Modulation of hyperglycemia and TNFα-mediated inflammation by helichrysum and grapefruit extracts in diabetic db/db mice

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 aglucosidase 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 ¼ 8); acarbose (5 mg per kg bw, n ¼ 8);helichrysum (1 g per kg bw, n ¼ 10) and grapefruit (0.5 g per kg bw, n ¼ 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-a, cyclooxygenase-2, nuclear factorkappaB) in the liver and epididymal adipose tissue. The CpG3 site of TNFa, 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 TNFa in adipose tissue may contribute to reduce the inflammation associated with diabetes and obesity.

Hypoglycemic effects of Zanthoxylum alkylamides by enhancing glucose metabolism and ameliorating pancreatic dysfunction in streptozotocin-induced diabetic rats

“…35,36 In our study, the levels of blood glucose and hepatic glycogen were significantly reversed after the rats were treated with alkylamides ( Fig. 40 Our results indicated that alkylamide treatment increased the GK expression and downregulated PEPCK and G6Pase expression levels in the liver of diabetic rats (Fig. On the basis of these findings, we hypothesized that alkylamides may modulate the critical enzymes of glycolysis and glycogen synthesis in the liver.…”

Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity

“…Flavonoid effects on inflammatory pathways NF-κB plays a key role in the intestinal inflammatory response (75) ; therefore, the compounds that could modulate this inflammatory pathway are an interesting field of investigation. Flavonoid-mediated modulation of the inflammatory response has been extensively studied in several in vivo and in vitro models (76)(77)(78)(79)(80) ; however, there are fewer studies regarding its effects on intestinal inflammation ( Table 1).…”

Biocompounds Attenuating the Development of Obesity and Insulin Resistance Produced by a High-fat Sucrose Diet

“…In the recent decades, the use of phenolic phytochemicals or natural extracts for the management of obesity and other related diseases has been a scientific focus [7,8]. In this sense, polyphenols such as flavanones (naringin), simple phenolic acids (coumaric acid and chlorogenic acid), curcuminoids (curcumin) [9], and other biocompounds, as for instance leucine, a branched-chain amino acid [10], have been suggested to exert potential health beneficial effects in the context of obesity.…”