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Modulation of hyperglycemia and TNFα-mediated inflammation by helichrysum and grapefruit extracts in diabetic db/db
Ana Laura de la Garza1, Usune Etxeberria, Sara Palacios-Ortega
1Department of Nutrition, Food Science and Physiology, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Navarra, Spain. jalfmtz@unav.es.
Abstract:
Type-2 diabetes is associated with a chronic low-grade systemic inflammation accompanied by an increased production of adipokines/cytokines by obese adipose tissue. The search for new antidiabetic drugs with different mechanisms of action, such as insulin sensitizers, insulin secretagogues and α-glucosidase inhibitors, has directed the focus on the potential use of flavonoids in the management of type-2 diabetes. Thirty six diabetic male C57BL/6J db/db mice were fed a standard diet and randomly assigned into four experimental groups: non-treated control, (n = 8); acarbose (5 mg per kg bw, n = 8); helichrysum (1 g per kg bw, n = 10) and grapefruit (0.5 g per kg bw, n = 10) for 6 weeks. The mRNA expression in pancreas, liver and epididymal adipose tissue was determined by RT-PCR. DNA methylation was quantified in epididymal fat using pyrosequencing. Mice supplemented with helichrysum and grapefruit extracts showed a significant decrease in fasting glucose levels (p < 0.05). A possible mechanism of action could be the up-regulation of liver glucokinase (p < 0.05). The antihyperglycemic effect of both extracts was accompanied by decreased mRNA expression of some proinflammatory genes (monocyte chemotactic protein-1, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-kappaB) in the liver and epididymal adipose tissue. The CpG3 site of TNFα, located 5 bp downstream of the transcription start site, showed increased DNA methylation in the grapefruit group compared with the non-treated group (p < 0.01). In conclusion, helichrysum and grapefruit extracts improved hyperglycemia through the regulation of glucose metabolism in the liver and reduction of the expression of proinflammatory genes in the liver and visceral fat. The hypermethylation of TNFα in adipose tissue may contribute to reduce the inflammation associated with diabetes and obesity.
Insights
Helichrysum and grapefruit extracts effectively lowered blood sugar in diabetic mice by regulating liver glucose metabolism and reducing inflammation. These natural compounds may offer a new approach to managing type-2 diabetes and its associated inflammatory conditions.
Area of Science:
- Metabolic disorders
- Pharmacology
- Immunology
Background:
- Type-2 diabetes is linked to chronic inflammation and altered cytokine production from adipose tissue.
- Flavonoids are being investigated for their potential antidiabetic properties, targeting mechanisms like insulin sensitization and glucose inhibition.
- Obesity exacerbates inflammation, contributing to the complex pathophysiology of type-2 diabetes.
Purpose of the Study:
- To evaluate the efficacy of helichrysum and grapefruit extracts in managing type-2 diabetes in a mouse model.
- To investigate the molecular mechanisms underlying the antihyperglycemic and anti-inflammatory effects of these botanical extracts.
- To explore the role of gene expression and DNA methylation in the therapeutic action of helichrysum and grapefruit.
Main Methods:
- A study involving 36 diabetic male C57BL/6J db/db mice divided into control, acarbose, helichrysum, and grapefruit groups.
- Administration of helichrysum (1 g/kg) and grapefruit (0.5 g/kg) extracts for 6 weeks, alongside a standard diet.
- Analysis of mRNA expression in pancreas, liver, and adipose tissue using RT-PCR and quantification of DNA methylation in epididymal fat via pyrosequencing.
Main Results:
- Helichrysum and grapefruit extracts significantly reduced fasting glucose levels (p < 0.05) and upregulated liver glucokinase.
- A decrease in mRNA expression of proinflammatory genes (e.g., TNF-α, NF-κB) was observed in the liver and adipose tissue of treated mice.
- Grapefruit extract notably increased DNA methylation at the TNFα CpG3 site in adipose tissue (p < 0.01), suggesting epigenetic modulation of inflammation.
Conclusions:
- Helichrysum and grapefruit extracts demonstrate significant antihyperglycemic effects in type-2 diabetic mice.
- These extracts modulate glucose metabolism and reduce inflammation by downregulating key proinflammatory genes in the liver and visceral fat.
- Epigenetic modifications, such as TNFα hypermethylation, may play a role in the anti-inflammatory benefits of grapefruit extract in diabetes and obesity.
