Effect of Oligopin® on Skin Ageing

Extrinsic or exogenous ageing is caused by repetitive exposure of the skin to harmful agents, while primary cause the exposure to ultraviolet (UV) radiation, known as photoageing, including solar effect. Chronic solar UV exposure has multiple damaging effects on skin, such as wrinkling, dryness, dyspigmentation, epidermal thinning and increasing fragility. In addition, solar exposure and age increase a subepidermal band. Fibrillar collagen, which is synthesized from fibroblasts, is the predominant extracellular matrix (ECM) component of the dermis. Collagen type I and III are considered to be the major interstitial, fiber forming collagen in normal human dermis. In addition, the dermis contains collagen types IV (gelatine), V and VI. Other important component of the EMC of the dermis are elastic fibers being elastin (ELN) their main component and play a critical role in skin elasticity and the reduction of elastic fiber production results in impaired elasticity. UV radiation induces ECM degeneration and consequently an increase in fragility and loss of elasticity of the skin. This process is mediated by an increase in matrix metalloproteinases (MMPs) expression in human skin which are responsible for degrading ECM proteins, such as collagen, fibronectin and elastin. The natural inhibitors of MMPs are tissue inhibitors of metalloproteinases (TIMPs), being TIMP-1 the most relevant TIMP affecting collagen metabolism.

Orally administered ingredients can have positive effects on skin characteristics by modulating the internal factors leading to the changes associated with photoageing. Thus, the use of food ingredients and supplements that claim to reduce the risk of skin disorders or alleviate skin ageing is increasing. Between these ingredients, polyphenols obtained from botanical extracts has been used for cosmetic applications, including Pycnogenol®, a French Maritime Pine Bark extract (FMPBE). showing photoprotective effect against UV-light induced skin damages, and an improvement in hydratation and elasticity of skin in human clinical trials. In another clinical trial, treatment with a different FMPBE called Flavangenol®, significantly decreased skin photo-aged scores. Other human intervention studies with oral administration of polyphenol extracts of different origins such as citrus extract (NutroxSun®), red orange fruit extract (Red Orange Complex®), Polypodium leucotomos and Pomegranate extracts (PPmix® and Fernblock®) have demonstrated beneficials effects of these supplements on improvement of skin characteristics. The results of the studies cited above suggest that oral administration of polyphenols rich extracts and especially of FMPBE is a promising approach for nutritional photoprotection of skin, reducing photoageing. Nevertheless, it must be taken into account that most of these studies have been done with a low number of subjects, with combination with other ingredients and/or without placebo group. Thus, well designed clinical trials with a correct volunteer's number are required to obtain robust results about the effects of FMPBE on skin ageing. Dérivés Résiniques et Terpéniques (DRT) is a company that has developed and commercialize Oligopin®, a polyphenol extract derived from French maritime pine bark. Oligopin® is characterized by a practical absence of tannins ( \< 1%) and a high content in low molecular weight oligomeric procyanidins (OPC \> 70%; dimers about 20%), a distinctive feature of other proanthocyanidin-rich extracts such as Pycnogenol® which contained about 5% of dimers. Furthermore, although the insoluble products in water are low in both products, lower and more adequate concentrations are present in Oligopin® (Oligopin ® typically 2 to 4% to a maximum at 5% versus Pycnogenol®: 6% - 8.1%). The degree of polymerization of OPC can determine its absorption across cell membranes and, as it has been observed in rats, only a certain OPC of a lower degree of polymerization is absorbed during transit in the gut. Consequently, the effect of FMPB extract could be determined, in part, by the quality of its OPC. The hypothesis of the present study is that circulating metabolic fraction of Oligopin® might exert beneficial actions on collagen metabolism, which is directly linked to skin strength and elasticity. In consequence, the daily consumption of Oligopin® will exert beneficial effects on skin ageing through the modulation of the proteins involved in the metabolism of collagen in humans. The main objective of the study is to determine the beneficial effects of Oligopin® on skin aging, through the improvement of skin elasticity in participants with photo-aging. The secondary objectives of the study are: * To evaluate the effects of Oligopin® on skin aging through the measurement of wrinkles, spots, skin hydration and subepidermal band. * To evaluate the effects of Oligopin® on the dynamics of collagen and elastin through the determination of different biomarkers in serum and the expression of genes in peripheral blood mononuclear cells (PBMCs). * To discover new biomarkers of the effects of Oligopin® through transcriptomic analysis in PBMCs and serum metabolomic analysis. * To characterize the metabolites of Oligopin® (MFO) in plasma. * To establish potential correlations between specific metabolites of MFO and the beneficial effects of Oligopin® on the skin, as well as between serum biomarkers and PBMC. * To evaluate the ability of the MFO to modulate the dynamics of collagen through the use of cellular models of human fibroblasts. In an initial phase, an acute postprandial study will be carried out with 20 of the 60 volunteers with the consumption of 700 mg of Oligopin® in a single day, with the aim of obtaining the MFO. With MFO, the mechanisms by which Oligopin® exerts the beneficial effects on skin aging will be studied through in vitro studies with cellular models. The 60 participants will participate in the second phase of the study, which will be randomly divided into two groups of 30 participants, depending on whether they consume a 100 mg Oligopin® capsule or a placebo capsule, with the same appearance as the Oligopin® capsule but will not contain the botanical extract. In this second phase, participants will consume one capsule each day for a total of 6 weeks. During the study there will be 5 visits, one of selection (V0), one of the first phase of the study (V1; week 1) and 3 visits of the second phase of the study (V2, V3 and V4; weeks 2, 3 and 4).