Abstract:With the public's growing interest in skin whitening, lightening ingredients only used under dermatological supervision until recently, are more and more frequently incorporated into cosmetic formulas. The active agents that lighten skin tone are either natural or synthetic substances, and may act at various levels of melanogenesis. They are used to treat various skin pigmentation disorders or simply to obtain a lighter skin tone as whiter skin may be synonymous of wealth, health, youth, and/or beauty in different cultures. However, recent studies demonstrated the adverse effects of some of these ingredients, leading to their interdiction or restricted use under the European Directive and several other international regulations. After an overview of skin whitening practices and the associated risks, this article provides insight into the mechanisms involved in melanin synthesis and the biological assays available to attest the lightening activity of individual ingredients. The legislation dealing with the use of skin lighteners is then discussed. As traditional depigmenting agents such as hydroquinone and corticosteroids are of safety concern, the potential of natural extracts has been investigated more and more; finally, a synthesis of three years of research in our laboratory for such plant extracts will be given.

Lipodystrophic syndrome is a major side effect of highly active antiviral therapy. Fat tissue redistribution is associated with changes in adipocyte gene expression and in circulating levels of adipocytokines involved in the development of insulin resistance. However, the evidence that HIV drugs accumulate into human adipocytes and have a direct effect on the expression of adipocyte-specific genes is still lacking. To address these questions, we used adipocytes derived from adult stem (hMADS) cells isolated from human adipose tissue. We showed by ELISA that two inhibitors of the HIV protease, lopinavir and ritonavir, accumulated at similar levels during the development of hMADS cells in adipocytes, whereas a non-nucleoside reverse transcriptase inhibitor, the nevirapine, accumulated at lower levels. Two fluorescent protease inhibitors then have been generated to investigate their subcellular localization. The data showed that HIV drugs accumulated into adipocytes and displayed various effects on hMADS cell-derived adipocytes. Indinavir, amprenavir, and nevirapine did not alter differentiation of precursor cells. In contrast, lopinavir, saquinavir, and ritonavir inhibited the development of preadipocytes into adipocytes. In adipocytes, amprenavir increased leptin expression and ritonavir was able to up-regulate tumor necrosis factor-␣, interleukin 6, and leptin expression and downregulate the expression of peroxisome proliferatoractivated receptor ␥ and adiponectin. Intracellular accumulation and localization of HIV drugs into human adipocytes strongly suggest that adipose tissues store these drugs. Because ritonavir can alter the expression of insulin resistance-related cytokines in human adipocytes in a way parallel to the situation observed in vivo upon treatment of HIV-infected patients, we propose that protease inhibitors participate in insulin resistance through a direct effect on adipocytes.Highly active antiretroviral therapy (HAART) 1 combines treatment with three classes of anti-HIV drugs: 1) protease inhibitors (PIs); nucleoside reverse transcriptase inhibitors (NRTIs); and non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs have demonstrated their efficiency in improving the lifespan of HIV-infected patients. However, patients under HAART develop metabolic alterations including fat tissue redistribution with peripheral lipoatrophy and increased central adiposity. The lipodystrophic syndrome affects up to 60% treated HIV-infected patients and is emerging as a significant medical concern (1). The adipose tissue of lipodystrophic HIV-infected patients contains clusters of small adipocytes (2) that can result from a defect in differentiation of adipocyte precursors or from metabolic alterations of mature adipocytes. PIs and NNRTIs were detected in adipose tissue of patients, but evidence that HIV drugs accumulate and have a direct effect on the development of human adipocytes are still lacking. It has been recently shown that PIs can enter and accumulate in cultured mouse adipocytes (3, ...