Balicalin, the Predominant Flavone Glucuronide of Scutellariae Radix, is Absorbed from the Rat Gastrointestinal Tract as the Aglycone and Restored to its Original Form

Abstract

When baicalin was orally administered to conventional rats, it was detected in their plasma for 24 h after administration, but baicalein, the aglycone of baicalin, was not detected. However, when baicalin was given to germ-free rats, only a small amount of baicalin was detected in their plasma within 2 h after the administration, its AUC0-lim (the area under the concentration-time curve from 0 to last determination time) being 12.0% of that in conventional rats. Subsequently, a considerable amount (55.1 +/- 6.2%) of baicalin was recovered from the gastrointestinal tract even 4 h after administration. When baicalein was orally administered to conventional rats, however, baicalin appeared rapidly in their plasma at an AUC0-lim value similar to that obtained after oral administration of baicalin, despite the absence of baicalein in plasma. When intestinal absorption was evaluated by the rat jejunal loop method, baicalein was absorbed readily, but only traces of baicalin were absorbed. Moreover, in conventional rats a small amount (13.4 +/- 3.1%) of baicalin and an appreciable amount (21.9 +/- 3.4%) of baicalein were recovered from the gastrointestinal tract even 4 h after oral administration of baicalin, but only a small amount (3.93 +/- 1.43%) of baicalein was detected in the intestinal tract 1 h after administration of baicalein. Baicalin was transformed to baicalein readily by the rat gastric and caecal contents. When baicalin was administered orally to conventional rats, an appreciable amount of baicalein was recovered in their gastrointestinal tracts. Moreover, baicalein was efficiently conjugated to baicalin in rat intestinal and hepatic microsomes. These results indicate that baicalin itself is poorly absorbed from the rat gut, but is hydrolysed to baicalein by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body.

Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes

“…16 On the basis of the results of reported studies, 6,16 it is suggested that the enterohepatic recycling of BA played an important role in the absorption of BA through the gastrointestinal tract: Thus, BA itself was poorly absorbed from the rat gastrointestinal tract, where it was hydrolyzed to its aglycone moiety, namely baicalein, by intestinal bacteria; then the baicalein was absorbed rapidly and converted back to BA in the systemic circulation, resulting in the second absorption peak. 40 The plasma drug concentration-time data of BA was analyzed with a noncompartmental model, and the results of pharmacokinetic parameters are shown in Table 3. Significant differences in the pharmacokinetic parameters of BA were observed between BA-CMC and BA-LP.…”

Simultaneous Determination of Baicalein, Baicalin, Wogonin, and Wogonoside in Rat Plasma by LC-MS/MS for Studying the Pharmacokinetics of the Standardized Extract of Scutellariae Radix

“…Scutellariae flavonoids are reported to be extensively metabolized after being absorbed mainly in the form of aglycones from the gastrointestinal tract. 16 Accordingly, aglycones such as baicalein and wogonin are likely to exist in plasma at a lower concentration than glycones, possibly less than 0.1 μg/mL. This was mentioned as a possible reason why the aglycones could not be detected by the authors of the previous study.…”

A metabolite of baicalin detected in rabbit plasma using electrospray mass spectrometry after baicalin administration

“…Baicalein-6-O-β-glucopyranuronoside has been detected as a major metabolite besides baicalin in plasma after oral administration of baicalin to rats (13). The conjugated metabolites are readily hydrolyzed by the enzyme β-glucuronidase/sulfatase to free aglycone, and baicalin has been found to be absorbed from the gastrointestinal tract as its aglycone, which is restored to the baicalin parent drug by glucuronidation in the intestine and the liver in vivo (14). The present study investigated metabolites of baicalin in rabbit plasma.…”