Evaluation of the Antihyperglycemic efficacy of the roots of Ferula orientalis L.: An in vitro to in vivo assessment

Decoctions of Ferula orientalis L. (Apiaceae), have been traditionally used to lower blood glucose levels (BGLs). After in vitro enzyme inhibition tests on the dichloromethane extracts of the roots (FOD) and the methanol extract of the roots (FOM), isolation studies were carried out on the FOD extract. The anti-hyperglycemic effects of the FOD extract and the pure compounds were studied in mice using the Oral Glucose Tolerance Test (OGTT) and streptozotocin (STZ)-induced diabetes mellitus (DM) models. Molecular docking studies were performed on potent compounds in the binding pockets of enzymes α-glucosidase and α-amylase. The isolations of 11 compounds were isolated from the FOD extract, which comprised teferidine (1), ferutinin (FT) (2), teferin (3), epoxy-jaeschkeanadiol-p-hydroxybenzoate (4), epoxy-jaeschkeanadiol-6-vanillate (5), tovarol-8-angelate (6), leucoferin (7), tovarol-8-p-hydroxybenzoate (8), tovarol-8-vanillate (9), 6-β-p-hydroxybenzoyloxy-germacra-1(10),4-diene (10), and chimgin (11). Compounds 2 and 8-11 exhibited a higher inhibitory activity on α-glucosidase. In the OGTT, pretreatment with the FOD extract or compound 2 did not alter the BGLs after administration of the glucose solution compared to the control. In the STZ-induced diabetic mice model, no significant difference in the BGLs was observed with the FOD extract (200 mg/kg) or compound 2 (100 mg/kg)-treated diabetic mice compared to the diabetic control mice. The experimental studies all showed that the F. orientalis extract had significant effects on the enzyme systems involved in DM, and it would be appropriate to plan further studies on possible problems of bioavailability of the compound FT and the FOD extract, inadequate dose, and duration of administration.