Comparative metabolomics analysis of unique yellow hawthorn (Crataegus pinnatifida) and red-skinned cultivars reveals a different polyphenol biosynthesis flux and antioxidative and antidiabetic potential

Objectives: This paper aims to investigate the polyphenol metabolite variation and bioactivities of different-colored hawthorn berries (Crataegus pinnatifida). Materials and Methods: Comparative metabolomics analysis between peel and flesh of yellow hawthorn 'Jinruyi' (JRY) and red-skinned ones was carried out by UPLC-MS/MS. Antioxidant activities and alpha-glucosidase inhibition capacity were also tested among different colored hawthorn samples. Results: A total of 453 polyphenols was characterized, among which phenolic acids and flavonoids were abundant, and were closely relevant to the antioxidant capacity of hawthorn fruits. Polyphenol profile showed accession-specific accumulation in peel or flesh of different colored hawthorn. The unique yellow hawthorn was found to have few anthocyanins but showed enhanced flux to synthesize flavones and flavonols, especially flavone C-glycosides and acylated flavonol glycosides. The specific acylation decoration included acetylation, p-coumaroylation, and malonylation. In addition, yellow hawthorn showed excellent alpha-glucosidase inhibitory effect, which might be associated with the high concentration of 8 polyphenols including 5 phenolic acids, 2 flavone C-glycosides, and an acylated flavonol glycoside, namely, quercetin-7-O-(6 ''-malonyl)glucoside. Such acylated flavonol showed the strongest correlation with the inhibition effect of hawthorn fruits on alpha-glucosidase, and was predicted to have the lowest binding energy with the enzyme according to molecular docking analysis, indicating its great potential as a strong alpha-glucosidase inhibitor and an important antidiabetic ingredient in yellow hawthorn. Conclusions: The acylated flavonol glycosides and C-glycosyl flavones might be chemotaxonomic markers differentiating varieties and bioactivities of yellow hawthorn from the traditional red-skinned ones. These findings complement the existing knowledge on the metabolite composition and nutritional properties of hawthorn fruits.