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

Abstract

Scutellaria baicalensis Georgi (Huangqin or Chinese Skullcap) has been used to treat inflammatory-related disorders in China and other Asian countries for centuries, and is a major ingredient of many traditional Chinese medicines. The main constituents of the root of Scutellaria, baicalin along with its aglycone, baicalein, are important components of some modern formulations. In bioavailability studies investigating baicalin, the authors found a substance, as a metabolite of baicalin in rabbit plasma, after oral administration of baicalin. Orally administered pure baicalin and the metabolite was detected in rabbit plasma using high-performance liquid chromatography, and the structure of the metabolite was elucidated using electrospray ionization mass spectrometry methods. is one of the most widely used traditional Chinese medicines (TCMs), and is officially listed in the Chinese pharmacopoeia (1). It has been used for dissipating heat, moistening aridity, purging fire, detoxifying toxicosis and anti-inflammation (2) expressed in the terms of TCM, as well as anti-cancer (3), anti-bacteria and anti-virus, antioxidant activities (4), reducing total cholesterol levels and decreasing blood pressure in the terms of modern medicine (5,6). Baicalin (baicalein 7-O-β-glucopyranuronoside [ Figure 1]) is a well-known bioactive component in the roots of S baicalensi. Baicalin can protect the myocardium from reperfusion-induced damage in isolated rat hearts via the antioxidant and paracrine (7), inhibit 3T3-L1 preadipocytes differentiation by down-regulation of PDK1/Akt phosphorylation (8), and attenuates brain edema in a rat model of intracerebral hemorrhage (9). Glucuronidation is the main metabolic pathway for baicalin (10,11). Five biliary metabolites have been identified after oral administration of baicalin to rats. The major same metabolites of baicalin in Scutellaria extract and Shuanghuanglian were baicalin-6-O-β-glucopyranuronoside-7-O-β-glucopyranuronoside, baicalin-6-O-glucoside-7-O-β-glucopyranuronoside and 6-O-methyl-baicalin -7-O-β-glucopyranuronoside, baicalin-6-O-β-glucopyranuronoside and baicalein (11). Three biliary metabolites have been identified after oral administration of baicalin to human. The major same metabolites of baicalin were baicalein-6-O-β-glucopyranuronosideβ6-O-methy-l baicalin-7-O-β-glucopyranuronoside and baicalin (12). 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. Baicalin (Batch No.111432-200807) and baicalein (Batch No.111595-200604) were purchased from the National Institute for the Control of Pharm...