Resveratrol is a polyphenol that plays a potentially important role in many disorders and has been studied in different diseases. The research on this chemical started through the “French paradox,” which describes improved cardiovascular outcomes despite a high-fat diet in French people. Since then, resveratrol has been broadly studied and shown to have antioxidant, anti-inflammatory, anti-proliferative, and anti-angiogenic effects, with those on oxidative stress possibly being most important and underlying some of the others, but many signaling pathways are among the molecular targets of resveratrol. In concert they may be beneficial in many disorders, particularly in diseases where oxidative stress plays an important role. The main focus of this review will be the pathways affected by resveratrol. Based on these mechanistic considerations, the involvement of resveratrol especially in cardiovascular diseases, cancer, neurodegenerative diseases, and possibly in longevity will be is addressed.

Controversy exists about the effect of zinc on growth and the GH-IGF system. Zinc supplementation has been shown to stimulate linear growth in zinc-deficient children. However the mechanism of this effect has not been well characterized. Furthermore, the effect of zinc supplementation on non-zinc-deficient short children is unknown. We investigated the effect of zinc supplementation on endogenous GH secretion, serum IGF-I and IGFBP-3 concentrations, IGF-I and IGFBP-3 generation in response to exogenous GH, bone formation markers, and linear growth of non-zinc-deficient children with idiopathic short stature. We analyzed prospectively serum zinc, IGF-I, IGFBP-3, alkaline phosphatase, osteocalcin, and GH response to clonidine test, and performed a somatomedin generation test before and 6 weeks after zinc supplementation in 22 (16 M, 6 F) prepubertal children with idiopathic short stature. Serum IGF-I increased from 67.4+/-70.6 to 98.2+/-77.3 ng/ml (p <0.001), IGFBP-3 from 2326+/-770 to 2758+/-826 ng/ml (p <0.001), alkaline phosphatase from 525+/-136 to 666+/-197 U/l (p <0.0001), and osteocalcin from 16.8+/-10.6 to 25.8+/-12.8 ng/ml (p <0.05) after zinc supplementation despite there being no difference in GH response to clonidine after zinc supplementation (peak GH 11.6+/-6.9 vs 13.4+/-7.8 ng/ml, GH area under the curve during clonidine test 689+/-395 vs 761+/-468, NS). Percent change in IGF-I and IGFBP-3 during the somatomedin generation test was not significantly affected by zinc supplementation (118% vs 136% and 57% vs 44%, respectively). There was no significant correlation between percentage increase in zinc levels and percentage increase in parameters tested. Height SDS or weight SDS did not improve significantly in 17 patients who continued on zinc supplementation for at least 6 months (6-12 months) (-2.59 vs -2.53 SDS and -1.80 vs -1.67 SDS, respectively). Zinc supplementation increased basal IGF-I, IGFBP-3, alkaline phosphatase and osteocalcin without changing GH response to clonidine. Zinc supplementation did not affect sensitivity to exogenous GH as tested by IGF-I and IGFBP-3 generation test. These results suggest a direct stimulatory effect of zinc on serum IGF-IGFBP-3, alkaline phosphatase and osteocalcin. Despite improvements in the above parameters, zinc supplementation to children with idiopathic short stature with normal serum zinc levels did not significantly change height or weight SDS during 6-12 months follow-up.

In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells.

Chronic myeloid leukemia is a major hematopoietic malignancy characterized by expansion of myeloid cells. In this study, we have investigated whether quercetin, curcumin and their combination induce apoptosis and inhibit growth of K562 cells. We have observed that quercetin and curcumin combination induced apoptosis accompanied by increased ROS and decreased GSH levels as well as loss of mitochondrial membrane potential. Our mRNA and protein expression results suggested that cytochrome c was released from mitochondria causing PARP and caspase-9 cleavages, the hallmarks of mitochondrial apoptotic pathway. We believe that triggering of apoptosis is mostly via mitochondrial pathway and ROS generation may induce impairment of mitochondrial membrane potential. The use of quercetin and curcumin combination potentiates individual apoptotic effects of the polyphenols and reduces their effective dose thereby preventing potential toxic effects on normal cells. Additional preclinical studies and clinical trials are certainly required to further validate their usefulness as potent anticancer agents.