Newly discovered coffee compounds outperform diabetes drug in lab tests

A team of researchers led by Minghua Qiu from the Kunming Institute of Botany of the Chinese Academy of Sciences published a paper in the journal Beverage Plant Research that demonstrated the previously unknown antidiabetic activity of coffee and expanded the understanding of it as a functional food.

Scientists have developed a three-step analytical approach to search for bioactive diterpene esters in roasted Coffea arabica beans. The technique allowed the detection of both abundant and extremely low amounts of compounds capable of inhibiting α-glucosidase activity, while reducing solvent consumption and analysis time. In the first step, the crude diterpene extract was separated into 19 fractions using silica gel chromatography. Each fraction was then analyzed by 1H-NMR and tested for its ability to inhibit α-glucosidase. Using cluster thermal analysis of NMR data, the researchers identified fractions Fr.9-Fr.13 as the most promising in terms of biological activity.

A detailed study of fraction Fr.9 using ^13C-DEPT-NMR revealed the presence of an aldehyde group, which confirmed the preliminary conclusions. After purification by semipreparative HPLC, three previously undescribed diterpene esters were isolated and named caffaldehydes A, B, and C. Their structures were determined based on one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry.

Although the three compounds differed in the type of fatty acids they contained—palmitic, stearic, and arachidic—they all showed significant α-glucosidase inhibition. The IC₅₀ values ​​(45.07, 24.40 and 17.50 µM) indicated higher activity compared to the comparator acarbose.

To detect additional trace compounds difficult to identify by individual NMR or HPLC methods, the researchers applied LC-MS/MS to the pooled fractions and constructed a molecular network using the GNPS and Cytoscape platforms. As a result, three more previously unknown diterpene esters were identified, structurally similar to AC caffaldehydes, but differing in the composition of fatty acids – margaric, octadecenoic and nonadecanoic. Checking existing databases confirmed their novelty.

Overall, the work showed that the integrated deduplication strategy is an effective tool for searching for structurally diverse and bioactive compounds in complex food matrices such as roasted coffee.

The findings open up the prospect of creating coffee-based functional foods or nutraceuticals that can help control glucose levels and have potential benefits in diabetes. In addition, the proposed approach can be applied to other complex foods to quickly identify health-promoting compounds. In the future, the researchers plan to study in more detail the biological effect of the detected diterpenes in trace amounts, as well as evaluate their safety and effectiveness in in vivo experiments.