Abstract
Size-exclusion chromatography, in conjunction with electrospray ionization mass spectrometry, exemplifies a screening methodology to identify α-glucosidase inhibitors from natural extracts. This approach could be used to speed the time of targeting active principles from complex matrices, as a substitute for the established in vitro enzymatic assays which depend on spectrophotometric methods where disadvantages including sensitivity to turbidity and substance interferences—extract pigmentation, or absorption in the visible light region of tested samples—represent factors that affect the chromogenic screenings. Gel permeation through a spin size-exclusion column allowed separating high-affinity molecules bounded to α-glucosidase in solution. After acid hydrolysis of the enzyme-ligand complex, electrospray ionization mass spectrometry was used as a direct detector for the ligand. This affinity-directed fractionation was illustrated by using a crude extract, semi-purified fractions, and pure active glycolipids from moon vine seeds, Ipomoea alba L., Convolvulaceae, in addition to acarbose (positive control), which led to the identification of albinosides VI (ESI-MS m/z 991 [M + Na]+) and VII (ESI-MS m/z 975 [M + Na]+), two tracked high-affinity glycolipids, which demonstrated an in vitro inhibitory potential of α-glucosidases from yeast and rat intestine. Molecular docking predicted that these inhibitors bind to the enzyme catalytic site as acarbose.
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Acknowledgments
D.R.-R. is grateful to Consejo Nacional de Ciencia y Tecnología for his postdoctoral scholarship (CONACyT-Retenciones 2019-1, 205045). We thank Dr. Mabel Fragoso-Serrano (Facultad de Química) for assistance during the purification of the test compounds, M.Sc. Lucía del Carmen Márquez Alonso for support during the recording of mass spectra (Instituto de Química), and M.Sc. Cristian Fabián Salinas-Manzo for assistance during the gel permeation chromatography processes.
Funding
Funding was provided by Dirección General de Asuntos del Personal Académico, Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica, Universidad Nacional Autónoma de México (grants IN208019 and IG20021), and Dirección General de Servicios de Cómputo Académico (LANCAD-UNAM-DGTIC-204).
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DRR designed the study and performed and supervised the SEC-EM experiments, in vitro inhibitory enzymatic assays, and molecular docking, as well as elaborated the first draft of the manuscript. RPM guided the chemical analysis, contributed to the interpretation of all the results, and provided critical reading and insightful recommendations for the final manuscript. SER supervised the bioassays and molecular docking. RAE provided laboratory instrumentation and supplies. All of the authors have read the final manuscript and approved the submission.
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Rosas-Ramírez, D., Pereda-Miranda, R., Escandón-Rivera, S. et al. Identification of α-Glucosidase Inhibitors from Ipomoea alba by Affinity-Directed Fractionation-Mass Spectrometry. Rev. Bras. Farmacogn. 30, 336–345 (2020). https://doi.org/10.1007/s43450-020-00068-8
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DOI: https://doi.org/10.1007/s43450-020-00068-8