Corynoxeine

Planta Med. 2015 Jan;81(1):46-55.

Isolation and identification of twelve metabolites of isocorynoxeine in rat urine and their neuroprotective activities in HT22 cell assay.[Pubmed: 25519834]

IsoCorynoxeine, one of the major alkaloids from Uncaria Hook, shows the effects of lowering blood pressure, vasodilatation, and protection against ischemia-induced neuronal damage. In this paper, the metabolism of isoCorynoxeine was investigated in rats. Twelve metabolites and the parent drug were isolated by using solvent extraction and repeated chromatographic methods, and determined by spectroscopic methods including UV, MS, NMR, and CD experiments.
METHODS AND RESULTS:
Seven new compounds were identified as 11-hydroxyisoCorynoxeine, 5-oxoisocorynoxeinic acid-22-O-β-D-glucuronide, 10-hydroxyisoCorynoxeine, 17-O-demethyl-16,17-dihydro-5-oxoisoCorynoxeine, 5-oxoisocorynoxeinic acid, 21-hydroxy-5-oxoisoCorynoxeine, and oxireno[18, 19]-5-oxoisoCorynoxeine, together with six known compounds identified as isoCorynoxeine, 18,19-dehydrocorynoxinic acid, 18,19-dehydrocorynoxinic acid B, Corynoxeine, isoCorynoxeine-N-oxide, and Corynoxeine-N-oxide. Possible metabolic pathways of isoCorynoxeine are proposed. Furthermore, the activity assay for the parent drug and some of its metabolites showed that isoCorynoxeine exhibited a significant neuroprotective effect against glutamate-induced HT22 cell death at the maximum concentration. However, little or weak neuroprotective activities were observed for M-3, M-6, M-7, and M-10.
CONCLUSIONS:
Our present study is important to further understand their metabolic fate and disposition in humans.

Biol Pharm Bull. 2008 Nov;31(11):2073-8.

Corynoxeine isolated from the hook of Uncaria rhynchophylla inhibits rat aortic vascular smooth muscle cell proliferation through the blocking of extracellular signal regulated kinase 1/2 phosphorylation.[Pubmed: 18981576]

The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. Uncaria rhynchophylla is traditional Chinese herb that has been applied to the treatment of convulsive disorders, such as epilepsy, in China.
METHODS AND RESULTS:
In the present study, we examined whether Corynoxeine exerts inhibitory effects on platelet-derived growth factor (PDGF)-BB-induced rat aortic VSMC proliferation and the possible mechanism of such effects. Pre-treatment of VSMCs with Corynoxeine (5-50 microM) for 24 h resulted in significant decreases in cell number without any cytotoxicity; the inhibition percentages were 25.0+/-12.5, 63.0+/-27.5 and 88.0+/-12.5% at 5, 20 and 50 microM, respectively. Also, Corynoxeine significantly inhibited the 50 ng/ml PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without any cytotoxicity; the inhibitions were 32.8+/-11.0, 51.8+/-8.0 and 76.9+/-7.4% at concentrations of 5, 20 and 50 microM, respectively. Pre-incubation of VSMCs with Corynoxeine significantly inhibited PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, whereas Corynoxeine had no effects on mitogen-activated protein kinase (MAPK/ERK)-activating kinase 1 and 2 (MEK1/2), Akt, or phospholipase C (PLC)gamma1 activation or on PDGF receptor beta (PDGF-Rbeta) phosphorylation.
CONCLUSIONS:
These results suggest that Corynoxeine is a potent ERK1/2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty.