Regarded as a ‘Rasayana’ herb in Ayurveda to counteract ageing processes, Curcuma longa L. (Zingiberaceae) has also been used for culinary purposes and in the textile industry. Much research has focused on curcumin, a curcuminoid from C. longa rhizomes, and it has been shown to modulate a variety of molecular targets. In particular, studies have shown that some curcuminoids are associated with antioxidant and anti-inflammatory activities, but in general, studies with particular attention to cognitive disorders and any clinical relevance are lacking. In addition, further evaluation of potentially active compounds from Curcuma longa, other than the curcuminoids, may contribute to the understanding of the traditional uses of this herb. The antioxidant activity of curcumin is well documented, and it is suggested to be the underlying mechanism to explain a number of beneficial effects on cognition. Curcumin was shown to be neuroprotective in vitro and protected against ethanol-induced brain injury in vivo following oral administration, an effect that was related to a reduction in lipid peroxide levels and enhancement of glutathione in rat brain. A neuroprotective action of curcumin was also observed in an animal model of Parkinson’s disease, an effect also attributed to its antioxidant properties. It also dose-dependently improved motor and cognitive impairment and significantly attenuated the associated oxidative stress in the brain when orally administered to rodents. Some compounds from Curcuma longa, including curcumin, demethoxycurcumin, bisdemethoxycurcumin and calebin A (and some synthetic analogues), were shown to protect PC 12 cells from β-amyloid insult in vitro; this activity was also suggested to be due to an antioxidant effect. It is proposed that the hydrophobic bridge of the conjugated network in the curcumin structure enables penetration into the blood-brain barrier, and the more hydrophilic phenolic polar groups are important for its binding to β-amyloid.
Curcumin is also reported to be anti-inflammatory and has been suggested to modulate eicosanoid biosynthesis and COX-1, COX-2 and lipoxygenase (lipoxygenase) activities. It also inhibits nuclear transcription factor kB (NF-kB) activation, although the clinical significance of the latter action in cognitive disorders is unclear. Attempts to improve selectivity for the cyclo-oxygenase enzymes and efficacy by developing compounds based on the structures of the curcuminoids could be a route to new anti-inflammatory drugs. Some curcuminoid pyrazole and isoxazole analogues have been synthesised and are reported to inhibit cyclo-oxygenase and to be anti-inflammatory in vivo, and it was shown that replacement of the beta-diketo in the curcumin structure with a pyrazole ring enhanced the COX-2/COX-1 selectivity.