Photoprotection by 1(alpha),25-Dihydroxyvitamin D3 and vitamin D-like compound in human skin

Abstract

Ultraviolet radiation causes deleterious effects in skin and also produces of vitamin D which is known to provide photoprotection. Although the mechanism is still unclear, there is evidence suggesting that non genomic pathways are responsible for the photoprotective effects. Several VDR alternative pocket ligands with capacity for triggering the nongenomic response without ability to trigger the genomic pathway have shown comparable degree of photoprotection in earlier studies by the Mason group. This current study examined the photoprotective effect of tetrahydrocurcumin (THC), a major in vivo metabolite of curcumin (CUR) which is known to be a ligand for the VDR alternative pocket, in parallel with an active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), in human ex vivo skin, followed by a randomized clinical trial in human subjects. Both the ex vivo study and clinical trial showed that 1,25(OH)2D3 and THC produced similar reductions in UV-induced DNA lesions, supporting the involvement of the nongenomic pathway. The clinical trial also showed for the first time, several types of DNA repair proteins including DNA damage binding protein 2 (DDB2), xeroderma pigmentosum complementation group C (XPC), and oxoguanine glycosylase 1 (OGG1) were upregulated with 1,25(OH)2D3 or THC, indicating that improved DNA repair may be a key mechanism for photoprotection.