Evaluation of antioxidant & antidiabetic activities of iridoid glycoside isolated from Stachytarpheta cayennensis (Rich) Vahl leaf extract : in vitro combined with molecular docking approach

Abstract

BACKGROUND : Stachytarpheta cayennensis is a medicinal plant widely used in the treatment of inflammations, ulcer, fever, pain, hepatic, renal disorders, syphilis, gonorrhoea, pain, diabetes, and hypertension. PURPOSE : This study aimed at investigating the antioxidant and antidiabetic potentials of the chemical constituents of Stachytarpheta cayennensis leaf and its solvent extracts using both in vitro and in silico methods METHODS : The crude methanolic extract of S. cayennensis and its solvents fractions were tested for the presence of secondary metabolites using standard methods while the total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays using the Folin-Ciocalteu's and aluminum chloride reagents respectively. Thereafter, the aqueous methanolic fraction was purified on column chromatography to give compound 1 which was characterised using spectroscopic techniques. The pure isolate and solvents fractions of the extract were then evaluated for antioxidant and antidiabetic properties. Furthermore, in silico antidiabetic activity of the isolated compound was established using Autodock. RESULTS : The phytochemical screening of the crude methanolic extract and the solvent fractions revealed the presence of terpenoids, flavonoids, tannins, alkaloids, glycosides, sterols and phenols. The highest TPC and TFC were observed in ethyl acetate fraction (117.88 ± 9.83 GAE mg/g and 869.16 ± 7.26 QUE mg/g) while n-hexane fraction had the lowest (69.73 ± 1.47 GAE mg/g and 139.19 ± 2.69 QUE mg/g). The aqueous methanolic fraction, fractionated on column chromatography led to the isolation of compound 1, an iridoid glycoside known as ipolamiide. The ethyl acetate fraction demonstrated the highest DPPH free radical scavenging antioxidant activity (IC50 of 25.78 ± 0.05 µg/mL) while n-hexane fraction exhibited the least (4.67 ± 0.06 µg/mL) respectively, while the isolated ipolamiide had IC50 value of 49.4 ± 2.18 µg/mL. The in vitro α-amylase and α-glucosidase inhibitory activity of ipolamiide expressed in IC50 were 0.041 ± 0.021 mg/mL and 0.129 ± 0.030 mg/mL respectively compared to the standard drug acarbose (0.0163 ± 0.001 mg/mL and 0.0735 ± 0.0223 mg/mL) for α-amylase and α-glucosidase respectively. The docking analysis showed that ipolamiide exhibited docking scores that were comparable to those of established antidiabetic drugs (rosiglitazone, acarbose, gliclazide, and metformin) when interacting with the selected protein targets. Remarkably, ipolamiide displayed the most favourable docking score of -7.1 when bound to the insulin-like growth factor 1 kinase target. The docking results were visualized using Discovery Studio, which unveiled key molecular interactions contributing to the docking scores. These interactions comprised hydrogen bonding, pi-alkyl interactions, alkyl interactions, charge attraction, salt bridge interactions, and halogen interactions. These findings highlight the promising potential of ipolamiide as a prospective antidiabetic drug candidate. CONCLUSION : The antioxidant and antidiabetic activities of extract and solvent fractions of S. cayennensis give credence to their traditional use as food and medicine. In addition, the in silico and in vitro antidiabetic assessment of ipolamiide obtained from the plant indicated that it may provide a lead for development of a new antidiabetic drugs in the near future.