Stereoselective pharmacokinetics and anti-inflammatory activity of amygdalin epimers: implications for thermal and pH stability in amygdalin-based functional foods

Abstract

Armeniacae semen amarum (ASA), the seed of Prunus armeniaca L., is widely consumed as both a food and a traditional medicinal ingredient, but thermal processing may induce epimerization of its key constituent, amygdalin (Amy), potentially altering its bioactivity and safety. Herein, we compared the two epimers, R-Amy and S-Amy, for anti-inflammatory activity, pharmacokinetics, and the stability of R-Amy under processing conditions. S-Amy was prepared via thermally induced epimerization of R-Amy followed by β-glucosidase-mediated stereoselective hydrolysis. In LPS-stimulated RAW264.7 macrophages, R-Amy showed superior anti-inflammatory activity to S-Amy, attributed to stronger suppression of the TLR-4/NF-κB/iNOS axis. Following oral administration in rats, both epimers underwent extensive metabolism in the gastrointestinal tract; notably, R-Amy showed 1.90-fold and 1.84-fold higher C_max and AUC_(0–t) than S-Amy, respectively. For the primary active metabolites R-prunasin (R-Pru) and S-prunasin (S-Pru) of Amy, the C_max, AUC_(0–t) and bioavailability (F) of R-Pru were 1.47-fold, 4.84-fold and 4.65-fold higher than those of S-Pru, respectively, indicating stereoselective absorption. Bidirectional epimerization between R-Amy and S-Amy was observed both in vivo and during thermal processing. Furthermore, we investigated the effects of compatibility materials with different physicochemical properties on the configurational stability of R-Amy during decoction. The results revealed that acidic conditions and specific food compatibilities significantly inhibited R-Amy epimerization, thereby preserving the more bioactive epimer, whereas alkaline conditions promoted its conversion. Collectively, these results reveal that processing-mediated control of Amy stereochemistry determines its metabolic disposition and biological activity, establishing a mechanistic rationale for enhancing ASA-based functional foods and therapeutics.