The research team, led by Aljawharah Alqathama of Umm Al-Qura University in Makkah and Rizwan Ahmad of Imam Abdulrahman Bin Faisal University in Dammam, Saudi Arabia, purchased eleven commercially available chia seed batches coded C1 through C11, representing origins that included Saudi Arabia, Ecuador, Bahrain, India, Argentina, Mexico, Peru (both yellow and brown varieties), Bolivia, the United States, and Spain. Rather than relying on harsh organic solvents, the team embraced green chemistry. They tested twelve solvent systems in an ultrasonic dismembrator probe, which uses cavitation bubbles to rupture plant cell walls and release their chemical cargo. The winning combination was acetone and water in a 70:30 ratio, which extracted roughly 168.4 parts per million of cumulative phenolics—about three times more than a 50:50 acetone-water mix and well above any ethanol-water blend.

The intermediate polarity of the acetone-water system proved ideal for simultaneously dissolving both moderately polar phenolic acids and more polar flavonoids, while ultrasonic cavitation enhanced mass transfer through the seed matrix. Using a fully validated UPLC-DAD method built on a C18 reverse-phase column with a formic acid mobile phase gradient, the researchers quantified five target phenolics: chlorogenic acid, rosmarinic acid, ferulic acid, quercetin, and kaempferol. Rosmarinic acid dominated at 385.77 ppm, followed by chlorogenic acid at 86.33 ppm and ferulic acid at 40.51 ppm, with kaempferol and quercetin present only in trace amounts. Geographical origin mattered enormously: seeds from the United States accumulated the highest total phenolics at 78.7 ppm, followed by Saudi Arabia at 69.2 ppm and Ecuador at 52.5 ppm.

With the chemistry mapped, the team turned to biology, screening every extract against five enzymes selected for their therapeutic relevance. Alpha-amylase, the carbohydrate-digesting enzyme targeted by the diabetes drug acarbose, was inhibited by 38 to 71 percent across origins in initial screening. The Indian origin sample, C4, proved the standout, achieving the lowest IC50 value of 104.4 micrograms per milliliter—remarkably close to acarbose’s own 78.82 micrograms per milliliter. Intriguingly, C4 did not have the highest total phenolic content. Instead, it carried elevated levels of ferulic acid and chlorogenic acid, both known competitive inhibitors of carbohydrate-digesting enzymes, suggesting that the composition of a seed’s phenolic cocktail matters more than its sheer quantity.

The cholinesterase results may be the most clinically provocative. Acetylcholinesterase inhibition ranged from 36 to 63 percent, with Mexican and American samples leading the field and posting IC50 values of 99.02 and 97.52 micrograms per milliliter respectively—both below the 100 micrograms per milliliter threshold the authors describe as having considerable therapeutic relevance. Butyrylcholinesterase inhibition was even more consistent, spanning 53 to 73 percent across all origins. The American sample C10 delivered the single strongest result of the entire study, an IC50 of 79.41 micrograms per milliliter against BChE. Because butyrylcholinesterase activity rises in the later stages of Alzheimer’s disease, dual cholinesterase inhibition is considered superior to targeting acetylcholinesterase alone, placing chia seeds in the same pharmacological neighborhood as rosemary and sage extracts rich in rosmarinic acid.

The American sample’s dominance extended to lipid metabolism. Pancreatic lipase, the enzyme targeted by the anti-obesity drug orlistat, was inhibited by 37 to 69 percent in preliminary screening, with C10 again posting the lowest IC50 at 90.82 micrograms per milliliter. Mexico and Spain followed closely. The authors attribute this activity to chlorogenic acid, rosmarinic acid, and quercetin, which are thought to block the catalytic serine residue of lipase and obstruct access to its hydrophobic binding pocket. The potency rivals previously reported values for green tea catechins and grape seed proanthocyanidins, positioning chia extracts as candidates for anti-obesity functional beverages and metabolic health supplements.

