| J Alzheimers Dis. 2015;43(1):291-302. |
| The IDO inhibitor coptisine ameliorates cognitive impairment in a mouse model of Alzheimer's disease.[Pubmed: 25079795]|
|Indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme in the kynurenine pathway (KP) of tryptophan catabolism, was recently established as one of the potential players involved in the pathogenesis of Alzheimer's disease (AD). Coptisine is a main pharmacological active constituent of the traditional Chinese medicinal prescription Oren-gedoku-to (OGT) which has therapeutic potential for the treatment of AD. Our recent studies have demonstrated that OGT significantly inhibited recombinant human IDO activity, which shed light on the possible mechanism of OGT's action on AD. |
METHODS AND RESULTS:
Here, we characterized the effects of Coptisine in an AD mouse model on the basis of its IDO inhibitory ability. Coptisine was found to be an efficient uncompetitive IDO inhibitor with a Ki value of 5.8 μM and an IC50 value of 6.3 μM. In AβPP/PS1 transgenic mice, oral administration of Coptisine inhibited IDO in the blood and decreased the activation of microglia and astrocytes, consequently prevented neuron loss, reduced amyloid plaque formation, and ameliorated impaired cognition. Neuronal pheochromocytoma (PC12) cells induced with amyloid-β peptide 1-42 and interferon-γ showed reduction of cell viability and enhancement of IDO activity, while Coptisine treatment increased cell viability based on its reversal effect on the enhanced activity of IDO.
In conclusion, our present findings provide further evidence supporting the critical links between IDO, KP, and AD, and demonstrate Coptisine, a novel IDO inhibitor, as a potential new class of drugs for AD treatment.
|Clin Exp Pharmacol Physiol. 2004 Jan-Feb;31(1-2):65-9. |
|Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth.[Pubmed: 14756686]|
|1. The present study was conducted to evaluate the cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents on hepatoma and leukaemia cells in vitro. |
METHODS AND RESULTS:
2. Four human liver cancer cell lines, namely HepG2, Hep3B, SK-Hep1 and PLC/PRF/5, and four leukaemia cell lines, namely K562, U937, P3H1 and Raji, were used in the present study. 3. Of the two crude drugs, C. chinensis exhibited the strongest activity against SK-Hep1 (IC50 = 7 microg/mL) and Raji (IC50 = 4 microg/mL) cell lines. The IC50 values for C. chinensis on HepG2, Hep3B and PLC/PRF/5 cell lines were 20, 55 and 35 microg/mL, respectively. The IC50 values for C. chinensis on K562, U937 and P3H1 cell lines were 29, 29 and 31 microg/mL, respectively. 4. With the exception of HepG2 and Hep3B, the E. sagittatum extract inhibited the proliferation of all cell lines (SK-Hep1, PLC/PRF/5, K562, U937, P3H1 and Raji), with IC50 values of 15, 57, 74, 221, 40 and 80 microg/mL, respectively. 5. Interestingly, the two major compounds of C. chinensis, berberine and Coptisine, showed a strong inhibition on the proliferation of both hepatoma and leukaemia cell lines, with IC50 values varying from 1.4 to 15.2 microg/mL and from 0.6 to 14.1 microg/mL, respectively. However, icariin (the major compound of E. sagittatum) showed no inhibition of either the hepatoma or leukaemia cell lines.
6. The results of the present study suggest that the C. chinensis extract and its major constituents berberine and Coptisine possess active antihepatoma and antileukaemia activities.
|Atherosclerosis. 2013 Dec;231(2):384-91. |
|Coptisine protects rat heart against myocardial ischemia/reperfusion injury by suppressing myocardial apoptosis and inflammation.[Pubmed: 24267256]|
|Protecting the heart from myocardial ischemia and reperfusion (I/R) damage is the focus of intense research. Coptisine is an isoquinoline alkaloid isolated from Coptidis Rhizoma. The present study investigated the potential effect of Coptisine on myocardial I/R damage in rats and the underlying mechanisms.
METHODS AND RESULTS:
Electrocardiogram examination showed that the administration of Coptisine 10 min before ischemia significantly decreased I/R-induced arrhythmia after 30 min ischemia followed by 3 h reperfusion. The release of cardiac markers was also limited. Echocardiography was performed before ischemia and 24 h post-I/R, separately. The M-mode records showed that the reductions of ejection fraction (EF) and fractional shortening (FS) were attenuated in Coptisine-treated rats compared with the I/R rats. Similar results were obtained with Evans Blue/triphenyl tetrazolium chloride (TTC) staining, in which Coptisine notably reduced infarct size. Moreover, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated Coptisine suppressed myocardial apoptosis, which may be related to the upregulation of Bcl-2 protein and inhibition of caspase-3 activation. Coptisine treatment also attenuated the proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in heart tissue. Additionally, Western blot and immunohistochemical analysis showed that Coptisine markedly reduced Rho, Rho-kinase 1 (ROCK1), and ROCK2 expression and attenuated the phosphorylation of myosin phosphatase targeting subunit-1, a downstream target of ROCK.
Coptisine exerts pronounced cardioprotection in rats subjected to myocardial I/R likely through suppressing myocardial apoptosis and inflammation by inhibiting the Rho/ROCK pathway.