Coptidis Rhizoma: protective effects against peroxynitrite-induced oxidative damage and elucidation of its active...

We have investigated the protective effects of Coptidis Rhizoma against peroxynitrite (ONOO(-))-induced oxidative damage and have elucidated the active components of this preparation. In an in-vitro system, Coptidis Rhizoma extract scavenged ONOO(-) and its precursors, nitric oxide (NO) and superoxide anion (O(2)(-)). This scavenging activity was more marked for ONOO(-) than its precursors. In addition, against 3-morpholinosydnonimine-induced cellular damage, this extract significantly reduced cellular ONOO(-) formation and increased cell viability. In an in-vivo lipopolysaccharide plus ischaemia-reperfusion system that generated ONOO(-), the administration of Coptidis Rhizoma extract at 50 and 100 mg kg(-1)/day for 30 days exerted greater inhibition of ONOO(-) than NO and O(2)(-). This suggested that it acted as a direct scavenger of ONOO(-) rather than as a scavenger of its precursors. Moreover, the suppression of the activities of the antioxidative enzymes superoxide dismutase, catalase and glutathione peroxidase was significantly attenuated by the administration of Coptidis Rhizoma extract. Furthermore, the extract ameliorated renal dysfunction judged by decreasing serum urea nitrogen and creatinine levels. To elucidate the active components of Coptidis Rhizoma extract, we evaluated and compared the effects of the phenol plus alkaloid and alkaloid fractions on ONOO-induced damage. We found that the alkaloid fraction consisting of berberine, palmatine and coptisine was the most effective at protecting against ONOO(-). We confirmed that berberine (10 and 20 mg kg(-1)/day for 10 days), the main and most active alkaloid in Coptidis Rhizoma extract, was also protective, exerting NO-, O(2)(-)- and ONOO(-)-scavenging activities. This study suggested that Coptidis Rhizoma could protect against ONOO(-)-induced oxidative damage and that this effect was mainly attributable to the constituent alkaloids, especially berberine. This study is the first to demonstrate an antioxidative effect of alkaloids, including berberine, against ONOO(-)-induced damage.