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Discovery of novel 11β-HSD1 inhibitors with potential skin care applications

corresponding

Eileen Jackson*, Dominik Imfeld, Eliane Wandeler, Remo Campiche, Piero Geotti-Bianchini
*Corresponding author
DSM Nutritional Products, R&D Personal Care, Kaiseraugst, Switzerland

Abstract

Increased cortisol levels in skin appear to be a major driver for collagen atrophy and reduced cell proliferation. One major pathway of cortisol synthesis in the skin is the activation of the enzyme
11β-HSD1, which is expressed in skin cells. We therefore developed novel 11β-HSD1 inhibitors and investigated their effects on skin in vitro and ex vivo. We demonstrated that 11β-HSD1 inhibitors can reverse morphological changes in the skin caused by cortisone application or UV exposure, presumably through the 11β-HSD1 pathway. Since 11β-HSD1 excess in aged and photodamaged skin may play a role in age-induced skin atrophy, reversing the excess activity of this enzyme represents an attractive novel anti-aging strategy for cosmetic applications.


INTRODUCTION                                                                                             

Skin, the body’s largest organ, is our primary defence against environmental factors, such as heat, ultraviolet (UV) light irradiation, and pollution. Over time the aging process starts to manifest in our skin in the form of wrinkles, age spots and grey hairs (1). Two different types of aging have been defined: intrinsic aging, due to genetic or hormonal alterations as the result of time, and extrinsic aging, caused by environmental factors, such as exposure to UV radiation, air pollution and others. It has been recognized that extrinsic aging is by far the most influential factor, and within this category sun exposure has been reported to account for 80% of facial aging.

Major alterations of aged skin appear to be localized in the dermal extracellular matrix (ECM) (2). While young skin is characterised by abundant, tightly packed, well-organised collagen fibres, aged skin exhibits fragmented and disorganised collagen fibres. Aged, thin, fragile sk ...




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