A spermine alkaloid with diverse biological activities
Kukoamine A is a spermine alkaloid originally isolated from L. chinense that has diverse biological activities, including anticancer, neuroprotective, and anti-inflammatory properties. Kukoamine A (5-20 µg/ml) inhibits colony formation of U251 and WJ1 glioblastoma cells in a concentration-dependent manner. It halts the cell cycle at the G0/G1 phase and induces apoptosis when used at concentrations of 60 and 80 µg/ml. Kukoamine A (20 and 40 µM) induces autophagy and increases cell viability in an SH-SY5Y cell model of MPP-induced injury. It increases the number of dopamine neurons in the substantia nigra and striatum, decreases α-synuclein expression, and improves motor function in an MPTP mouse model of Parkinson's disease when administered at a dose of 20 mg/kg per day. Kukoamine A (10 and 20 mg/kg) decreases IL-1β, TNF-α, and COX-2 protein levels in the hippocampus and increases hippocampal neurogenesis in a rat model of radiation injury. It also selectively inhibits trypanothione reductase (Ki = 1.8 µM), an enzyme that protects certain parasites from oxidative stress, over human glutathione reductase (Ki = >10 mM).
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