Rutin is a natural flavonol glycoside with diverse health-promoting properties through the bioactivities of quercetin, its aglycone. While widely distributed in the vegetables and fruits of human diet, rutin is either absent or inadequate in common animal feed ingredients. Rutin has been supplemented to dairy cows for performance enhancement, but its metabolic fate in vivo has not been determined. In this study, 100 mg/kg rutin was administered to 4 Holstein cows intraruminally, and the ruminal fluid, plasma, and urine samples collected before and after the rutin dosing were examined by both targeted and untargeted liquid chromatography-mass spectrometry-based metabolomic analysis. Targeted analysis of rumen fluid samples showed that rutin and quercetin were rapidly degraded in the rumen within 1 and 2 h of the dosing, respectively. Untargeted metabolomic analysis further identified 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-methylcatechol as the microbial metabolites of quercetin in the rumen, peaking at 2 h and 4 h, respectively, after rutin dosing. Interestingly, quercetin and DOPAC as well as their conjugates were hardly detectable in plasma samples. Instead, 4-methylcatechol sulfate was identified as the major metabolite of quercetin in plasma and urine. The high abundance of 4-methylcatechol sulfate in the 6-h plasma samples and its absence in the pre-3h urine samples indicated the high bioavailability and slow absorption of 4-methylcatechol. Metabolomic analysis further revealed that rutin administration decreased the levels of p-cresol sulfate and hippuric acid, two phenolic microbial metabolites, in plasma and urine, suggesting potential competitive inhibition between quercetin degradation and microbial metabolism of aromatic amino acids in the digestive tract of dairy cows. Overall, these observations define the in vivo metabolic route of rutin and quercetin and further indicate that 4-methylcatechol, a bioactive metabolite, might contribute to the reported bioactivities of rutin and quercetin in dairy cows.

Metabolic fates of intraruminal rutin in dairy cows

ACS Spring Meeting 2021

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