DANIEL SCHMID*, RIIKKA SACHER, ESTHER BELSER, FRED ZÜLLI
*Corresponding author
Mibelle Biochemistry, Bolimattstrasse 1, Buchs, 5033, Switzerland

Abstract

Chronologically aged skin is characterized by a diminished expression of growth factors. The consequence is a reduced biosynthesis of matrix proteins such as collagen and elastin. These alterations in the extracellular matrix network occur in the dermis, a skin tissue that cannot be easily reached by topically applied cosmetic actives. A strategy for medication of the aging dermis by cosmetic treatments could be to utilize the communication processes between the cells of the outer skin layer, the epidermis, and the cells of the subjacent dermis. Communication is normally mediated by growth factors and cytokines released by one sort of cells that reach other cell types by diffusion. In a series of cell culture assays, an extract of crocus bulbs was shown to stimulate epidermal keratinocyte cells to release growth factors into the medium. The cell-free medium incubated with dermal fibroblast cells was found to enhance the expression of elastin, of the elastin-processing enzyme lysyl oxidase-like 2 and of the connective tissue growth factor (CTGF). Exactly the same expression pattern was obtained by treating fibroblast cells with TGF-β. The crocus bulb extract directly applied to fibroblast cells was without effect. The results clearly demonstrated that the crocus bulb extract induced secretion of messenger compounds in the epidermis that could enhance the synthesis of matrix proteins in the dermis. The in vitro results were confirmed in clinical trials with a cream containing the crocus bulb extract. Analysis of skin collagen and elastin with the non-invasive two-photon microscopy could demonstrate a clear augmentation of both of these skin structure components. In another clinical study with twenty test persons, there was a clear, placebo-controlled increase in skin firmness and elasticity after 4 weeks’ application.

INTRODUCTION

Growth factors and cytokines are messenger compounds, in most cases proteins, that allow the communication between cells in our tissues. After binding to specific receptors on cell surfaces, growth factors activate cellular proliferation or differentiation. In the skin, growth factors orchestrate the wound-healing process (1) and also the continuous regeneration and repair. The repair of skin damaged by a wound or after UV exposure takes place in two phases. Firstly there is an inflammatory reaction. Activation of the NF-AB pathway in the cells of the epidermis leads to the formation of inflammatory cytokines such as IL-1, IL-8 and TNF-α (2). These inflammatory messengers activate in the subjacent dermis the synthesis of proteolytic enzymes that start to degrade the extracellular matrix composed of collagen and elastin fibres. After cleaning of the damaged skin area, the inflammatory phase stops and the skin regeneration phase starts with the release of growth factors such as TGF-β. Enhancement of extracellular matrix production is a major effect of TGF-β. In intrinsic skin aging there is no inflammatory phase but the enhanced formation o ...