Comparative Metabolism Study of Five Protoberberine Alkaloids in Liver Microsomes from Rat, Rhesus Monkey, and Human

Yan Li; Yanyan Zhou; Nan Si; Lingyu Han; Wei Ren; Shaokun Xin; Hongjie Wang; Ran Zuo; Xiaolu Wei; Jian Yang; Haiyu Zhao; Baolin Bian

doi:10.1055/s-0043-108249

Planta Medica, Inhaltsverzeichnis

Planta Med 2017; 83(16): 1281-1288
DOI: 10.1055/s-0043-108249

Pharmacokinetic Investigations

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Comparative Metabolism Study of Five Protoberberine Alkaloids in Liver Microsomes from Rat, Rhesus Monkey, and Human

Yan Li^*

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Yanyan Zhou^*

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Nan Si

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Lingyu Han

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Wei Ren

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Shaokun Xin

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

²Capital Medical University School of Traditional Chinese Medicine, Beijing, China

,

Hongjie Wang

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Ran Zuo

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

²Capital Medical University School of Traditional Chinese Medicine, Beijing, China

,

Xiaolu Wei

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Jian Yang

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Haiyu Zhao

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

,

Baolin Bian

¹Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

²Capital Medical University School of Traditional Chinese Medicine, Beijing, China

› Institutsangaben

Abstract

Protoberberine alkaloids including berberine, palmatine, jatrorrhizine, coptisine, and epiberberine are major components in many medicinal plants. They have been widely used for the treatment of cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. However, the metabolism of five protoberberine alkaloids among different species has not been clarified previously. In order to elaborate on the in vitro metabolism of them, a comparative analysis of their metabolic profile in rat, rhesus monkey, and human liver microsomes was carried out using ultrahigh-performance liquid chromatography coupled with a high-resolution linear trap quadrupole-Orbitrap mass spectrometer (UHPLC-electrospray ionization-Orbitrap MS) for the first time. Each metabolite was identified and semiquantified by its accurate mass data and peak area. Fifteen metabolites were characterized based on accurate MS/MS spectra and the proposed MS/MS fragmentation pathways including demethylation, hydroxylation, and methyl reduction. Among them, the content of berberine metabolites in human liver microsomes was similar with those in rhesus monkey liver microsomes, whereas berberine in rat liver microsomes showed no demethylation metabolites and the content of metabolites showed significant differences with that in human liver microsomes. On the contrary, the metabolism of palmatine in rat liver microsomes resembled that in human liver microsomes. The content of jatrorrhizine metabolites presented obvious differences in all species. The HR-ESI-MS/MS fragmentation behavior of protoberberine alkaloids and their metabolic profile in rat, rhesus monkey, and human liver microsomes were investigated for the first time. The results demonstrated that the biotransformation characteristics of protoberberine alkaloids among different species had similarities as well differences that would be beneficial for us to better understand the pharmacological activities of protoberberine alkaloids.

Key words

protoberberine - alkaloids - metabolic profile - liver microsomes - interspecies difference - UHPLC-HR-MS

Volltext

Referenzen

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