Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE:Rhein (Rh), baicalin (BG) and berberine (Be) are important coexisted constituents of San-Huang-Xie-Xin-Tang, which was widely used in traditional Chinese medicine for the treatment of gastritis, hypertension, gastric bleeding and peptic ulcers, etc. AIM OF THE STUDY:Based on the extensive phase II conjugation reactions of polyphenols (Rh and BG) in vivo, the aims of the present study were to investigate the effects of combination (Rh, BG and Be) on the system exposures of total Rh and BG involving the phase II conjugates metabolites and its possible mechanism. MATERIALS AND METHODS:A 3×3 Latin square single heavy design was used to investigate the pharmacokinetics influence of total Rh and BG after combination of Be by treating plasma samples with β-glucuronidase/sulfatase both in beagle dogs and Wistar rats. In vitro and in situ experiment models including in situ rat intestinal perfusion, Caco-2 cell monolayer transport and small intestinal flora incubation system were used to discuss the possible mechanism. RESULTS:The results of pharmacokinetic interactions showed that combination significantly reduced the system exposures of total Rh and BG. Compared with Rh or BG alone, the mean area under concentration-time curves (AUC(0-t)) of total Rh and BG reduced by 31% and 77% in beagle dog experiment. In Wistar rat experiment, the AUC(0-t) of total Rh and BG reduced by 22% and 21%. Subsequently, the results of in situ rat intestinal perfusion and small intestinal flora incubation system tests revealed that combination may decrease the absorption and metabolism of BG. However, combination could not affect the transport profile of BG across the Caco-2 cell. Moreover, combination did not affect the absorption or metabolism profile of Rh in all three in situ/in vitro experiments. CONCLUSIONS:It was deduced that the possible mechanism of the reduction of the system exposures of total Rh and BG was related to that combination decreased the metabolism of BG to B or the phase II conjugates of Rh/BG excreted from liver/bile duct to their free aglycones in vivo by inhibiting intestinal flora. The potent effects of combination on the phase II conjugates of Rh and B in pharmacokinetics, shown in this paper, indicated that more attention should be paid to the phase II conjugates metabolites of these polyphenols (undergo extensive phase II conjugation reactions in vivo) when applied herbal products composed of these coexist compounds.
journal_name
J Ethnopharmacoljournal_title
Journal of ethnopharmacologyauthors
Wang Z,Hu H,Chen F,Lan K,Wang Adoi
10.1016/j.jep.2012.11.008subject
Has Abstractpub_date
2013-01-30 00:00:00pages
442-9issue
2eissn
0378-8741issn
1872-7573pii
S0378-8741(12)00769-6journal_volume
145pub_type
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