Inhibition of d-ribose-induced glycation of metalloprotein human myoglobin by bioactive quinones

The anti-glycation effects and mechanisms of eight quinone-related compounds, primarily sourced from medicinal and edible plants, were evaluated in this study. In vitro glycation experiments were conducted to study the structural perturbation induced by d -ribose on human myoglobin (HMb) in the presence of the tested compounds. Spectroscopic and electrophoretic analyses indicated that among the four benzoquinone-related substances, thymoquinone and its structurally closest analogue 2,5-dimethyl-1,4-benzoquinone, exhibited significant inhibitory effects on the d -ribose-induced glycation, thereby maintaining protein structural stability, reducing advanced glycation end products (AGEs) formation, and attenuating the covalent protein modification by d -ribose. In contrast, 1,4-benzoquinone and hydroquinone (a reduction product of 1,4-benzoquinone) promoted HMb denaturation through the Michael addition mechanism. Of the two naphthoquinones, juglone and plumbagin, showed anti-glycation effects, whereas the anthraquinones emodin and chrysophanol showed no significant effects. Nano-HPLC-MS/MS analysis further showed that thymoquinone was more effective in preventing glycation than juglone and plumbagin. This study investigates the mechanisms underlying glycation inhibition by quinones, revealing that the presence of dual β -substituted carbons on the benzoquinone ring is critical for stabilizing protein conformations and suppressing glycation. It provides a preliminary mechanistic basis and identifies candidate molecules for potential applications of quinones in retarding glycation, such as in managing diabetic complications or inhibiting glycation reactions during food processing.