Crocin (60 mg/kg) (P<0.01) and MT (P<0.001) could improve diameter of pancreatic islets in MG treated mice.
Conclusion:
Crocin prevents the progression of diabetes through modulating ER stress-associated microRNAs and GLO1 activity with the helpful effects of glutathione and Nrf2.
Insights
Crocin effectively combats diabetes by reducing methylglyoxal-induced damage in pancreatic cells. This natural compound modulates endoplasmic reticulum stress and improves antioxidant defenses, offering a potential therapeutic strategy for diabetes management.
Area of Science:
- Endocrinology
- Biochemistry
- Pharmacology
Background:
- Methylglyoxal (MG) is a key factor in endoplasmic reticulum (ER) stress and pancreatic β-cell dysfunction, contributing to diabetes progression.
- Crocin, a compound found in saffron, exhibits known anti-diabetic properties.
- Understanding crocin's protective mechanisms against MG-induced pancreatic damage is crucial for developing novel diabetes therapies.
Purpose of the Study:
- To investigate the protective effects of crocin against methylglyoxal (MG)-induced pancreatic damage and β-cell dysfunction.
- To evaluate crocin's impact on ER stress markers, oxidative stress, and related microRNAs in a mouse model of diabetes.
- To compare the efficacy of crocin with metformin in mitigating MG-induced diabetic complications.
Main Methods:
- Diabetes was induced in mice using methylglyoxal (MG).
- Animals were treated with varying doses of crocin (15, 30, 60 mg/kg) or metformin (150 mg/kg).
- Evaluated biochemical assays, antioxidant status, microRNA expression (associated with ER stress), and pancreatic islet morphology.
Main Results:
- MG administration led to hyperglycemia, insulin resistance, and dyslipidemia.
- Crocin and metformin significantly reduced fasting blood glucose and malondialdehyde levels.
- Crocin treatment elevated antioxidant enzyme activity, regulated glutathione and glyoxalase1-Nrf2, and downregulated specific ER stress-associated microRNAs, improving pancreatic islet structure.
Conclusions:
- Crocin effectively prevents diabetes progression by mitigating MG-induced pancreatic damage.
- The protective effects are attributed to modulating ER stress-associated microRNAs and glyoxalase 1 (GLO1) activity.
- Crocin enhances antioxidant defenses via glutathione and Nrf2 pathways, supporting β-cell function.
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