Valorization of Agave potatorum byproducts as a source of volatile α-glucosidase inhibitors

Agave (Agave potatorum) leaves are an overlooked byproduct of mezcal production. They possess a wealth of secondary metabolites with potential antidiabetic activity. The present study investigated this by identifying volatile constituents associated with in vitro inhibition of α-glucosidase derived from bio-guided hexane fractions of A. potatorum Zucc. leaves. The process involved extraction followed by silica-gel column chromatography, along with bioautography and ultraviolet-visible (UV-visible) assays, using acarbose as the positive control. The two most promising bio-guided fractions were characterized using Attenuated Total Reflection Fourier-Transform Infrared (ATR-FTIR) spectroscopy, phytochemical screening, and gas chromatography-mass spectrometry (GC-MS). Their in silico properties were evaluated through absorption, distribution, metabolism, and excretion (ADME) analysis and molecular docking.

Two fractions exhibited higher α-glucosidase inhibitory activity with inhibitory concentration (IC₅₀) values significantly lower than that of acarbose; however, none of the fractions achieved 50% inhibition of α-amylase. The inhibitory activity may be attributed to unsaturated metabolites with terpenoid-like structures. Twenty-three volatile organic compounds (VOCs) were identified in these two fractions by GC-MS. Among the compounds potentially associated with inhibitory activity of α-glucosidase are dodecan-1-ol, 2,4-di-tert-butylphenol, tetradecane, and benzophenone. The in silico analysis indicated that the VOCs that were identified were not expected to accumulate in the human body, and molecular docking suggested that the inhibitory effects of the identified ligands may be mediated by hydrophobic interactions and hydrogen bonding.

This research supports the revalorization of agave byproducts as a viable source of secondary metabolites capable of influencing glucose absorption by α-glucosidase, which is a therapeutic target for addressing type 2 diabetes mellitus, the second leading cause of death worldwide. © 2026 Society of Chemical Industry.