Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology

Wang, Jin; Wang, Lin; Lou, Guan-Hua; Zeng, Hai-Rong; Hu, Ju; Huang, Qin-Wan; Peng, Wei; Yang, Xiang-Bo

Currently, pharmacokinetics research on CR has mainly focused on the protoberberine alkaloids. After oral intake, blood exposure and absolute bioavailability are extremely low. During absorption, 50% of berberine undergoes extensive first-pass elimination . Then, the absorbed alkaloids are quickly and widely distributed in tissues, such as the brain, intestine, stomach, pancreas, heart, kidney, liver, spleen, lung, testicles and uterus, among which the liver has the highest concentration (Ma et al. 2010) . Furthermore, the concentrations of the alkaloids in tissues are not only higher than those in circulation, but also are eliminated at a slower rate . Researchers have analysed metabolites from urine, feces, plasma, and intestinal flora and found that they mainly comprise the sulphate and glucuronide conjugates of the CR alkaloids or the Phase I metabolites of the alkaloids . In liver microsomes, cytochrome P450 isoenzymes (CYPs) play a major role. The intestinal flora also exerts significant effect on the enterohepatic circulation of the metabolites, which may be related to the multiple peaks phenomenon of the pharmacokinetics of the CR alkaloids (Zuo et al. 2006) . Berberine is usually excreted in urine and bile. Other studies showed, only 0.013% of berberine is eliminated directly in urine after oral administration (Yu et al. 2000) . The metabolites are mainly eliminated via urine , and aproportion of them are also eliminated through bile (Zuo et al. 2006) . However, in some pathological conditions, such as diabetes mellitus, PI-IBS (post-inflammation irritable bowel syndrome) and lipopolysaccharide-related diseases, the pharmacokinetic processes are altered. In 2008, Yu et al. showed a higher exposure of berberine, palmatine, coptisine, epiberberine and jatrorrhizine, with 170-330% increases in C max (maximum concentration) and 150-350% increases in AUC 0-24 (area under curve) in diabetic rats, after oral administration of CRE (1.3 g/ kg). Then, in 2010, they discovered that impairment of the function and expression of P-glycoprotein in the intestine partly contributed to the increased exposure of the five protoberberine alkaloids .