الفهرس 
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Abstract
Diabetes mellitus is a complex metabolic condition characterized by persistent hyperglycemia caused by decreased insulin action, secretion, or both, and is classified into two types: type 1 and type 2. Type 2 diabetes accounts for more than 90% of all diabetes cases and is linked to lipid and carbohydrate metabolic abnormalities. In diabetic patients, effective hyperglycemia control is crucial for minimizing the risk of micro- and macrovascular disease. Diabetes is mostly treated with exercise, diet, insulin, and the use of oral hypoglycemic medications. In addition to being costly, currently available synthetic anti-diabetic medications have considerable side effects and must be used on a daily basis.
Ginger is one of the most popular spices in the world. It has a long history of use as an herbal medication to treat a wide range of diseases such as vomiting, indigestion, pain, and cold-induced disorders. Ginger has anti-inflammatory properties via multiple mechanisms.
The present study aimed to evaluate the effect of Ginger extract on inflammations and insulin resistance in obesogenic diet/alloxan induced type 2 diabetic rat model and to evaluate the therapeutic potential of metformin alone and in combination with ginger extract. Also, to explore the possible molecular target of ginger extract alone and the combination of ginger extract with metformin.
The study was conducted on 40 male albino rats 2 months old and weighting from 100-150 g. The rats were prepared by feeding with obesogenic diet for 4 weeks and diabetes was induced by intraperitoneal (i.p.) injection with a single dose of alloxan (200 mg/kg) dissolved in distilled water, the rats were divided into two groups; group I (control group) consists of 8 healthy male rats that were fed a normal diet without any treatment, group II (diabetic group) consists of 32 diabetic rats that were subdivided into 4 sub-groups (eight rats each):Untreated group (IIA): diabetic rats weren`t receive any type of treatment, metformin treated group (IIB): diabetic rats were orally treated with metformin at a dose of 200 mg/kg BW/day for four weeks, treated group with ginger extract (IIC): diabetic rats were orally treated with ginger extract at a dose of 500 mg/kg BW/day for four weeks and the group treated with a combination of metformin and ginger extract (IID): diabetic rats were treated with metformin (200 mg/kg BW/day) and ginger extract (500 mg/kg BW /day) for four weeks.
At the end of four weeks, rats in all studied groups were overnight fasting, blood samples were collected for determination of FBG, Insulin, HOMA-IR, TG, TC, LDL-C and HDL-C, then all rats were sacrificed and liver tissues were dissected out for the determination of MDA content, NO content, TAC by FRAP, gene expression of NF-κB, INOS, COX-2, PTP 1B and miR-29a.
Our study indicates that metformin and ginger extract exhibit a dual action as anti-inflammatory and anti-hyperglycemic effect. The anti-diabetic effects in the obesogenic diet /alloxan diabetic rats are evidenced by significant decline in the FBG, HOMA-IR, TG, TC, LDL-C, ALT and AST levels. And the anti-inflammatory effects, as it significantly declines the MDA contents, NO contents, gene expression of NF-κB, INOS, COX-2 which leads to improve insulin sensitivity though significantly decline the gene expression of both PTP-1B and miR-29a and increase the TAC content.
Ginger extract which is prepared by maceration for 2 weeks in 95 % ethanol exhibits an anti-diabetic and anti-inflammatory effect and this may be due to the existence of Diacetoxy-6-gingerdiol in the extract which was found to be the most important variable correlating to the anti-diabetic and anti-inflammatory activity, so this needs further investigations.
from our results, we can conclude that:
1) The antiglycating and anti-diabetic/hypoglycemic properties of ginger might provide a viable approach through a significant decrease in FBG level.
2) Ginger boosts the antioxidant status through lowering MDA level, NO content, iNOS expression and increasing the TAC content.
3) Ginger extract improved lipid profile and antioxidant status through significant decreased of TC, TG, LDL-C and significant increased of HDL-C.
4) Ginger exerts anti-inflammatory actions by suppressing NF-κB cascade pathway.
5) Ginger improves insulin signaling pathways by suppression the gene expression of PTP1B and miR-29a.
6) Ginger extract produces anti-diabetic and anti-inflammatory effects nearly equivalent to metformin.
7) The combined group which was treated with ginger extract and metformin showed the best effect.
8) Ginger can be used in conjunction with metformin as an adjuvant therapy to increase the efficacy for the treatment of type-2 DM and to low the side effects of anti-diabetic drugs (metformin).