Scavenging Glyoxal and Methylglyoxal by Synephrine Alone or in Combination with Neohesperidin at High Temperatures

Abstract

α-Dicarbonyl compounds, such as glyoxal (GO) and methylglyoxal (MGO), are a series of chemical hazards that exist in vivo and in vitro, posing a threat to human health. We aimed to explore the scavenging effects on GO/MGO by synephrine (SYN) alone or in combination with neohesperidin (NEO). First, through LC−MS/MS, we confirmed that both SYN and NEO could effectively remove GO and form GO adducts, while NEO could also clear MGO by forming MGO adducts, and its ability to clear MGO was stronger than that of GO. Second, a synergistic inhibitory effect on GO was found when SYN and NEO were used in combination by using the Chou−Talalay method; on the other hand, SYN could promote NEO to clear more MGO, although SYN could not capture MGO. Third, after synthesizing four GO/MGO-adducts (SYN-GO-1, SYN-GO-3, NEO-GO-7, and NEO-MGO-2) and identifying their structure through NMR, strict correlations between the GO/MGO-adducts and the GO/MGO-clearance rate were found when using SYN and NEO alone or in combination. Furthermore, it was inferred that the synergistic effect between SYN and NEO stems from their mutual promotion in capturing more GO by the quantitative analysis of the adducts in the combined model. Finally, a study was conducted on flowers of Citrus aurantium L. var. amara Engl. (FCAVA, an edible tea) rich in SYN and NEO, which could serve as an effective GO and MGO scavenger in the presence of both GO and MGO. Therefore, our study provided well-defined evidence that SYN and NEO, alone or in combination, could efficiently scavenge GO/MGO at high temperatures, whether in the pure form or located in FCAVA.

Scavenging Glyoxal and Methylglyoxal by Synephrine and Neohesperidin from Flowers of Citrus aurantium L. var. amara Engl. in Mice and Humans

“…In contrast, SYN had almost no scavenging effect on MGO (Figure B), and yet NEO could inhibit more than 90% of MGO by adding 5 mmol/L for 24 h (Figure D). These results of the inhibitory activities and their trends over time and concentration for the two compounds at 37 °C were in agreement with our previous data at high temperatures …”

“…As shown in Figure C, based on the actual proportion of two components in plants, SYN (100 mg/kg bw) and NEO (400 mg/kg bw) in combination were administered to mice, and the total content of GO-adducts of SYN in group C1 (SYN + NEO) increased by 21.75% compared with the single SYN group A1 (100 mg/kg bw), while the total content of GO-adducts of NEO and HES in mouse urine and feces in group C1 (SYN + NEO) increased by 36.74 and 12.51%, respectively, compared with the single NEO group B2 (400 mg/kg bw). The findings revealed that SYN or NEO could promote each other to capture more GO in vivo , which was consistent with our previous findings that SYN and NEO can synergistically clear GO under high-temperature conditions in vitro …”

“…It is available for the quality control of Zhiqiao (medicinal citrus), with a specified content ≥3.0% (w/w) . In addition to the antidiabetic, antiobesity, anti-inflammatory, and anticancer effects of NEO, our previous studies suggested the effects of SYN and NEO on GO/MGO under high temperatures . Further, as reported, Citrus fruit extract (Citrus reticulata × Citrus sinensis and C.…”

“…Due to the fact that SYN and NEO generally coexist in a variety of citrus fruits and plants, − and our previous studies have also shown the synergistic scavenging effect of SYN and NEO on GO/MGO at high temperatures in vitro , hence, we designed mouse experiments in which SYN and NEO were administrated in combination. The GO/MGO-adducts of SYN, NEO, and HES in mouse urine and fecal samples, such as mono-GO-SYN (SYN-GO-1 + SYN-GO-2 + SYN-GO-3), mono-GO-NEO (NEO-GO-2 + NEO-GO-3 + NEO-GO-4 + NEO-GO-5 + NEO-GO-7), di-GO-NEO (NEO-2GO-3), mono-GO-HES (HES-GO), di-GO-HES (HES-2GO), mono-MGO-NEO (NEO-MGO-1 + NEO-MGO-2), mono-MGO-HES (HES-MGO), and di-MGO-HES (HES-2MGO), were quantified using UHPLC-QQQ-MS/MS.…”

“…The same volume of PBS instead of SYN was used as the blank control group for each reaction. At each time point, the reactions were terminated by adding 10 μL of acetic acid, and then 1 mL of sample was taken for derivatization according to our previous method . The derivative mixtures were filtered with a 0.22 μm water filter membrane, and the remaining GO/MGO was determined using HPLC-DAD (Waters Arc HPLC system, MA, USA) based on our previous method …”