Capparis spinosa (CS) is known as a hypoglycemic medication in many countries. This study was designed to reveal the protective effects of the hydro-ethanolic extract of CS (HECS) fruit against diabetes and oxidative stress in type 2 diabetic rats (T2D). T2D was induced in 4 groups of adult male Sprague Dawley rats, using high fat diet (HFD) and low dose of streptozotocin (STZ). The four groups of diabetic rats were orally gavaged with HECS (200 & 400 mg/kg), metformin (50 mg/kg) or vehicle for 28 days. Two non-diabetic groups were assigned as normal control and HECS treated ones (400 mg/kg). The glucose intolerance, HOMA-IR score, HbA1c level, antioxidative status and expression of genes involved in hepatic gluconeogenesis and lipogenesis were determined. Although HECS had no significant effect on decreasing of HOMA-IR score and HbA1c, it significantly decreased glucose intolerance as well as oxidative stress by reduction of hepatic lipid peroxidation and increase of antioxidant enzymes levels in diabetic rats. Also, HECS treated diabetic rats showed a significant enhanced dyslipidemia, increased weight gain and sera insulin level. In addition, HECS significantly decreased hepatic phosphoenolpyruvate carboxykinase (PEPCK), increased acetyl CoA carboxylase and non-significantly decreased hepatocyte nuclear factor-4α (HNF-4α) as a transactivator of PEPCK at mRNA expression level in diabetic rats. This study indicated the anti-oxidative and anti-diabetic effects of C. spinosa fruit extract and confirmed its traditional usage as a remedy for T2D.
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