J. Cosmet. Sci., 65, 103–113 (March/April 2014) 103 Fucus extract: cosmetic treatment for under-eye dark circles MANASI CHAVAN, YUHUA SUN, JILL LITCHAUER, and ALAIN DENIS, BASF Beauty Creations, Stony Brook, NY 11790. Accepted for publication March 10, 2014. Synopsis Background: Dark circles around the eyes are a complex issue with two main possible causes, the accumula- tion of melanin in the skin around the eyes and the accumulation of heme resulting from blood leakage. The free heme produced in this manner is highly cytotoxic, proinfl ammatory and pro-oxidative. Aims: To evalu- ate the effect of Fucus extract on heme oxygenase-1 (HO-1) stimulation activity, and to study its in vitro anti-infl ammatory, antioxidative, and collagen stimulation activity. Methods: The HO-1 stimulation activity was fi rst evaluated at gene level by reverse transcriptase- polymerase chain reaction targeting specifi c HO-1 gene, and then followed by Western blot in protein level. The in vitro anti-infl ammatory effect was measured by quantifi cation of interleukin-8 (IL-8) level. The in vitro antioxidative activity was measured. Collagen stimulation activity was quantitatively measured by the amount of deposited collagen I in the extracellular matrix. Results: Fucus extract was identifi ed to have HO-1 stimulation activity at both gene and protein level. By stimulating this enzyme, it promotes the degradation of toxic heme to its protective catabolites (CO, Ferritin, and bilirubin) and reduces the source of dark circles. In addition, Fucus extract showed good anti-infl ammatory effi cacy. The strong antioxidation property of Fucus extract can reduce eye bags and wrin- kles while its collagen boosting activity will potentially reduce fi ne lines and wrinkles. Conclusion: Fucus extract is a novel product that brings a quadruple approach to the treatment of under-eye dark circles. INTRODUCTION DARK CIRCLES AND CAUSES Dark circles around the eyes are a complex issue with many possible causes. Based on recent research, two factors are clearly defi ned as major causes. First is the accumulation of melanin in the skin around the eyes. Melanin is produced by melanocytes and is trans- ferred to keratinocytes to protect the nucleus from ultraviolet radiation. Selective accu- mulation of melanin around eye area will cause a dark circle. Second is the accumulation of heme resulted from blood leakage (1). The dilated blood vessels in the dermis lead to blood leakage into the surrounding areas including epidermis. Degradation of leaked red blood cells leads to the release of heme and other catabolites. Heme is the prosthetic group of hemoproteins found in red blood cells. It contains an iron ion (Fe2+) held within a heterocyclic organic ring known as a porphyrin Address all correspondence to Manasi Chavan at manasi.chavan@basf.com.

JOURNAL OF COSMETIC SCIENCE 104 (Figure 1). Under normal conditions, heme is intact within hemoproteins, but can be released under oxidative stress and became free heme. The free heme produced in this manner is highly cytotoxic, most probably due to the iron atom contained within its porphyrin ring, which can undergo Fenton chemistry to catalyze production of free radi- cals in an uncontrolled manner (2). This property of free heme can also sensitize a variety of cell types to undergo programmed cell death in response to proinfl ammatory stimuli. This deleterious effect is thought to play an important role in the pathogenesis of certain infl ammatory diseases (3). When the infl ammation occurs around the eyes, it can, in turn, exacerbate further blood leakage. This downward spiral will cause negative effects in the eye area including the formation of dark circles. Therefore, it is critical to scavenge and dispose of free heme as quickly as possible. Heme is degraded by an essential enzyme called heme oxygenase (HO) to carbon monox- ide, iron and biliverdin, which is subsequently converted to bilirubin by biliverdin re- ductase (Figure 2). Research has shown that carbon monoxide at low concentrations can act as an endogenous mediator of cellular signaling, and has antioxidation, anti-infl ammation and antiapoptotic activities (4). The iron produced by the degradation of heme is seques- tered in ferritin. Bilirubin, and biliverdin are also very good antioxidants (5,6). Thus HO turns free heme, a very toxic molecule, into several cytoprotective products. Figure 1. Heme. Figure 2. Heme catabolites and their properties.