Phytochemical characterization and antidiabetic potential of Carum carvi L. seeds from Beni Mellal-Khenifra: in vitro, in vivo, in silico and ADME investigations

Abstract

This study aimed to analyze the phytochemistry of the aqueous extract of Carum carvi L. seeds (AECCS) from the Beni Mellal-Khenifra region and assess its antihyperglycemic activity and safety. The quantitative phytochemical analysis showed that the studied extract contains 0.27 ± 0.08 mg QE/mg DM and 0.57 ± 0.07 mg GAE/mg DM of flavonoids and polyphenols, respectively. Phytochemical analysis revealed 11 compounds, the most abundant being syringic acid (40.02%), cinnamic acid (26.54%), and 4-hydroxybenzoic acid (10.22%). The aqueous extract showed a significant antihyperglycemic effect in normal Albino mice at 60 min (p < 0.01; 2.15 ± 1.01 g/L) and 90 min (p < 0.05; 1.36 ± 0.52 g/L) after administration of the extract, as well as an inhibitory effect on the enzymatic activity of α-amylase, with an IC50 mg/mL (0.139 ± 0.023 mg/mL) in vitro. Furthermore, it significantly (p < 0.001) reduced postprandial hyperglycemia at 60 min (1.35 ± 0.27 g/L) and at 90 min (1.13 ± 0.17 g/L) in vivo. The extract also showed an inhibitory effect on α-glucosidase activity, with an IC50 of 56.66 ± 1.247 µg/mL in vitro, and it non-significantly reduced postprandial hyperglycemia at 90 min (1.14 ± 0.13 g/L) and 150 min (0.88 ± 0.07 g/L) in vivo. In addition to this pharmacological effect, the aqueous extract produced no hypoglycemic effects on basal blood glucose levels in albino mice and showed no signs of short-term toxicity. Molecular docking revealed that the bioactive compounds from the extract interacted differently with α-amylase and-α-glucosidase. Among them, catechin stands out with an affinity of -7.9 kcal/mol for α-amylase and − 6.9 kcal/mol for α-glucosidase. These compounds comply with Lipinski’s criteria, thus enhancing their potential for drug development. They fall into the mild toxicity category, ranging from moderate to low, with LD₅₀ values between 1034 and 10,000 mg/kg, indicating a good safety margin. Based on these results, which confirm the efficacy of this plant in traditional medicine for the treatment of diabetes, this plant could be used to treat diabetic patients.