Protective role of Coptidis Rhizoma alkaloids against peroxynitrite-induced damage to renal tubular epithelial cells.
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-PK(1) cell under peroxynitrite (ONOO(-)) generation model. Treatment with 3-morpholinosydnonimine (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 G(0)/G(1)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 10 microg mL(-1). These findings demonstrate that Coptidis Rhizoma extract and its alkaloids can ameliorate the cell damage associated with ONOO(-) generation in renal tubular LLCPK(1) 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.
Yokozawa
Takako
T
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. yokozawa@ms.toyama-mpu.ac.jp
Satoh
Akiko
A
Cho
Eun Ju
EJ
Kashiwada
Yoshiki
Y
Ikeshiro
Yasumasa
Y
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D000089042:Coptis chinensis; D053938:DNA Fragmentation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018374:LLC-PK1 Cells; D015394:Molecular Structure; D008981:Molsidomine / Q000009:adverse effects / Q000031:analogs & derivatives*; D030421:Peroxynitrous Acid / Q000096:biosynthesis*; D013552:Swine; D019459:Urothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D030421:Peroxynitrous Acid; C002385:linsidomine; C107393:Coptidis rhizoma extract; D008981:Molsidomine