Qingshan Zhang1, Gaowa Wang1, Xi Chen2, Zhiqiang Han3, Xiangmei Chen4, Risu Na1, Haburi Jin1, Ping Li1, Renbatu Bu5. 1. Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, 028000, People's Republic of China. 2. Department of Chinese Pharmacy, Beijing Friendship Hospital Affiliated to Capital University of Medical Sciences, Beijing, 100050, China. 3. Medical Institution Conducting Clinical Trials for Human Used Drug of Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, 028000, China. 4. Mongolian Medicine College of Pharmacy of Inner Mongolia University for the Nationalities, Tongliao, 028000, China. 5. Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, 028000, People's Republic of China. brbt9898@163.com.
Abstract
BACKGROUND AND OBJECTIVES: Rhizoma coptidis extract and its alkaloids were reported to exhibit various pharmacological activities. However, pharmacokinetics investigations indicated that the plasma concentrations of the alkaloids were too low to explain their systemic therapeutic actions. Thus, the metabolic profile of Rhizoma coptidis in humans is yet to be fully investigated and the present study aimed to investigate the metabolic profile of Rhizoma coptidis in human urine after oral administration of Rhizoma coptidis extract. METHODS: In this study, the metabolism of Rhizoma coptidis at a clinical dose (5 g/60 kg/day) was investigated using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry. RESULTS: Totally, 30 constituents including 7 prototypes, 5 sulfation metabolites and 18 glucuronide conjugates were elucidated and identified on the basis of the characteristics of their high-resolution precursor ions, product ions, and chromatographic retention times in human urine. Among the 7 prototypes, 3 prototypes (M20, M26 and M28) were identified definitely by comparing with standards. Based on the metabolites detected in human urine, a possible metabolic pathway of Rhizoma coptidis in vivo was proposed. CONCLUSIONS: The results demonstrated that the metabolic fate of Rhizoma coptidis mainly involved sulfation and glucuronidation in human urine and the glucuronide conjugate M14 (berberrubinen-9-O-glucuronide) might be a pharmacokinetic marker for Rhizoma coptidis alkaloids in humans. This study will be helpful to comprehensively understand the metabolic process of Rhizoma coptidis and how Rhizoma coptidis shows its pharmacological effects in humans.
BACKGROUND AND OBJECTIVES: Rhizoma coptidis extract and its alkaloids were reported to exhibit various pharmacological activities. However, pharmacokinetics investigations indicated that the plasma concentrations of the alkaloids were too low to explain their systemic therapeutic actions. Thus, the metabolic profile of Rhizoma coptidis in humans is yet to be fully investigated and the present study aimed to investigate the metabolic profile of Rhizoma coptidis in human urine after oral administration of Rhizoma coptidis extract. METHODS: In this study, the metabolism of Rhizoma coptidis at a clinical dose (5 g/60 kg/day) was investigated using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry. RESULTS: Totally, 30 constituents including 7 prototypes, 5 sulfation metabolites and 18 glucuronide conjugates were elucidated and identified on the basis of the characteristics of their high-resolution precursor ions, product ions, and chromatographic retention times in human urine. Among the 7 prototypes, 3 prototypes (M20, M26 and M28) were identified definitely by comparing with standards. Based on the metabolites detected in human urine, a possible metabolic pathway of Rhizoma coptidis in vivo was proposed. CONCLUSIONS: The results demonstrated that the metabolic fate of Rhizoma coptidis mainly involved sulfation and glucuronidation in human urine and the glucuronide conjugate M14 (berberrubinen-9-O-glucuronide) might be a pharmacokinetic marker for Rhizoma coptidis alkaloids in humans. This study will be helpful to comprehensively understand the metabolic process of Rhizoma coptidis and how Rhizoma coptidis shows its pharmacological effects in humans.
Authors: Thomas Friedemann; Benjamin Otto; Kristin Klätschke; Udo Schumacher; Yi Tao; Alexander Kai-Man Leung; Thomas Efferth; Sven Schröder Journal: J Ethnopharmacol Date: 2014-06-12 Impact factor: 4.360