Crocus bulb extract prompts epidermis/dermis crosstalk

The messenger molecules involved are mainly cytokines and growth factors. An imbalance in the synthesis and release of these signals as it is observed in elderly skin may lead to a reduced biosynthesis of important extracellular-matrix (ECM) proteins such as collagen and elastin. Here we present a strategy to activate matrix protein production by stimulating growth factor synthesis and release by keratinocytes, which can easily be reached by superficially applied cosmetic compounds. In vitro assays demonstrate that a crocus bulb extract can activate expression of elastin, lysyl oxidase-like 2 enzyme (LOXL2) and the connective tissue growth factor (CTGF). Non-invasive skin structure analysis by two-photon microscopy performed after a two-week treatment with a cream containing the crocus bulb extract demonstrates a clear augmentation of collagen and elastin.

 Interactions between growth factors, skin cells and the extra-cellular matrix (ECM) are essential for tissue regeneration in wound healing1 as well as intrinsic ageing of the skin. Wound healing is a complex process comprising different phases such as inflammation, proliferation and remodelling, all of which require growth factors to regulate the fine balance between the synthesis of extracellular matrix and its degradation by proteases.2 Intrinsic skin ageing is accompanied by an accumulation of reactive oxygen species (ROS) due to an impaired mitochondrial oxidative metabolism. Enhanced ROS formation will affect cell signalling pathways which lead to an increased break down of extracellular matrix components.3 The thinning and fragility of elderly skin is the result of an imbalance of degradation and regeneration of skin tissue. More recently, studies by Quan and colleagues find an additional reason for the loss of matrix structure in a decreased synthesis and release of growth factors.4 Specifically this work suggests that a decrease in the growth factors CTGF and transforming growth factor-(TGF-) in aged skin and fibroblasts leads to a decrease in the expression of extracellular structural proteins. CTGF is primarily induced by TGF-and appears to function as a down-stream mediator in the activation of extracellular matrix synthesis. Therefore one might ask: could ageing skin be rejuvenated by supplementing growth factors? The use of natural human growth factors in cosmetic products is prohibited. Biotechnologically-produced growth factors could theoretically be used for cosmetic products, but their efficacy is very limited for the following reasons: most growth factors are proteins of high molecular weight and complex conformation, which reach a limited penetration depth into the skin. Moreover, growth factors were shown to be unstable in cosmetic formulations, they lose their functionality and are quickly degraded by proteases following superficial application. Here we describe an approach to stimulate the growth factor-dependent synthesis of matrix proteins in the dermis by improving keratinocyte-fibroblast communication. In the present study we investigated the effect of specific plant bulb extracts on human keratinocyte cell cultures for the purpose of enhancing the synthesis and release of growth factors, which stimulate fibroblast cells to synthesise extracellular matrix proteins. In a plant the bulb serves as a food reserve in order to support the newly growing plant with nutrients. We identified a bulb extract from Crocus chrysanthus with the ability to activate intercellular communication.

Materials and methods