Metabolic Interaction between Ammonia and Baicalein.

Ammonia is treated as a primary waste product of cellular metabolism and can contribute to the alteration of neurotransmission, oxidative stress, and cerebral edema and astrocyte swelling when its concentration in the brain is high. The objective of this study was to determine whether bioactive polyphenol baicalein had the capacity to trap ammonia and . Under conditions, baicalein rapidly reacted with ammonia to generate two monoaminated products and one diaminated product under different reaction times. These three major aminated products were purified from the reaction mixture, and their structures were characterized as 5-NH-baicalein, 6-NH-baicalein, and 5,6-di-NH-baicalein based on the analysis of their HR-MS and 1D- and 2D-NMR data. In mice, both 5-NH-baicalein and 6-NH-baicalein were detected in 24 h fecal and urine samples collected from mice treated with baicalein (200 mg/kg) through oral gavage, and 6-NH-baicalein was also detected in mouse plasma and brain samples collected at 0.5 h after baicalein treatment. Significant amounts of 6-NH-baicalein were detected in all mouse samples including feces, urine, plasma, and brain. The levels of 6-NH-baicalein in feces and urine were significantly higher than those of 5-NH-baicalein. Furthermore, the average level of 6-NH-baicalein was very close to that of baicalein (3.62 vs 3.77 ng/g) in mouse brain, suggesting it is possible that baicalein has the capacity to be absorbed rapidly into the circulation system and then cross the blood-brain barrier into the brain to detoxify ammonia in the blood and brain. In conclusion, this study confirmed that baicalein, a flavonoid with a -trihydroxyl structure on the A-ring, has the potential to detoxify ammonia and treat ammonia-associated chronic diseases.