Abstract:

Novel biomarker-supported pharmacotherapeutic exploitation of substances of ayurvedic origin. The example of curcumin.

Background. Curcuma longa has been utilized for various medical purposes for several
hundred years in traditional Indian medicine. Nevertheless, the medical evidence to support
its use is almost lacking, similar to underlying pharmacological mechanisms responsible for
curative effects in either experimental animals or clinical patients.
Aim. Our preceding experimental studies with rats revealed that an improvement in spatial
memory performance occurred both in aged rats with Alzheimer disease model characteristics
and scopolaminne-induced memory impairment model. We carried out a series of
experiments using with rats to estimate the putative cognitive function improving effects of
curcumin, the active ingredient of curcuma longa at the aforementioned paradigm. We also
approached mechanisms explaining curcumin effects.
Methods and Results. A significant improvement in spatial memory was observed in aged
male, otherwise healthy Winstar rats weighing 500-550 g and in those with insulin resistance
determined by hyperinsulinaemic euglycaemic glucose clamping. However, insulin resistance
per se was found to deteriorate cognitive performance. The memory improving effect was
dose dependent and strongly significant at a curcumin dose range of 0.3-100 mg/kg body
weight given orally twice a day over a period of 7 days. A dose-dependent insulin sensitizing
effect was also seen in insulin resistant animals. The memory improving effect was correlated
with a D-amino acid oxydase (DAAO) inhibitory effect of curcumin, whereas the insulin
sensitizing effect was found to interact with an endogenous insulin sensitizing mechanism
known as meal-induced insulin sensitization. A pilot clinical study with 12 aged volunteers
confirmed the memory improving effect of a preparation containing curcuma longa rhizoma
extract with a pure curcumin equivalent of approx. 100 mg twice a day.
Conclusion. Curcumin induces an improvement of cognitive performance in both
experimental animals and aged human voluteers. The effect is underpinned by DAAO
inhibition. This effect is supported by insulin sensitization produced by curcumin, the
mechanism of which seems to be independent of DAAO inhibition.