Dietary Curcumin Ameliorates Aging-Related Cerebrovascular Dysfunction through the AMPK/Uncoupling Protein 2 Pathway

Abstract

Background/Aims: Age-related cerebrovascular dysfunction contributes to stroke, cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases. One pathogenic mechanism underlying this effect is increased oxidative stress. Up-regulation of mitochondrial uncoupling protein 2 (UCP2) plays a crucial role in regulating reactive oxygen species (ROS) production. Dietary patterns are widely recognized as contributors to cardiovascular and cerebrovascular disease. In this study, we tested the hypothesis that dietary curcumin, which has an antioxidant effect, can improve aging-related cerebrovascular dysfunction via UCP2 up-regulation. Methods: The 24-month-old male rodents used in this study, including male Sprague Dawley (SD) rats and UCP2 knockout (UCP2-/-) and matched wild type mice, were given dietary curcumin (0.2%). The young control rodents were 6-month-old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The AMPK/UCP2 pathway and p-eNOS in cerebrovascular and endothelial cells were observed by immunoblotting. Results: Dietary curcumin administration for one month remarkably restored the impaired cerebrovascular endothelium-dependent vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up-regulated UCP2 and reduced ROS production. These effects of curcumin were abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin significantly reduced ROS production and improved cerebrovascular endothelium-dependent relaxation in aging wild type mice but not in aging UCP2-/- mice. Conclusions: Curcumin improves aging-related cerebrovascular dysfunction via the AMPK/UCP2 pathway.

Protective effects of Brassica oleracea sprouts extract toward renal damage in high-salt-fed SHRSP

“…The latter, a naturally occurring polyphenol from the plant Curcuma longa, AMPK/PPARa/UCP2 and renal damage in hypertension has been shown to significantly decrease ROS production and improve cerebrovascular endotheliumdependent relaxation in aging rats [47]. Similarly to our results, curcumin administration increased cerebrovascular AMPK phosphorylation and UCP2 levels both in vitro and in vivo.…”

“…Interestingly, the properties of B. oleracea outlined in our experimental context appear to be quite similar to those described for curcumin [47]. The latter, a naturally occurring polyphenol from the plant Curcuma longa, AMPK/PPARa/UCP2 and renal damage in hypertension has been shown to significantly decrease ROS production and improve cerebrovascular endotheliumdependent relaxation in aging rats [47].…”

Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells

“…Curcumin promoted eNOS activity in cultured endothelial cells or in vivo rats that ameliorated aging-related cerebrovascular dysfunction. 40 Cadmium-induced vascular dysfunction and hypertension in mice are effectively attenuated by curcumin treatment in which increased eNOS expression is involved. 27 Boonla et al 41 have demonstrated that curcumin improves vascular remodeling and endothelial dysfunction in hypertensive rats associated with an upregulation of eNOS.…”

Curcumin inhibits growth of prostate carcinoma via miR-208-mediated CDKN1A activation

“…Curcumin, which is termed as 1,7-bis(4-hydroxy-3-m e t h o x y p h e n y l ) -1 , 6 -h e p a t a d i e n e -3 , 5 -d i o n e , o r diferulolylmethane, is a major constituent of the yellow spice turmeric that is extracted from the rhizome of the plant Curcuma longa [9][10][11][12][13]. Curcumin has been shown of anticancer effects in a number of cancers, including PC [9,[14][15][16][17][18].…”