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

Chia (Salvia hispanica) seeds (C) are known for their potential metabolic, dermatological, and neuroprotective benefits; however, a systemic chemometrics integration linking multi-origin omics-based phenolic profiling to enzyme inhibition potential is yet to be explored. Eleven (C1-C11) different origins of chia seeds were extracted with a green solvent of acetone: water (70:30 v/v) using an ultrasonic dismembrator and quantified for the major phenolic compounds using UHPC-DAD. The compounds were evaluated in five different enzyme models of α‑amylase (ALP), acetyl- and butyryl-cholinesterase (AChE, BChE), lipase (LPS), and tyrosinase (TYR) inhibition. The K-mean cluster analysis, one-way ANOVA, and PCA were used to identify significant correlations and mean differences. Among the phenolics, rosmairinic acid (RA) (385.77 ppm), chlorogenic acid (cGA) (86.33 ppm), and ferulic acid (FA) (40.51 ppm) were found the major constituents, whereas the highest phenolic accumulation was observed for USA (78.7 ppm), Saudi Arabia (69.2 ppm), and Ecuador (52.5 ppm) origins. The initial screening revealed inhibition of 38–71% against ALP, with the lowest IC₅₀ value of 104.4 μg/mL for the C4 (Indian origin). The screening for AChE inhibition ranged from 36–63%, highest in Mexico (C6) and the USA (C10); the lowest IC₅₀ value was noted for C10 (97.52 μg/mL). The range for BChE inhibition was 53–73%, with USA (C10) showing the strongest inhibition, even with the lowest IC₅₀ value (79.41 μg/mL). For LPS inhibition, the initial screening values ranged from 37–69%, highest for USA (C10) in preliminary screening and lowest during IC₅₀ determination (90.82 μg/mL). The TYR inhibition exhibited more activity for Ecuador (C2, 67%) and Peru-yellow (C7, 66%); however, the lowest IC₅₀ values observed were 88.81 μg/mL for C2 and 95.41 μg/mL for C7. The statistical analysis of K-mean, PCA, and ANOVA revealed astrong correlation for the phenolic content vs enzyme inhibition activity. In particular, RA, FA, cGA, and quercetin (QT) exhibited a strong inhibition profile for enzyme inhibition. The study successfully evaluated the origin-dependent variability for the phenolic composition of chia seed, resulting in variation in biological activity for the chia extracts.