In light of the increase in life expectancy, the risk of related neurodegenerative diseases and the lack of pharmacological solutions able to counteract this process, research in recent years has begun to look with great interest to the world of so-called natural products. Among the most studied, certainly curcumin, by virtue of its anti-inflammatory and antioxidant properties. A review recently published in Nutrients has taken stock of the pre-clinical and clinical data available today with respect to its possible use for neuroprotective purposes.
Oxidative stress and neuroinflammation are critical factors in the neurodegenerative process. Among the most interesting aspects of curcumin there is certainly its ability to act as an antioxidant, as an anti-inflammatory and, thanks to its unique molecular structure, also to be able to directly affect the beta-amyloid plaques in specific pathological conditions such as Alzheimer’s disease. This last characteristic, together with the typical fluorescence that distinguishes it, makes curcumin interesting also from the diagnostic point of view and for monitoring the progression of those degenerative diseases similar to Alzheimer. As for the anti-inflammatory properties, curcumin is able to block the transcription factor NF-kB, resulting in a reduction in the production of pro-inflammatory cytokines. As an antioxidant, however, is able to act both as a “sweeper” of free radicals, both through the transcription factor Nrf2 whose enhancement leads to increased production of antioxidant enzymes. In addition, over the long term, curcumin stimulates and strengthens the body’s defenses making it more efficient and ready to face stressful conditions. It is precisely this second aspect, together with the characteristics previously mentioned, to make the use of curcumin extremely promising in the context of strategies aimed at prevention, rather than cure, of neurodegenerative diseases.
The results of preclinical studies are generally in favor of the use of curcumin in the clinical setting and are of fundamental importance to identify strengths and weaknesses to be submitted to the attention of pharmacological research. Curcumin, even in animal models very different from each other, has been shown to be very effective in reducing oxidative stress by consistently reducing systemic inflammation but especially neuroinflammation. As for clinical studies, to date only a few have focused on the effect of curcumin on cognitive decline in humans and the results are not always consistent with each other. This is due in part to a problem of bioavailability of the substance, aspect on which the pharmaceutical industry is working hard, but also to the heterogeneity of dosing protocols and duration of administration, the age of the cohorts under study, as well as the response variables observed. Put together, all these aspects often make comparison between studies complex and suggest that there is a real need to implement clinical trials with solid experimental designs and protocols as standardized as possible.
We know that in women the arrival of menopause is an important risk factor for general health and often coincides with the onset of cognitive decline that can give rise to dementia also associated with neurodegeneration. Since curcumin supplementation should be intended as a preventive strategy, we can imagine that its use in women, in the typical age when the first symptoms of menopause begin to be observed, or even before, could be particularly effective in counteracting or delaying the onset of cognitive decline.
Curcumin is characterized by low water solubility, high instability in most body fluids, and poor intestinal absorption. Thus, in general, the biggest problem with respect to its supplementation is its poor bioavailability. In other words, the amount of substance that reaches the circulation without being modified is minimal. Just this criticality, together with the indications coming from preclinical and clinical studies on the high potential of curcumin in counteracting cognitive decline, is pushing the pharmaceutical industry towards the development of formulations able to increase its bioavailability and therapeutic/preventive efficacy. Despite its low bioavailability, it should be noted that the intestinal flora is able to produce active metabolites with high neuroprotective potential, an aspect that makes even more interesting the use of curcumin in the context of neurodegenerative diseases.
The pharmaceutical industry is clearly oriented towards oral formulations, which are also those most accepted by the general population, characterized by high stability and resistance in the passage through the gastrointestinal system and aimed at reducing its metabolization and increasing its permanence in the bloodstream. From this point of view, the use of new technologies is showing particular promise. Clinical studies aimed at testing the effectiveness of transporters such as, for example, phytosomes, able to increase both intestinal absorption and permeability within the cells of curcumin, are giving very promising results.
The basic research and the few clinical studies carried out so far have provided very convincing indications on the effectiveness of curcumin in counteracting cognitive decline. Among the critical issues that must be addressed and resolved there is certainly the aspect related to the bioavailability of this substance. It is also of fundamental importance to identify specific populations at risk such as, for example, pre-menopausal women and take into account the effects of nutritional status, diet and lifestyle in assessing the effectiveness of curcumin. Another critical issue is certainly the future ability to identify reliable and possibly minimally invasive biomarkers of efficacy. Moreover, because women are characterized by a greater vulnerability to Alzheimer’s-like neurodegenerative diseases, such studies should also take into account gender-specific effects.
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