In Vitro and In Silico Evaluation of Anticholinesterase and Antidiabetic Effects of Furanolabdanes and Other Constituents from Graptophyllum pictum (Linn.) Griffith

Graptophyllum pictum is a tropical plant noticeable for its variegated leaves and exploited for various medicinal purposes. In this study, seven compounds, including three furanolabdane diterpenoids, i.e., Hypopurin E, Hypopurin A and Hypopurin B, as well as with Lupeol, β-sitosterol 3-O-β-d-glucopyranoside, stigmasterol 3-O-β-d-glucopyranoside and a mixture of β-sitosterol and stigmasterol, were isolated from G. pictum, and their structures were deduced from ESI-TOF-MS, HR-ESI-TOF-MS, 1D and 2D NMR experiments. The compounds were evaluated for their anticholinesterase activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BchE), as well as their antidiabetic potential through inhibition of α-glucosidase and α-amylase. For AChE inhibition, no sample had IC50 within tested concentrations, though the most potent was Hypopurin A, which had a percentage inhibition of 40.18 ± 0.75%, compared to 85.91 ± 0.58% for galantamine, at 100 µg/mL. BChE was more susceptible to the leaves extract (IC(50) = 58.21 ± 0.65 µg/mL), stem extract (IC(50) = 67.05 ± 0.82 µg/mL), Hypopurin A (IC(50) = 58.00 ± 0.90 µg/mL), Hypopurin B (IC(50) = 67.05 ± 0.92 µg/mL) and Hypopurin E (IC(50) = 86.90 ± 0.76 µg/mL). In the antidiabetic assay, the furanolabdane diterpenoids, lupeol and the extracts had moderate to good activities. Against α-glucosidase, lupeol, Hypopurin E, Hypopurin A and Hypopurin B had appreciable activities but the leaves (IC(50) = 48.90 ± 0.17 µg/mL) and stem (IC(50) = 45.61 ± 0.56 µg/mL) extracts were more active than the pure compounds. In the α-amylase assay, stem extract (IC(50) = 64.47 ± 0.78 µg/mL), Hypopurin A (IC(50) = 60.68 ± 0.55 µg/mL) and Hypopurin B (IC(50) = 69.51 ± 1.30 µg/mL) had moderate activities compared to the standard acarbose (IC(50) = 32.25 ± 0.36 µg/mL). Molecular docking was performed to determine the binding modes and free binding energies of Hypopurin E, Hypopurin A and Hypopurin B in relation to the enzymes and decipher the structure–activity relationship. The results indicated that G. pictum and its compounds could, in general, be used in the development of therapies for Alzheimer’s disease and diabetes.