Polyphenols and neuroprotection: Therapeutic implications for cognitive decline.

Dietary polyphenols have been the focus of major interest for their potential benefits on human health. Several preclinical studies have been conducted to provide a rationale for their potential use as therapeutic agents in preventing or ameliorating cognitive decline. However, results from human studies are scarce and poorly documented. The aim of this review was to discuss the potential mechanisms involved in age-related cognitive decline or early stage cognitive impairment and current evidence from clinical human studies conducted on polyphenols and the aforementioned outcomes. The evidence published so far is encouraging but contrasting findings are to be taken into account. Most studies on anthocyanins showed a consistent positive effect on various cognitive aspects related to aging or early stages of cognitive impairment. Studies on cocoa flavanols, resveratrol, and isoflavones provided substantial contrasting results and further research is needed to clarify the therapeutic potential of these compounds. Results from other studies on quercetin, green tea flavanols, hydroxycinnamic acids (such as chlorogenic acid), curcumin, and olive oil tyrosol and derivatives are rather promising but still too few to provide any real conclusions. Future translational studies are needed to address issues related to dosage, optimal formulations to improve bioavailability, as well as better control for the overall diet, and correct target population.

Fortified extract of red berry, Ginkgo biloba, and white willow bark in experimental early diabetic retinopathy.

Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries, Ginkgo biloba and white willow bark containing carnosine and α-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control) rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-α and VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS). Increased TNF-α and VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats.

Homology modeling of dopamine D2 and D3 receptors: molecular dynamics refinement and docking evaluation.

Dopamine (DA) receptors, a class of G-protein coupled receptors (GPCRs), have been targeted for drug development for the treatment of neurological, psychiatric and ocular disorders. The lack of structural information about GPCRs and their ligand complexes has prompted the development of homology models of these proteins aimed at structure-based drug design. Crystal structure of human dopamine D(3) (hD(3)) receptor has been recently solved. Based on the hD(3) receptor crystal structure we generated dopamine D(2) and D(3) receptor models and refined them with molecular dynamics (MD) protocol. Refined structures, obtained from the MD simulations in membrane environment, were subsequently used in molecular docking studies in order to investigate potential sites of interaction. The structure of hD(3) and hD(2L) receptors was differentiated by means of MD simulations and D(3) selective ligands were discriminated, in terms of binding energy, by docking calculation. Robust correlation of computed and experimental K(i) was obtained for hD(3) and hD(2L) receptor ligands. In conclusion, the present computational approach seems suitable to build and refine structure models of homologous dopamine receptors that may be of value for structure-based drug discovery of selective dopaminergic ligands.

Oral Echinacea purpurea extract in low-grade, steroid-dependent, autoimmune idiopathic uveitis: a pilot study.

AIM: The aim of to test efficacy and safety of Echinacea purpurea (echinacea) extract in the control of low-grade uveitis. METHODS: Fifty-one (51) patients with low-grade, steroid dependent, autoimmune uveitis were recruited; posterior uveitis was excluded. The start therapy was represented by topical desamethazone for anterior uveitis and oral prednisone, rapidly tapered, for anterior uveitis with inflammatory scores equal to +2 and in all cases of intermediate uveitis. Best-corrected visual acuity (BCVA) decrease or improvement was defined as a reduction or increase of 2 or more letters seen from the initial BCVA; ETDRS chart was used. Thirty-two (32) patients (21 with anterior uveitis and 11 with intermediate uveitis) received Echinacea (150 mg twice/day) as add-on therapy, whereas 20 patients (10 with anterior uveitis and 9 with intermediate uveitis) were treated with the conventional steroid therapy alone. RESULTS: Thirty-one (31) patients showed anterior uveitis and 20 intermediate uveitis. The follow-up duration was 9 months. At the last follow-up, 19/21 patients with anterior uveitis and 9/11 with intermediate uveitis treated with echinacea presented uveitis settled, with a steroid-off time of 209 and 146 days, respectively. BCVA was stable or improved in 19/21 of anterior uveitis and 9/11 of intermediate uveitis. No adverse reactions supposed to be resulting from commercial-grade echinacea were recorded. Patients who did not receive echinacea required a longer treatment period with steroids with a steroid-off time of 121 and 87 days. CONCLUSIONS: Systemic echinacea appears safe and effective in the control of low-grade autoimmune idiopathic uveitis.