Inhibition of melanin production by sesquiterpene lactones from Saussurea lappa and their analogues

Abstract

This research is aimed towards the discovery of a novel skin whitening agent from sesquiterpene lactones. We screened nine sesquiterpene lactones from Saussurea lappa root extracts, costunolide (1), α-, β-, γ-cyclocostunolides (2, 3, 4), santamarine (5), reynosin (6), arbuscirin A (7), dehydrocostus lactone (8), and 11β, 13-dehydrocostus lactone (9), for their melanin inhibitory activity in B16 melanoma cells. This study was focused on the inhibition of the extracellular melanin content. The screening results revealed that only α-cyclocostunolide (2) showed notable inhibition of the melanin production, particularly the extracellular melanin content, with an IC50 value of 5.75 μM. In addition, structure-activity relationship (SAR) of 12 sesquiterpene lactone analogues with reference to their melanin inhibitory activity was also investigated. However, none of the analogues were found to show any significant melanin inhibitory activity. To the best of our knowledge the above study is the first SAR investigation involving the melanin inhibitory activity of sesquiterpene lactones. It established that eudesmanolide-type lactone having a double bond between C3 and C4 showed the most efficient melanin inhibition. Additionally, the presence of a hydroxyl, ketone or ester moiety as the C1-substituent markedly decreased the melanin inhibitory activity. Thus, these findings suggest that α-cyclocostunolide (2) might be useful in the therapy of skin disorders.