Tyrosinase, the copper-containing enzyme behind skin pigmentation and enzymatic browning in foods, told a different story. Here the Ecuadorian and yellow Peruvian samples shone, with inhibition of 67 and 66 percent and IC50 values of 88.81 and 95.41 micrograms per milliliter. The Ecuadorian sample’s high rosmarinic acid content of 42.70 ppm fits the known mechanism: phenolic acids chelate the copper ions at tyrosinase’s binuclear active site and compete with the L-DOPA substrate. Strikingly, the American sample that dominated every other assay failed to yield a measurable tyrosinase IC50, an inverse relationship the authors interpret as evidence that specific phenolic profiles confer selectivity toward particular enzymes rather than blanket inhibition.

To untangle these patterns, the team deployed a statistical arsenal of k-means clustering, one-way ANOVA with Tukey post-hoc tests, and principal component analysis. The clustering separated the eleven origins into distinct groups, with chlorogenic acid and quercetin emerging as powerful discriminators. ANOVA revealed that ferulic acid significantly influenced both alpha-amylase and tyrosinase inhibition, while chlorogenic acid showed a pronounced effect against acetylcholinesterase. Principal component analysis, interpreted cautiously as exploratory given the small dataset and low Kaiser-Meyer-Olkin value of 0.14, explained a cumulative 82 percent of variance across four components, with quercetin and rosmarinic acid loading strongly on the first component alongside a notable negative loading for acetylcholinesterase inhibition.

Why should geography shape a seed’s pharmacy so profoundly? The answer lies in plant secondary metabolism. Environmental variables such as soil composition, pH, irrigation, temperature, radiation, and altitude all feed into the phenylpropanoid pathway that manufactures phenolic compounds. Abiotic stresses, including water scarcity and elevated ultraviolet exposure, can stimulate this pathway as part of the plant’s defense arsenal, boosting phenolic accumulation. Post-harvest handling, particularly drying methods, can further degrade or preserve these fragile molecules. The result is that two genetically similar chia seeds, grown on different continents, can carry measurably different chemical fingerprints and, by extension, different biological activities.

The study’s implications ripple outward in several directions. For the functional food and nutraceutical industries, it suggests that origin-specific sourcing could become a quality control strategy: American chia for neuroprotective and anti-obesity formulations, Indian chia for glycemic control, Ecuadorian chia for cosmeceutical applications. The authors caution, however, that the chemometric trends are preliminary and that the multivariate modeling was constrained by the small sample size and incomplete IC50 coverage. They call for broader geographic sampling, molecular docking and enzyme kinetics studies to confirm binding specificity, investigation of the seed’s lipid fraction, and ultimately in vivo studies and clinical trials to translate these in vitro signals into therapeutic reality. Until then, the findings add a compelling new dimension to the chia story: the seed’s celebrated health benefits may be written not just in its genes, but in the soil, sun, and stress of the places where it grows.

Subject of Research: Origin-dependent phenolic profiling and multi-target enzyme inhibition of chia seed extracts

Article Title: Antidiabetic, antihyperlipidemic, and anticholinesterase enzymes inhibitory potential of green-extracted and UPLC-DAD-quantified chia (Salvia hispanica, Lamiaceae) seed phenolic compounds

Article References: Alqathama, A., & Ahmad, R. (2026). Antidiabetic, antihyperlipidemic, and anticholinesterase enzymes inhibitory potential of green-extracted and UPLC-DAD-quantified chia (Salvia hispanica, Lamiaceae) seed phenolic compounds. Plant Biosystems, 160(5), Article 251. https://doi.org/10.1007/s44473-026-00260-z

Image Credits: AI Generated

DOI: 10.1007/s44473-026-00260-z

Keywords: chia seeds, phenolic compounds, enzyme inhibition, alpha-amylase, cholinesterase, lipase, tyrosinase, UPLC-DAD, green extraction, chemometrics, functional foods, Alzheimer's disease