Protective role of Coptidis Rhizoma alkaloids against peroxynitrite-induced damage to renal tubular epithelial cells

Abstract

A study was conducted to elucidate and compare the protective activity of alkaloids from Coptidis Rhizoma (berberine, coptisine, palmatine, epiberberine, jatrorhizine, groenlandicine and magnoflorine) using an LLC-PK1 cell under peroxynitrite (ONOO−) generation model. Treatment with 3-morpholino-sydnonimine (SIN-1) led to an increase in cellular ONOO− generation in comparison with non-treated cells. However, Coptidis Rhizoma extract and its alkaloids, except for berberine, reduced the cellular ONOO− level. In addition, DNA fragmentation induced by SIN-1 was significantly decreased by the extract, and also by coptisine, epiberberine, jatrorhizine, groenlandicine and magnoflorine. Moreover, treatment with berberine, coptisine, palmatine and epiberberine exerted a protective effect against G0/G1 phase arrest of cell cycle induced by SIN-1. The increase in cellular ONOO− generation, DNA damage and disturbance of the cell cycle by SIN-1 resulted in a decrease in cell viability. However, Coptidis Rhizoma extract, epiberberine, jatrorhizine, groenlandicine and magnoflorine significantly increased cell viability even at a concentration as low as 10μg mL−1. These findings demonstrate that Coptidis Rhizoma extract and its alkaloids can ameliorate the cell damage associated with ONOO− generation in renal tubular LLC-PK1 cells, and that the various alkaloids have distinctive mechanisms of action, such as ONOO− scavenging, protection from DNA damage and control of the cell cycle. Furthermore, the data suggest that among the Coptidis Rhizoma alkaloids, coptisine is the most effective for protection against SIN-1-induced cellular injury in terms of its potency and content.