Tissue Distribution, Excretion, and Metabolic Profile of Dihydromyricetin, a Flavonoid from Vine Tea (Ampelopsis grossedentata) after Oral Administration in Rats

Abstract

Dihydromyricetin (DMY), a flavanonol compound found as the most abundant and bioactive constituent in vine tea (Ampelopsis grossedentata), possesses numerous biological activities. In the present study, an HPLC-MS/MS method for the determination of DMY in tissues, urine, and feces was developed and applied to the tissue distribution and excretion study after oral administration in rats, and the metabolic profile of DMY was further investigated using UPLC-QTOF-MS. The results indicated that DMY could be distributed rapidly in various tissues and highly in the gastrointestinal tract. The elimination of DMY occurred rapidly as well, and most unconverted forms were excreted in feces. A total of eight metabolites were identified in urine and feces, while metabolites were barely found in plasma. The predicted metabolic pathways including reduction, dehydroxylation, methylation, glucuronidation, and sulfation were proposed. The present findings may provide the theoretical basis for evaluating the biological activities of DMY and will be helpful for its future development and application.

Uptake and Transport Mechanism of Dihydromyricetin Across Human Intestinal Caco‐2 Cells

“…Moreover, in the influx direction (AP‐BL), the DMY permeability (Papp (AP‐BL) = (0.83 ± 0.08) × 10 −6 cm/s) was seriously lower than that of propranolol (Papp (AP‐BL) = (41.9 ± 3.30) × 10 −6 cm/s), which is a passive transcellular marker (Chabane, Ahmad, Peluso, Muller, & Ubeaud, ), indicating DMY was poorly absorbed. DMY metabolites were not detected during the uptake study or the transport experiments using a minor modified UPLC‐QTOF‐MS method published in our previous study (Fan, Tong, & Dong, ).…”

Interactions of Dihydromyricetin, a Flavonoid from Vine Tea (Ampelopsis grossedentata) with Gut Microbiota

“…This UPLC‐QTOF‐MS/MS method for the identification of DMY metabolites in rat fecal microflora was developed based on our previous study (Fan et al., ). The mass errors between the measured and calculated values were in the range of ± 2 mDa, which demonstrated the high level of mass accuracy for the identification of metabolites.…”

“…Although DMY metabolites produced by human intestinal bacteria in vitro (Zhang et al., ) and detected in rat feces in vivo (Fan et al., ) were reported before, the influence of gut microbiota metabolism on the pharmacokinetics of DMY and the modulation of DMY on the gut microbiota composition have not been investigated yet. Taken the pharmacokinetic characteristics and broad‐spectrum antimicrobial activity of DMY into consideration, the study on the interactions of DMY with gut microbiota may provide important information with respect to the mechanism study and dosage form development of DMY.…”

“…Previously, the pharmacokinetics, tissue distribution, excretion, and metabolic profile of DMY were studied after oral administration (100 mg/kg) in rats (Fan et al., ; Tong et al., ). DMY could be rarely absorbed in the gastrointestinal tract (GI) and showed poor oral bioavailability (Tong et al., ).…”

“…The elimination of DMY occurred rapidly in all tissues, and it could be metabolized via methylation, reduction, dehydroxylation, glucuronidation, and sulfation pathways. It was noteworthy that the parent compound and metabolites of DMY were hardly detected in the plasma, whereas most of them were eliminated in feces (Fan et al., ). As we known, the GI is a unique route through which external substances enter the human body (Zhu, Xiong, & Liu, ), populated by the concentrations of up to 10 11 or 10 12 cells/g and consists of a complex microbial community called gut microbiota (Etxeberria et al., ).…”