Phytochemical Investigation and Docking Study of Antidiabetic Compounds from The Methanol Extract of Ceiba pentandra (Bombacaceae)

The bioactivity-guided isolation of hypoglycemic compounds from the crude methanolic root extract of C. pentandra led to the structural characterization of ten known compounds. Five of these compounds aridanin (1), corosolic acid (2), α-amyrin (3), (E)-methylsuberenol (6), and octadecanoic acid (10) were isolated from this genus for the first time, along with other known compounds: two flavonoids (quercetin (4) and kaempferol (5)), and three sterols (β-sitosterol (7), and stigmasterol (8) mixture), and β-sitosterol glucoside (9)). By using spectroscopic and spectrometric experiments, the isolated compounds were fully characterized by comparing their data with those reported in the literature. In addition, the extract was found to have potent hypoglycemic activity with IC₅₀of 5.62 ± 0.25 and 5.36 ± 0.24 µM, respectively, for α-glucosidase and α-amylase, while the most active fraction displayed inhibition effects with IC₅₀ of 5.36 ± 0.24 and 5.20 ± 0.25 µM, respectively. Amongst the isolated compounds, kaempferol (5), and a mixture of β-sitosterol (7) and stigmasterol (8) were more active compared to acarbose (IC₅₀ of 5.47 ± 0.27 µM) and quercetin (IC₅₀ of 12.51 ± 0.13 µM) as the references. Moreover, kaempferol exhibited the strongest activity, which agrees with flavonoids biological properties. This observation was further explored by molecular docking studies, which suggested that kaempferol could bind favourably to the active sites of the target enzymes, supporting a potential competitive inhibition mechanism. This study contributed to enrich the chemistry of Ceiba plants with five known additional compounds (1, 2, 3, 6, and 10) and made Ceiba pentandra a promising source of antihypoglycemic compounds.