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International Journal of Pharmacology
Year: 2019  |  Volume: 15  |  Issue: 1  |  Page No.: 19 - 30

Comparative Pharmacokinetics and Metabolic Profile of Rhein Following Oral Administration of Niuhuang Shang Qing Tablets, Rhubarb and Rhein in Rats

Yu Zhang, Huiling Ma, Xi Mai, Zhaoxing Xu, Yongchao Yang, Huanlu Wang, Leiting Ouyang and Shuhao Liu    

Abstract: Background and Objective: Niuhuang Shang Qing tablet (NHSQ) is commonly used in traditional Chinese medicine preparation and rhein is a bioactive component in NHSQ for the anti-inflammatory effect. Up to now, there was no study done on pharmacokinetic (PK) of rhein after oral NHSQ and also no study on metabolic profile of rhein in vivo. The aim of this study was to investigate PKs of rhein, explore the reasons of PK differences after oral administration of NHSQ, rhubarb and rhein in rats, identify the metabolites of rhein in multi-biosamples and establish the metabolic profile of rhein. Materials and Methods: Male and female Sprague-Dawley rats were given NHSQ, rhubarb and rhein orally administration. Samples from the plasma were collected at different times for PK analysis and samples from plasma, urine and internal organs (brain, heart, liver and kidney) were collected for metabolic profile analysis. Results: The Cmax and AUC of rhein were significantly increased by rhein group, rhubarb group and NHSQ groups, the reason was that rhubarb, peppermint and chrysanthemum in NHSQ could produce additive, synergetic effects. Glucuronidation was the main metabolic pathway for rhein, followed by methylation and sulfation. Rhein and its metabolites distributed extensively in plasma, kidney, urine, liver and heart, anthrones could pass through blood-brain barrier more easily than anthraquinones. Conclusion: The NHSQ was superior to rhubarb or rhein in PKs by rhein-various ingredients synergistic interactions in NHSQ. Extensive metabolism of rhein occurred in rats.

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