Coptis chinensis rhizomes (CR) are one important ingredient of traditional Chinese herbal formulas such as San-Huang-Xie-Xin-\nTang which is used for treatment of cardiovascular and neurodegenerative diseases. Recent studies suggest that the extract of CR\nmight be a potential therapeutic agent for amelioration of neurological disorders associated with oxidative stress. In the present\nstudy we aimed at revealing the main active compound(s) of the CR extract and at investigating the mechanism of action. Four\nmain alkaloids of the CR extract (berberine, coptisine, jatrorrhizine, and palmatine) were selected for this study. Results showed\nthat out of those alkaloids only pretreatment with coptisine significantly attenuated tert-butylhydroperoxide induced reduction\nof cell viability, increased rate of apoptosis, and declined mitochondrial membrane potential. Elisa assay and quantitative realtime\nPCR analyses revealed that thioredoxin-interacting protein (TXNIP) gene expression was downregulated by coptisine, which\ncould explain the neuroprotective effect, hypothetically, by strengthening the thioredoxin defense system against oxidative stress\nand attenuation of apoptosis signal-regulating kinase (Ask1) mediated apoptotic signaling. A comparison between coptisine and\nCR extract identified coptisine as themain single component responsible for the neuroprotective effect. Based on the results the CR\nextract and coptisine are promising candidate agents for prevention or improvement of diabetic neuropathy and neurodegenerative\ndisorders.
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