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, beta-sitosterol 3-O-beta-D-glucopyranoside, stigmasterol 3-O-beta-D-glucopyranoside and a mixture of beta-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 alpha-glucosidase and alpha-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 mu g/mL. BChE was more susceptible to the leaves extract (IC50 = 58.21 +/- 0.65 mu g/mL), stem extract (IC50 = 67.05 +/- 0.82 mu g/mL), Hypopurin A (IC50 = 58.00 +/- 0.90 mu g/mL), Hypopurin B (IC50 = 67.05 +/- 0.92 mu g/mL) and Hypopurin E (IC50 = 86.90 +/- 0.76 mu g/mL). In the antidiabetic assay, the furanolabdane diterpenoids, lupeol and the extracts had moderate to good activities. Against alpha-glucosidase, lupeol, Hypopurin E, Hypopurin A and Hypopurin B had appreciable activities but the leaves (IC50 = 48.90 +/- 0.17 mu g/mL) and stem (IC50 = 45.61 +/- 0.56 mu g/mL) extracts were more active than the pure compounds. In the alpha-amylase assay, stem extract (IC50 = 64.47 +/- 0.78 mu g/mL), Hypopurin A (IC50 = 60.68 +/- 0.55 mu g/mL) and Hypopurin B (IC50 = 69.51 +/- 1.30 mu g/mL) had moderate activities compared to the standard acarbose (IC50 = 32.25 +/- 0.36 mu g/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.