Metabolism and Pharmacokinetics of San-Huang-Xie-Xin-Tang, a Polyphenol-Rich Chinese Medicine Formula, in Rats and Ex-Vivo Antioxidant Activity

San-Huang-Xie-Xin-Tang (SHXXT), a widely used Chinese herbal formula, consists of rhizomes of Rheum officinale, roots of Scutellaria baicalensis and rhizomes of Coptis chinesis. This study investigated the metabolism and pharmacokinetics of polyphenols in SHXXT, including baicalin, baicalein, wogonin, emodin, aloe-emodin, rhein and chrysophanol. The quantitation methods of SHXXT decoction and rat serum using high performance liquid chromatography were developed and validated in this study. After oral administration of SHXXT decoction to rats, the parent forms of various constituents and their conjugated metabolites in serum were determined before and after hydrolysis with β-glucuronidase and sulfatase. The results showed that only free form of rhein can be quantitated, whereas the parent forms of coptisine, palmatine, berberine, baicalein, wogonin, emodin, aloe-emodin and chrysophanol were not detected in serum. The glucuronides of baicalein, wogonin, emodin, aloe-emodin, rhein and chrysophanol were the predominant forms in bloodstream. In order to evaluate the in vivo antioxidant activity of SHXXT, the serum metabolite of SHXXT was prepared, characterized and followed by evaluation of the effect on AAPH-induced hemolysis. The results indicated that metabolites of SHXXT exhibited significant free radical scavenging activity. We suggest that biologists redirect their focus to the bioactivity of the conjugated metabolites of these polyphenols

Metabolism and Pharmacokinetics of San-Huang-Xie-Xin-Tang, a Polyphenol-Rich Chinese Medicine Formula, in Rats and Ex-Vivo Antioxidant Activity

San-Huang-Xie-Xin-Tang (SHXXT), a widely used Chinese herbal formula, consists of rhizomes of Rheum officinale, roots of Scutellaria baicalensis and rhizomes of Coptis chinesis. This study investigated the metabolism and pharmacokinetics of polyphenols in SHXXT, including baicalin, baicalein, wogonin, emodin, aloe-emodin, rhein and chrysophanol. The quantitation methods of SHXXT decoction and rat serum using high performance liquid chromatography were developed and validated in this study. After oral administration of SHXXT decoction to rats, the parent forms of various constituents and their conjugated metabolites in serum were determined before and after hydrolysis with β-glucuronidase and sulfatase. The results showed that only free form of rhein can be quantitated, whereas the parent forms of coptisine, palmatine, berberine, baicalein, wogonin, emodin, aloe-emodin and chrysophanol were not detected in serum. The glucuronides of baicalein, wogonin, emodin, aloe-emodin, rhein and chrysophanol were the predominant forms in bloodstream. In order to evaluate the in vivo antioxidant activity of SHXXT, the serum metabolite of SHXXT was prepared, characterized and followed by evaluation of the effect on AAPH-induced hemolysis. The results indicated that metabolites of SHXXT exhibited significant free radical scavenging activity. We suggest that biologists redirect their focus to the bioactivity of the conjugated metabolites of these polyphenols

Pharmacokinetics and Relative Bioavailability of Flavonoids between Two Dosage Forms of Gegen-Qinlian-Tang in Rats

Gegen-Qinlian-Tang (GQT), a popular Chinese medicine prescription, consists of Puerariae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix. This study investigated the pharmacokinetics of GQT in rats and compared the bioavailability between two dosage forms, that is, traditional decoction (TD) and concentrated powder (CP). Rats were given TD and CP of GQT in a crossover design, and blood samples were withdrawn at predetermined time points. The quantitation methods of ten constituents in two dosage forms of GQT and in serum specimen using HPLC were developed and validated in this study. The pharmacokinetic parameters were calculated using noncompartment model. The results showed that daidzein, baicalein, wogonin, berberine, palmatine, and coptisine were not found in the circulation, whereas the sulfates/glucuronides of daidzein, baicalein, and wogonin were the major forms after oral administration of GQT. Comparison between two dosage forms indicated that the AUC0–t of daidzein sulfates/glucuronides after administration of CP was significantly lower than that of TD by 28.9%, whereas the bioavailabilities of baicalin/baicalein and wogonoside/wogonin were comparable between two dosage forms. In conclusion, the major flavonoids of GQT were extensively metabolized into sulfates/glucuronides and present as the major molecules in the circulation. TD of GQT revealed higher bioavailability of daidzin/daidzein than CP

Mutation in Enterovirus 71 Capsid Protein VP1 Confers Resistance to the Inhibitory Effects of Pyridyl Imidazolidinone

Enterovirus 71 is one of the most important pathogens in the family of Picornaviridae that can cause severe complications in the postpoliovirus era, such as encephalitis, pulmonary edema, and even death. Pyridyl imidazolidinone is a novel class of potent and selective human enterovirus 71 inhibitor. Pyridyl imidazolidinone was identified by using computer-assisted drug design. This virologic investigation demonstrates that BPR0Z-194, one of the pyridyl imidazolidinones, targets enterovirus 71 capsid protein VP1. Time course experiments revealed that BPR0Z-194 effectively inhibited virus replication in the early stages, implying that the compound can inhibit viral adsorption and/or viral RNA uncoating. BPR0Z-194 was used to select and characterize the drug-resistant viruses. Sequence analysis of the VP1 region showed that the resistant variants differed consistently by seven amino acids in VP1 region from their parental drug-sensitive strains. Site-directed mutagenesis of enterovirus 71 infectious cDNA revealed that a single amino acid alteration at the position 192 of VP1 can confer resistance to the inhibitory effects of BPR0Z-194