Tetrahydrobisbenzylisoquinoline alkaloids from Phaeanthus ophthalmicus inhibit target enzymes associated with type 2 diabetes and obesity

Joe Anthony H. Manzano Lloyd Christian J. Llames Allan Patrick G. Macabeo   

Open Access   

Published:  Aug 24, 2023

DOI: 10.7324/JAPS.2023.154518

Diabetes and obesity are metabolic comorbidities declared by WHO as epidemics. Owing to the purported pharmaceutical activities of plant-derived secondary metabolites, we assessed the inhibitory potentials of the Philippine native plant Phaeanthus ophthalmicus tetrahydrobisbenzylisoquinoline alkaloidal constituents tetrandrine (1) and limacusine (2) against enzymes implicated in type 2 diabetes (T2D) and obesity such as α-glucosidase, dipeptidyl peptidase-IV (DPP-IV), porcine pancreatic lipase (PPL), and human monoacylglycerol lipase (MAGL) using in vitro experiments and molecular docking. Both alkaloids 1 (IC50 = 2.29 μg/ml) and 2 (IC50 = 2.68 μg/ml) showed stronger inhibition against α-glucosidase compared to the drug control acarbose (IC50 = 4.12 μg/ml). Alkaloids 1 (IC50 = 4.92 μg/ml) and 2 (IC50 = 3.80 μg/ml) also exhibited better inhibitory activities against DPP-IV compared to the drug control sitagliptin (IC50 = 6.90 μg/ml). Molecular docking results revealed better binding propensities for both 1 and 2 onto the active pocket of α-glucosidase and DPP-IV compared to their respective control drugs. Meanwhile, alkaloid 2 showed better in vitro (IC50 = 0.70 μg/ml) and in silico inhibitory activity vs. PPL compared to orlistat. Both alkaloids 1 and 2 showed moderate bioactivity against MAGL. Both alkaloids were predicted to possess drug-likeness properties. Our present study suggests the potentials of the tetrahydrobisbenzylisoquinoline alkaloidal phytoconstituents tetrandrine (1) and limacusine (2) from P. ophthalmicus in developing new-generation prodrugs against T2D and obesity.

Keyword:     Phaeanthus ophthalmicus tetrandrine limacusine diabetes obesity molecular docking


Manzano JAHH, Llames LCJ, Macabeo APG. Tetrahydrobisbenzylisoquinoline alkaloids from Phaeanthus ophthalmicus inhibit target enzymes associated with type 2 diabetes and obesity. J Appl Pharm Sci. 2023. http://doi.org/10.7324/JAPS.2023.154518

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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