Summary: | This study aimed to assess the antioxidant and antidiabetic properties of ethanolic phytoextracts of <i>Calamintha incana</i> (Sm.) Helder leaves. Initially, the chemical characterization of the phytocomplex was performed using high-performance liquid chromatography (HPLC)/mass spectrometry (MS). The cytotoxicity of the ethanolic extract was assessed using an MTT assay in HepG2 cells. Subsequently, antioxidant activity was evaluated using a DPPH test. Finally, enzymatic tests with α-amylase, α-glucosidase, pancreatic lipase, and dipeptidyl peptidase IV (DPP-IV) were performed to evaluate their effects on glucose metabolism. The chemical composition of the extract is p-linolenic acid (13.2%), myristic acid (12.1%), and p-cymene (10.5%). The extract demonstrated low toxicity, with none of the tested concentrations inducing 50% cell death. Furthermore, the ethanolic extract revealed potent antioxidant activity using DPPH (IC<sub>50</sub> was 35.9 ± 0.7 µg/mL) and reducing power capacity (IC<sub>50</sub> was 90.3 ± 0.8 µg/mL). Regarding the antidiabetic activity, the extract caused a significant inhibition of α-amylase, α-glucosidase (IC<sub>50</sub> 46.3 ± 0.2, 56.8 ± 0.1 μg/mL, respectively), weak inhibition of pancreatic lipase and no notable inhibition of dipeptidyl peptidase IV. In conclusion, <i>C. incana</i> has antioxidant and antidiabetic properties and appears to exert insulin-independent hypoglycemic action.
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