Quercetin inhibits advanced glycation end product formation via chelating metal ions, trapping methylglyoxal, and trapping reactive oxygen species

Figures & data

Fig. 1. Effects of metal ions in glucose-BSA, ribose-BSA, and MGO-BSA mediated AGE formation.

Notes: Diethylenetriaminepentaacetic acid (DTPA) and aminoguanidine (AG) were used as positive controls for removal of metal ions and for inhibition of AGE formation, respectively. Bars represent mean ± standard deviation of triplicate values. Paired t-test: **p < 0.01, *p < 0.05, N.S. p = not significant).

Fig. 2. Inhibitory effects of polyphenols against glucose-BSA, ribose-BSA, and MGO-BSA mediated AGE formation.

Notes: (a) Glucose- or ribose-mediated AGE formation in the presence of each polyphenol (1–10). (b) MGO-mediated AGE formation in the presence of each polyphenol (1–14). The concentration of each compound was 100 μM. Bars represent mean ± standard deviation of triplicate values.

Table 1. ¹H and ¹³C NMR data of isolated 3,4-dihydroxybenzoic acid (15) in MeOH-d₄.

Position	^δC, type	^δH, (J in Hz)	HMBC
C=O	171.2, s
1	124.2, s
2	118.6, d	7.43, d, 1H (2.1)	3, 4, 6, C=O
3	146.8, s
4	152.2, s
5	116.6, d	6 6.80, d, 1H (8.1)	3, 4, 1
6	124.7, d	7.41, dd, 1H (8.1, 2.1)	2, 4, C=O

Fig. 3. Quantitative analysis of degradation product (15), MGO adducts (16, 17, 18) and quercetin (10).

Notes: (a) HPLC profiles of the samples originated from Condition A without MGO, Condition B with MGO, and Condition C with MGO under an argon atmosphere. Column conditions: Mightysil (4.6 × 250 mm, 5 μm), 10% mobile phase A (H₂O, 0.1% AcOH) and 90% mobile phase B (MeOH, 0.1% AcOH), 1.0 mL/min. Detection wavelength: 254 nm. (b) The relative yield of oxidative degradation product (15), di-MGO quercetin adduct (18), mono-MGO quercetin adducts (16 and 17), and reduction rate of quercetin (10) in MGO-mediated AGE formation under Condition A, Condition B or Condition C. The relative yield was calculated from each peak area value at 254 nm in HPLC.

Fig. 4. Proposed mechanism for the fate of quercetin (10) in MGO-mediated AGE formation under ambient air conditions.

Notes: *Mono-MGO adduct (17) is shown as a representative. Trapping of two equivalent of MGO by quercetin (10) followed by trapping of one equivalent of reactive oxygen species at C2 position of di-MGO adduct (18) to give 3,4-dihydroxy benzoic acid (15).

Fig. 5. Structure of mono-MGO adducts, 16 and 17.

Fig. 6. Structure determination of di-MGO adduct (18) and mono-MGO (17).

Notes: (a) Observed NMR chemical shifts of 18 (I) and chemical shifts calculated for hemiacetal (II) or hemiketal (III). Hemiketal can be formed from di-MGO adduct of quercetin proposed by Li et al. ¹⁰⁾ (b) Observed NMR chemical shifts of 17 (I) and chemical shifts calculated for two possible structures (II and III). ChemNMR was used for chemical shift calculations of ^1H and ^13C NMR in each structure on ChemDraw Ultra, ver. 12.0.3.1216 (CambridgeSoft Corp, Cambridge, MA, USA).

Li XL, Zheng T, Sang S, et al. Quercetin inhibits advanced glycation end product formation by trapping methylglyoxal and glyoxal. J Agric Food Chem. 2014;62:12152–12158.10.1021/jf504132x

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