9 research outputs found
Modulation of hyperglycemia and TNF[alfa]-mediated inflammation by helichrysum and grapefruit extracts in diabetic db/db mice
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 Œ 8); acarbose (5 mg per kg bw, n Œ 8);
helichrysum (1 g per kg bw, n Œ 10) and grapefruit (0.5 g per kg bw, n Œ 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
Modulation of hyperglycemia and TNF[alfa]-mediated inflammation by helichrysum and grapefruit extracts in diabetic db/db mice
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 Œ 8); acarbose (5 mg per kg bw, n Œ 8);
helichrysum (1 g per kg bw, n Œ 10) and grapefruit (0.5 g per kg bw, n Œ 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
The interaction of diadenosine polyphosphates with P(2X)-receptors in the guinea-pig isolated vas deferens
1. The site(s) at which diadenosine 5âČ,5âČâČâČ-P(1),P(4)-tetraphosphate (AP(4)A) and diadenosine 5âČ, 5âČâČâČ-P(1),P(5)-pentaphosphate (AP(5)A) act to evoke contraction of the guinea-pig isolated vas deferens was studied by use of a series of P(2)-receptor antagonists and the ecto-ATPase inhibitor 6-N,N-diethyl-D-ÎČ,Îł-dibromomethyleneATP (ARL 67156). 2. Pyridoxalphosphate-6-azophenyl-2âČ,4âČ-disulphonic acid (PPADS) (300ânMâ30âÎŒM), suramin (3â100âÎŒM) and pyridoxal-5âČ-phosphate (P-5-P) (3â1000âÎŒM) inhibited contractions evoked by equi-effective concentrations of AP(5)A (3âÎŒM), AP(4)A (30âÎŒM) and α,ÎČ-methyleneATP (α,ÎČ-meATP) (1âÎŒM), in a concentration-dependent manner and abolished them at the highest concentrations used. 3. PPADS was more potent than suramin, which in turn was more potent than P-5-P. PPADS inhibited AP(5)A, AP(4)A and α,ÎČ-meATP with similar IC(50) values. No significant difference was found between IC(50) values for suramin against α,ÎČ-meATP and AP(5)A or α,ÎČ-meATP and AP(4)A, but suramin was more than 2.5 times more potent against AP(4)A than AP(5)A. P-5-P showed the same pattern of antagonism. 4. Desensitization of the P(2X1)-receptor by α,ÎČ-meATP abolished contractions evoked by AP(5)A (3âÎŒM) and AP(4)A (30âÎŒM), but had no effect on those elicited by noradrenaline (100âÎŒM). 5. ARL 67156 (100âÎŒM) reversibly potentiated contractions evoked by AP(4)A (30âÎŒM) by 61%, but caused a small, significant decrease in the mean response to AP(5)A (3âÎŒM). 6. It is concluded that AP(4)A and AP(5)A act at the P(2X1)-receptor, or a site similar to the P(2X1)-receptor, to evoke contraction of the guinea-pig isolated vas deferens. Furthermore, the potency of AP(4)A, but not AP(5)A, appears to be inhibited by an ecto-enzyme which is sensitive to ARL 67156