الفهرس 
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Abstract
Diabetes mellitus type 2 (T2DM) is a chronic metabolic condition distinguished by persistent hyperglycemia and insulin insufficiency brought on by a confluence of hereditary and environmental variables. Cardiovascular disease (CVD) is a structural and functional heart condition brought on by diabetes. It is characteristic by alterations in oxidative stress, apoptosis, intracellular Ca2+ abnormalities, and mitochondrial function.
The present study aimed to assess the effect of quercetin on insulin resistance, oxidative stress, inflammations, and apoptosis in the cardiac tissues of obesogenic diet/alloxan induced T2DM rat model and to evaluate the therapeutic potential of quercetin alone and in combination with metformin.
The study was conducted on 40 male albino rats two months old average weight 100- 120 g. The rats were fed obesogenic diet for a period of 4 weeks then the rats were injected intraperitoneally (i.p.) with single dose of alloxan. After 2 days of alloxan injection to induce diabetes, the rats with fasting blood glucose level of ≥ 200 mg/dl as measured by Glucometer, were considered diabetic rats and selected for the study. Forty rats were classified into five groups, each group consist of 8 rats. group I (Control group): Healthy male rats that maintained under a normal diet and did not receive any type of treatment. group II (Diabetic group): Diabetic untreated male rats. group III: Diabetic rats that received quercetin i.p in a dose of 50mg/kg daily for four weeks. group IV: Diabetic rats which were received metformin orally in a dose of 200 mg/kg daily for four weeks, group V: Diabetic rats that were received a combination of quercetin i.p and metformin oral daily for four weeks.
After completing the period of treatment, Rats in all studied groups were fasted overnight, blood samples were obtained for serum analysis of glucose parameters, lipid profiles, liver and kidney functions. All animals were scarified under deep anesthesia with isoflurane. gene expression of Nrf2, NF-B, CASP3, and Bax were all investigated in the cardiac tissues.
According to the present findings, quercetin has anti-inflammatory, antihyperglycemic, and antiapoptotic properties that could be useful in the treatment of T2DM. Quercetin’s anti- diabetic effects in obesogenic diet/alloxan diabetic rats are evidenced by a significant decrease in fasting blood sugar, insulin resistance, total cholesterol (TC), and triglycerides (TG). Quercetin also has anti-inflammatory, antioxidants effects and antiapoptotic effects, as it significantly donwnregulated NF-B, significantly upregulated Nrf2, and significantly downregulated Bax and Casp3 gene expression respectively. The best results were observed in the combined group treated with quercetin and metformin.
from the above-mentioned discussion, it can be concluded that:
1. Quercetin is a potent glucose and lipid-lowering agent that has significance in the treatment of diabetes.
2. Quercetin exhibits anti-inflammatory and antioxidant effects mediated by significant downregulation of cardiac NF-κB and upregulation Nrf2 gene expression.
3. Quercetin exhibits anti- apoptotic effects mediated by significant downregulation of cardiac Bax and CASP3 gene expression.
4. The last results showed that combination of metformin and quercetin exhibits superior improvement in inflammatory, and apoptotic gene expression in cardiac tissues.
5. Quercetin may be used in conjunction with metformin as an adjuvant therapy to increase the effectiveness of the treatment.
6. More researches required to determine the precise mechanism of action of quercetin on the apoptotic pathway in T2DM.