| Summary: | Background: <i>Ephedra foeminea</i> is known in Jordan as Alanda and traditionally. It is used to treat respiratory symptoms such as asthma and skin rashes as an infusion in boiling water. The purpose of this study was to determine the antidiabetic property of <i>Ephedra foeminea</i> aqueous extract in streptozotocin-induced diabetic rats. Methods: The aqueous extract of <i>Ephedra foeminea</i> plant was used to determine the potential of its efficacy in the treatment of diabetes, and this extract was tested on diabetic rats as a model. The chemical composition of <i>Ephedra foeminea</i> aqueous extract was determined using liquid chromatography–mass spectrometry (LC-MS). Antioxidant activity was assessed using two classical assays (ABTS and DPPH). Results: The most abundant compounds in the <i>Ephedra foeminea</i> extract were limonene (6.3%), kaempferol (6.2%), stearic acid (5.9%), β-sitosterol (5.5%), thiamine (4.1%), riboflavin (3.1%), naringenin (2.8%), kaempferol-3-rhamnoside (2.3%), quercetin (2.2%), and ferulic acid (2.0%). The antioxidant activity of <i>Ephedra foeminea</i> aqueous extract was remarkable, as evidenced by radical scavenging capacities of 12.28 mg Trolox/g in ABTS and 72.8 mg GAE/g in DPPH. In comparison to control, induced diabetic rats treated with <i>Ephedra foeminea</i> extract showed significant improvement in blood glucose levels, lipid profile, liver, and kidney functions. Interleukin 1 and glutathione peroxidase levels in the spleen, pancreas, kidney, and liver of induced diabetic rats treated with <i>Ephedra foeminea</i> extract were significantly lower than in untreated diabetic rats. Conclusions: <i>Ephedra foeminea</i> aqueous extract appears to protect diabetic rats against oxidative stress and improve blood parameters. In addition, it has antioxidant properties that might be very beneficial medicinally.
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