Nitric oxide (NO), a short-lived free radical generated endogenously, exerts influence on a number of functions including vasodilation, neurotransmission, synaptic plasticity and memory in the central nervous system. 1,2) Besides mediating normal function, NO has been implicated in pathophysiologic states. Overproduction of NO can mediate toxic effects, e.g. DNA fragmentation, cell damage and neuronal cell death.3) NO also shows neurotoxicity and acts as a pathological mediator in pathophysiological processes such as cerebral ischemia, epilepsy, Alzheimer's disease, Parkinson's disease and certain neurodegenerative disease.
4)Curcumin (diferuloylmethane) is a major active component of the food flavour tumeric. It is extracted from the powdered dry rhizome of Curcuma longa LINN (Zingiberaceae), a perennial herb widely cultivated in tropical regions of Asia. It has been used for centuries in indigenous medicine for the treatment of a variety of inflammatory, and infectious diseases, cancer and other diseases. 5,6) Several studies have shown that a trigger mechanism that allows for the treatment of many diseases is due to its antioxidant properties. Curcumin is a powerful scavenger of many free radicals such as superoxide anion, 7) hydroxyl radical 8) and nitric oxide.
9)In a previous study, Vajragupta et al. synthesized the manganese complexes of the curcumin and diacetylcurcumin as superoxide dismutase mimics. The structures of curcumin and its derivatives are shown in Fig. 1. Superoxide dismutase (SOD) enzyme is the metalloenzyme that catalyzes the dismutation of superoxide anion to hydrogen peroxide and dioxygen. Curcumin manganese complex (CpCpx) and diacetylcurcumin manganese complex (AcylCpCpx) are low molecular weight synthetic compounds that showed much greater SOD activity and an inhibitory effect on lipid peroxidation.10) AcylCpCpx also gave the highest inhibitory activity to H 2 O 2 -induced cell damage (oxidative stress) in NG108-15 cells, which were more potent than curcumin and acetylcurcumin. In addition, the manganese complexes also potentiated neuroprotective effects against learning and memory impairment in transient cerebral ischemic mice.
11)The aim of this study is to investigate the effect of CpCpx and AcylCpCpx on NO radical scavenging in vitro using a * To whom correspondence should be addressed. e-mail: hwatanab@ms.toyama-mpu. Curcumin manganese complex (CpCpx) and diacetylcurcumin manganese complex (AcylCpCpx) were determined as to their effect on the nitric oxide (NO) radical scavenging in vitro method using a sodium nitroprusside generating NO system compared with their parent compound and astaxanthin, an extreme antioxidant. All compounds effectively reduced the generation of NO radicals in a dose dependent manner. They exhibited strong NO radical scavenging activity with low IC 50 values. The IC 50 values of curcumin, diacetylcurcumin, CpCpx and AcylCpCpx obtained are 20.39؎4.10 m mM, 28.76؎1.48 m mM, 9.79؎1.50 m mM and 8.09؎0.99 m mM, respectively. CpCpx and AcylCpCpx show greater NO...