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

Herbal medicines, including TCMs, are considered useful agents to treat various human diseases Peng et al. 2018 ). CR has a long history of being used as an important herbal medicine in Asian countries because of its reliable curative effects against various diseases. Nowadays, the most predominant traditional uses of CR have been confirmed by modern pharmacological research. So far, these investigations have reported that CR contains abundant isoquinoline alkaloids (especially berberine), which are also the active substances responsible for the pharmacological effects of this TCM. CR and berberine have a broad-spectrum antibacterial effect, manifesting as bacteriostasis at low concentrations and sterilization at high concentrations. This suggests that a combination of berberine or CR and conventional antibacterial drugs might exert a greater effect. Intensive research has indicated that CR has potential as a cardioprotective agent. In addition to reducing the incidence, it also protects the heart from MI/R injury. These properties are mainly attributed to berberine, coptisine, palmatine, epiberberine, jatrorrhizine and magnoflorine. Many studies have demonstrated modulation of the composition of the gut microbiota (enrichment of beneficial microbiota and inhibition of harmful microbiota) as one of the most important aspect for treating obesity, diabetes, and other metabolic disorders. As a natural compound with both anti-inflammatory and antitumor activities, berberine shows great potential in cancer treatment. However, the effects of berberine are not strong; therefore, structural modification of berberine is required. Moreover, CR containing various active components may be more effective than its single component berberine and could provide multiple therapeutic effects. There is a significant difference between the blood concentration and the tissue concentration. Therefore, to find a suitable pharmacokinetic marker for CR may be challenging but is necessary. Moreover, the pharmacokinetics of TCM should try to elucidate all the chemical components entering the body and their processes in the body (absorption, distribution, metabolism and excretion), with the aim of building a bridge between the complex chemical components and the systemic clinical effects, to reveal the underlying mechanism(s). Additionally, related target-organ toxicity evaluations are lacking. Thus, more work should be devoted to investigating the pharmacokinetics and features of CR and its active components, and further clinical studies are required to evaluate the potential curative effects and possible toxicities of CR and its active components toward the target organs. In addition, according to the current pharmacological research, berberine is not only the main active component but also the primary toxic component of CR. Consequently, it is crucial to develop a strategy to balance the pharmacological effects and toxicity of berberine. Besides, current reports on the original plants used to make CR, including C. chinensis, C. deltoidea and C. teeta, commonly focus on the chemical components and pharmacological effects of the roots because of their traditional use in TCM, and the other parts of the plants are often ignored and disposed of without pretreatment (Shen 2006) . However, some previous reports revealed that the leaves of the CR plants also contain berberine (Li et al. 2004; Liu T et al. 2010) . Therefore, further research is required to investigate th