Identification of the toxic constituents in Rhizoma Coptidis

Increased Systemic Exposure to Rhizoma Coptidis Alkaloids in Lipopolysaccharide-Pretreated Rats Attributable to Enhanced Intestinal Absorption

“…Certain classic works of traditional Chinese medicine, such as Ben Cao Yan Yi (Augmented Materia Medica; Kou, 1997), have stated that, although rhizoma coptidis extract is an excellent therapeutic agent for dysentery, the dosage should be adjusted on the basis of the severity of the disease; otherwise, the health of the patient might be endangered. Berberine, the main toxic constituent of the rhizoma coptidis extract (Ma et al, 2010), has caused respiratory failure, extrapyramidal system reactions, severe arrhythmia, liver function injury, and even death in clinics in China (Li et al, 2008). These reports strongly suggested that rhizoma coptidis extract and its alkaloids not only are curative but also are potentially toxic and should be used carefully in clinics, especially in LPS-related inflammatory diseases.…”

“…The rhizoma coptidis extract was prepared by using standardized procedures, according to a previously reported method (Ma et al, 2010). The yield was 37.1%.…”

“…Likewise, berberine exhibits extremely low plasma concentrations after oral administration (Zuo et al, 2006;Liu et al, 2009). Researchers have proposed the following mechanisms for the low plasma concentrations of these alkaloids: 1) the alkaloids are metabolized in the intestine ; 2) absorbed alkaloids are pumped out by intestinal (Zhang et al, 2011) or hepatic (Tsai and Tsai, 2004) P-glycoprotein (P-gp); 3) absorbed alkaloids are metabolized quickly and extensively after absorption (Tsai and Tsai, 2004;Zuo et al, 2006;Yang et al, 2010); and 4) absorbed alkaloids are distributed widely in tissues Ma et al, 2010). The low plasma concentrations of the alkaloids are insufficient indicators of their in vivo bioactivities.…”

“…The low plasma concentrations of the alkaloids are insufficient indicators of their in vivo bioactivities. The alkaloids may produce their systemic therapeutic actions by modulating effectors in the gut (Lu et al, 2009), through generated metabolites that are both abundant (Zuo et al, 2006) and active (Li et al, 2011), or on the basis of the relatively dominant tissue distribution of the alkaloids themselves Ma et al, 2010). However, all of the aforementioned pharma-cokinetic studies were performed with normal subjects and experimental animals, and less is known about systemic exposure to rhizoma coptidis alkaloids in pathological cases, except for diabetic rats (Yu et al, 2010).…”

In vitro metabolic study of Rhizoma coptidis extract using liver microsomes immobilized on magnetic nanoparticles

“…In in vivo studies, experimental animals such as rats and rabbits are usually used and herbal extracts are given by oral administration. Metabolites enriched from sample matrices such as urine, plasma, and tissues are then analyzed and identified by means of high-performance liquid chromatography (HPLC)-mass spectrometry (MS), HPLC-NMR spectroscopy, gas chromatography-MS, and/or multidimensional liquid chromatography [8][9][10][11]. On the other hand, in vitro metabolic studies, owing to their good repeatability and easiness to perform, serve as an important alternative means of understanding drug metabolism and are widely used.…”