Enhanced retinoid response by a combination of the vitamin A ester retinyl propionate with niacinamide and a flavonoid containingCeratonia siliquaextract in retinoid responsivein vitromodels

AbstractOBJECTIVESRetinoids have been used for decades as efficacious topical agents to treat photoaged skin. The purpose of our present research is to evaluate whether the activity of the Vitamin A ester retinyl propionate (RP) can be enhanced by niacinamide (Nam) and a flavonoid containingCeratonia siliqua(CS) fruit extract in retinoid responsivein vitromodels.METHODSRP was tested alone and in combination with Nam andCSin an RARα reporter cell line for promoter activation and compared totrans-retinoic acid (tRA) activation. These treatments were also tested in keratinocytes for gene expression profiling by qPCR using a panel of 40 retinoid responsive genes.RESULTStRA or RP elicited RARα reporter activation in a dose dependent manner. The combination of 0.5 μM or 2 μM RP with 10 mM Nam had a 56% and 95% signal increase compared to RP, respectively. The addition of 1%CSto 0.5 μM or 2 μM RP with 10 mM Nam elicited a further increase of 114% and 156%, respectively, over RP and Nam combinations. All retinoids elicited an increase in expression of 40 retinoid sensitive genes over control levels. Of the 40 genes 27 were enhanced by either 0.5 μM RP or 2 μM RP with 10 mM Nam and 1%CS. Nam orCShad very modest activity in both models.CONCLUSIONThe combination of RP with Nam andCSshowed a higher retinoid response than RP in two separate retinoid responsivein vitromodels. We hypothesize Nam andCSenhances RP activity by modulating metabolism to tRA via increasing NAD+pools and inhibiting reduction of retinal (RAL) back to retinol, respectively. The findings provide evidence that this combination may have enhanced efficacy for treating the appearance of photoaged skin.