الفهرس 
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Abstract
The present study was aimed to develop a reliable model for insulin resistance by using high fructose diet (HFD) & investigate the effect of synthetic antidiabetic agent (metformin) in comparison with the active principle of some natural plants (cinnamaldehyde, costunolide and combination between them) through measuring some biochemical parameters and levels of pro-inflammatory cytokines (TNF-α and CRP), which can be affected in case of consumption of high fructose diet. Forty-eight healthy male albino rats were included in this study, and then randomly divided into two groups (control group and high fructose diet group), control group is composed of 8 rats and was fed with balanced diet and high fructose diet (60% fructose) is composed of 38 rats. Ten weeks is needed to induce insulin resistance by HFD. Rats were fed on HFD divided into 5 groups according to treatment, HFD only, HFD plus cinnamaldehyde, costunolide plus combination of cinnamaldehyde and costunolide and HFD plus metformin. After 4 weeks from beginning of treatment, body weight, fasting blood glucose levels, fasting insulin levels, HbA1c were measured and HOMA IR calculated as well as serum levels of serum lipid profile was estimated. In addition, lipid peroxidation markers, antioxidant levels and pro-inflammatory cytokines (TNF-α and CRP) were estimated. Levels of serum Creatinine, Urea, Uric acid SGPT, SGOT and albumin were estimated for study the safety of drugs used on renal, hepatic tissues respectively. All data were statistically analyzed by SPSS version 20.0 software. HFD group showed a significant effect on parameters that reflect metabolic syndrome incidence. where there was a significant increase in fasting blood glucose, HbA1c, insulin levels and HOMA-IR, triacylglycerol, total cholesterol, LDL, uric acid, MDA, NO when compared with control group while there was a significant decrease in HDL, GSH and SOD levels as compared with control group. While metformin treated group showed decrease in fasting blood glucose, HbA1cand HOMA-IR, triacylglycerol, total cholesterol and LDL, NO, MDA and TNF-αlevel. Furthermore, no difference in blood insulin levels when compared with control and the HFD treated group and there was a significant increase in HDL, GSH and SOD levels. Treatment with cinnamaldehyde, costunolide and combination of cinnamaldehyde and costunolide reduced fasting blood glucose, HbA1c and HOMA-IR, triacylglycerol, total cholesterol, LDL, NO, MDA, TNF-α and CRP. On the other hand, Cinnamaldehyde treated group showed significant increase in blood insulin levels when compared with control group and costunolide, combination of cinnamaldehyde and costunolide treated group showed no difference in blood insulin levels when compared with control and the HFD treated group. Three previous groups demonstrated a significant increase in HDL, GSH and SOD levels. Creatinine, Urea, Uric acid, SGPT and SGOT levels in active compounds of natural plants treated groups showed a significant decrease than HFD group. While metformin treated group showed no difference in creatinine and urea levels with HFD treated group but decrease level of uric acid when compared with HFD group. This study indicated that cinnamaldehyde, costunolide and combination of cinnamaldehyde and costunolide improved different aspects of metabolic syndrome beside their safety on hepatic and renal tissues and may be used in combination with commercial insulin sensitizers drugs.