Pharmacokinetics of Five Alkaloids and their Metabolites in Normal and Diabetic Rats after Oral Administration of Rhizoma coptidis

Abstract

Rhizoma coptidis has been clinically used for a long time for the treatment of various diseases in China, such as hypertension, diabetes, and inflammation. Previous studies have shown that alkaloid components of Rhizoma coptidis extract could be extensively metabolized and the metabolites were also considered to be the therapeutic material basis. However, until now, pharmacokinetic studies of the in vivo metabolites have not been revealed yet. The aim of the present study was to characterize the pharmacokinetics and excretions of five main alkaloids (berberine, jatrorrhizine, palmatine, epiberberine, and coptisine) and their seven metabolites (berberrubine, demethyleneberberine, jatrorrhizine-3-O-β-D-glucuronide, thalifendine-10-O-β-D-glucuronide, berberrubine-9-O-β-D-glucuronide, demethyleneberberine-2-O-sulfate, and demethyleneberberine-2-O-β-D-glucuronide) in rats after oral administration of Rhizoma coptidis extract. Meanwhile, comparative pharmacokinetics and excretions of these analytes in diabetic model rats were also investigated, since Rhizoma coptidis is widely used for the treatment of diabetes. Our results showed that the in vivo existing forms of alkaloid components were phase II metabolites, highlighting the glucuronidation metabolic pathway. In diabetic model rats, the utilization of Rhizoma coptidis alkaloids was significantly increased and the biotransformation of berberine into berberrubine was significantly inhibited.

The colonic metabolism differences of main alkaloids in normal and colitis mice treated with Coptis chinensis Franch. and Sophora flavescens Ait. herbal pair using liquid chromatography‐high resolution mass spectrometry method combined with chemometrics

“…Given that the comparative study of CC‐SF bio‐disposition in normal and colitis mice is lacking, our results can build a solid foundation for future study on the material basis and mechanism of CC‐SF in the treatment of colitis. In our study, the results from PCA indicated that the metabolism in UC was clearly different from that of the physiological condition, and the metabolism at 6 h after a dose may reflect the real colonic metabolism profile, which was in line with the literature [26]. The cluster heatmap analysis was consistent with the PCA and separated normal groups from colitis groups.…”

Chemicolome and Metabolome Profiling of Xieriga-4 Decoction, A Traditional Mongolian Medicine, Using the UPLC-QTOF/MS Approach

“…It effectively reduces fasting plasma glucose, postprandial blood glucose, and glycosylated hemoglobin by participating in insulin resistance, anti-inflammatory, antioxidation, regulating lipid metabolism disorders and intestinal flora, and other methods. Berberine is mainly used in the treatment of type 2 diabetes, obesity, and metabolic diseases [ 21 – 27 ]. We detected berberine in plasma, feces, and biological samples, indicating that the prototype and metabolites of berberine are involved in the hypoglycemic mechanism.…”