795 Acetyl-arctigenin (Ac-ATG), a novel and safe skin lightening molecule

Abstract

There is high demand to identify novel skin lightening actives that are effective and safe. Previously, it has been shown that arctigenin (ATG) found in A. lappa, inhibits melanogenesis. To explore this chemotype further and identify more potent skin lightening actives, several ATG derivatives were synthesized including acetyl-arctigenin (Ac-ATG). Utilizing murine melanoma cells, ATG and Ac-ATG both reduce melanin content, with Ac-ATG demonstrating increased potency. However, when measuring tyrosinase inhibition capacity, both ATG and Ac-ATG showed modest inhibitory activity (20-25%), while kojic acid (KA) reached almost 100% inhibition. Endothelin-1 (ET-1) is a key mediator for melanocytes in UVB induce pigmentation and melanosome transfer. Our results show both ATG and Ac-ATG inhibit ET-1 in human epidermal keratinocytes. We thus sought to evaluate the anti-melanogenesis activity of Ac-ATG and ATG when applied topically (MelanoDerm™). Results show that after 2 weeks, both 0.1% ATG and 0.1% Ac-ATG significantly reduce melanin production by 56% and 72% respectively. Moreover, 1% Ac-ATG results in an 84% inhibition of melanin, which is significantly greater than 2% KA (62% inhibition). Interestingly, when 0.1% Ac-ATG was combined with 2% KA, we observed an additive effect resulting in 96% reduction in melanin. Moreover, this effect is not observed when 0.1% ATG and 2% KA are combined (62% inhibition). Additional studies need to be performed to elucidate Ac-ATG’s mechanism of action. Lastly, safety assessment for Ac-ATG including, in vitro sensitization, skin and eye irritation, Ames test, phototoxicity and HRIPT have been performed and in all instances, Ac-ATG was found to be safe. Thus, Ac-ATG is a novel, safe depigmentation compound and our results suggest that it can be utilized as both a stand-alone skin lightning ingredient and/or in combination with other depigmentation compounds that function through different mechanisms.