الفهرس 
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Abstract
The aim of the present study was to clarify the effect of Cynara scolymus leaf and flower head extracts administered orally on different biochemical parameters in streptozotocin diabetic rats. For performing the present work, adult male albino rats (120±20 g) were used.
After induction of NA/STZ diabetes, the rats were divided into the following groups: Normal group (G1) was administered the equivalent volume of the 1% carboxymethylcellulose (1%CMC) by oral gavage daily for 28 days. Diabetic group (G2) was administered the equivalent volume of the 1%CMC by oral gavage daily for 28 days. Diabetic group treated with Cynara scolymus leaf extract (G3) was administered Cynara scolymus leaf extract at dose of 100 mg/kg b.wt by oral gavage daily for 28 days. Diabetic group treated with Cynara scolymus flowers head extract (G4) was administered Cynara scolymus flowers head extract at dose of 100 mg/kg b.wt by oral gavage daily for 28 days.
At the end of the 28 days of starting treatments, pancreas and liver were rapidly excised for studying the histopathological change, electron microscope, immunohistochemistry and blood samples were taken from jugular vein for the quantitative determination of oral glucose tolerance test (OGTT) and serum insulin, C-peptide, fructosamine, lipid profile (Total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, vLDL-cholesterol) and free fatty acids (FFA) concentrations.
Livers were excised immediately after sacrifice and perfused with ice-cold saline and then homogenized. The homogenate was centrifuged and the supernatant was used for biochemical analysis of liver glucose-6-phosphatase (G-6-pase), liver glycogen content and glycogen phosphorylase. In addition, the homogenate was used for the measurement of liver and kidney oxidative stress and antioxidant defense markers lipid peroxidation (LPO), glutathione content (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities.
Moreover, visceral adipose tissue samples were taken for determination of mRNA expression levels of resistin and adiponectin at the molecular level using reverse transcriptase-polymerase chain reaction (RT-PCR).
In diabetic rats, glucose tolerance curve was elevated markedly and treatments with C. scolymus leaf and flower caused significant alleviation of the impaired glucose tolerance.
Serum insulin and C-peptide exhibited a similar behavioral pattern in vivo, since they were decreased in the NA-STZ diabetic rats and increased as a result of treatment diabetic rats with C. scolymus leaf and flower head extract. Serum fructosamine was markedly increased in diabetic rats and decreased after treatment with C. scolymus. Liver glycogen content was enormously decreased in the diabetic rats and increased as a result of treatment with C. scolymus.
Regarding the activities of liver glucose-6-phosphatase and glycogen phosphorylase, the recorded activities showed more or less a similar behavioral pattern, they were increased markedly in the diabetic rats and decreased by treatment with C. scolymus.
In STZ/ NA diabetic rats marked increases of serum triglycerides, total cholesterol, LDL-cholesterol, vLDL-cholesterol and FFA concentrations were observed, while the concentration of HDL-cholesterol was decreased. The treatment of diabetic rats with either C. scolymus leaf or flower head extract had profound ameliorative effects on the disrupted lipid profile.
C. scolymus leaf or flower head extracts decreased liver and kidney lipid peroxidation while increased glutathione content and antioxidant enzyme activities (SOD and GPx).
NA-STZ diabetic rats exhibited a highly significant decline in adipose tissue adeponectin mRNA expression level when compared to normal control rats and significant increase in adipose tissue resistin mRNA expression level when compared to normal control rats. Adeponectin mRNA expression of C. scolymus leaf or flower head extract treated rats was increased while resistin mRNA expression was significantly decreased.
The pancreas of C. scolymus leaf and flower head extract treated rats showed nearly normal structure of islets of Langerhans. Histopathological assessment of liver of C. scolymus leaf and flower treated rats showed amelioration of the microscopical structure of hepatocytes.
Immunohistochemistry in islets of Langerhans and liver of C. scolymus leaf and flower head extract treated rats showed reduced intensity of TNF-alpha. Immunohistochemistry in islets of Langerhans of C. scolymus leaf and flower head extract treated rats showed positive immunoreactions of β-cells for insulin granules that were obviously increased in numbers.
Ultrastructure of exocrine part pancreas of C. scolymus leaf and flower head extract showed marked improvement represented by increase in zymogen granules, regular contours of nuclei and flattened rough endoplasmic except few vacuoles. Ultrastructure of β-cell of C. scolymus leaf and flower head extract treated showed few vacuoles in β-cells and increase of secretory granules compared to the diabetic rats appeared nearly similar to the control group. Ultrastructure of hepatocytes of liver tissue of C. scolymus leaf and flower head extract showing normal nucleus and cover cell with their preserved structures.
In conclusion, the present study revealed that C. scolymus leaf and flower head extracts have both pancreatic (insulinotropic) and extra-pancreatic (insulin mimetic) effects. The treatment with C. scolymus leaf and flower head extracts were found to be beneficial on all aspects of disrupted metabolism of NA-STZ type 2 diabetic rats. Both agents were effective in improving the impaired glucose tolerance, increasing serum insulin and C-peptide concentrations, alleviation of the disrupted lipid profile, amelioration of the antioxidant status. In addition, they increased adipose tissue expression of adeponectin and decreased expression of resistin.