Novel Anti-diabesity Peptide Alkaloids from Allophylus africanus P. Beauv

Aim: The aim of the study was to characterize and investigate the mechanism of action of anti-hyperglycemic and anti-hyperlipidemic constitutents of Allophylus africanus. Background: Allophylus africanus P. Beauv is a medicinal plant commonly used in sub-Sahara Africa for the treatment of metabolic disorders and infectious diseases. Objective: The objective of the study was to isolate and characterize anti-hyperglycemic and antihyperlipidemic chemical constituents from Allophylus africanus, and to investigate the mechanism of their enzymatic inhibitions. Methods: The chemical constituents were isolated using various column chromatographic techniques. The anti-hyperlipidemic and anti-hyperglycemic properties of the chemical constituents were investigated by measuring their inhibitory effects on porcine pancreatic lipase and α- glucosidase enzymes. Fluorescence quenching constants obtained from Stern−Volmer plots were used to determine the mechanisms of inhibitory action. Results: Twelve compounds, of which three were new peptide alkaloids, ethylamino asperphenamate (10), allophylane (11) and allophyline (12), were isolated. The new peptide alkaloids and asperphenamate (9) inhibited porcine pancreatic lipase in a dose-dependent manner with IC50 < 90 μM. Also, 9, 12, stigmasta-5, 22-dien-3-O-β-D-glucoside (3) and eudesmenol (5) inhibited α- glucosidase enzymes with IC50 < 165 μM, which was lower than that of standard drug, acarbose (432.16 ± 6.52 μM). From the Stern-Volmer plots, 9 and 10 indicated a static quenching, while 11 and 12 suggested the occurrence of both static and dynamic quenching mechanisms on porcine pancreatic lipase. On α-glucosidase, only 12 exhibited a concurrent static and dynamic quenching mechanism. Conclusion: The anti-diabesity compounds obtained from A. africanus established its potential for the treatment of metabolic disorders. Among the isolated compounds, three have been reported for the first time in nature while others have been reported for the first time in the plant.