Claudia Mundt

Novel Aspects of Intrinsic and Extrinsic Aging of Human Skin: Beneficial Effects of Soy Extract¶

Abstract Biochemical and structural changes of the dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase-1 are expressed differentially, indicating UV-mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV-mediated increase in hyaluronan (HA) levels. To counteract these age-dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo-controlled in vivo study, topical application of an isoflavone-containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal–epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin.

Anti-inflammatory efficacy of licochalcone a : correlation of clinical potency and in vitro effects

Licochalcone A (LicA), a major phenolic constituent of the licorice species Glycyrrhiza inflata, has recently been reported to have anti-inflammatory as well as anti-microbial effects. These anti-inflammatory properties might be exploited for topical applications of LicA. We conducted prospective randomized vehicle-controlled clinical trials to assess the anti-irritative efficacy of cosmetic formulations containing LicA in a post-shaving skin irritation model and on UV-induced erythema formation. The clinical trials were accompanied by a series of in vitro experiments to characterize anti-inflammatory properties of LicA on several dermatologically relevant cell types. Topical LicA causes a highly significant reduction in erythema relative to the vehicle control in both the shave- and UV-induced erythema tests, demonstrating the anti-irritative properties of LicA. Furthermore, LicA is a potent inhibitor of pro-inflammatory in vitro responses, including N-formyl-MET-LEU-PHE (fMLP)- or zymosan-induced oxidative burst of granulocytes, UVB-induced PGE2 release by keratinocytes, lipopolysaccharide (LPS)-induced PGE2 release by adult dermal fibroblasts, fMLP-induced LTB4 release by granulocytes, and LPS-induced IL-6/TNF-α secretion by monocyte-derived dendritic cells. The reported data suggest therapeutic skin care benefits from LicA when applied to sensitive or irritated skin.

MODULATION DES OXIDATIVEN STRESSES IN DER HUMANEN ALTERSHAUT

Zusammenfassung Oxidativer Streß (UV-Licht, freie Radikale) ist einer der wesentlichen Auslöser für vorzeitige Hautalterung. Als aktive Schutzmechanismen gegen diese oxidativen Schäden, die besonders im Alter zunehmen, können Koenzym Q10 (CoQ10), aber auch exogen applizierte Antioxidanzien wirken.Unsere vergleichenden In-vitro- und In-vivo-Untersuchungen an Haut alter Probanden zeigen anhand der Meßparameter (ultraschwache Photonenemission, Gesamtthiolstatus, Mitochondrienmembranpotential und Zellvitalität), daß die endogene Resistenz gegen UV-Licht in Keratinozyten alter Spender reduziert ist. Diese geringere Resistenz, d.h. der schlechtere Schutz der epidermalen Zellen gegen oxidative Stressoren, insbesondere gegen UV-Licht, kann durch topische Applikation von Verbindungen wie CoQ10 und Antioxidanzien wie alpha-Glucosylrutin (15) deutlich verbessert werden. Placebokontrollierte In-vivo-Studien zeigen außerdem, daß bereits vorhandene, vornehmlich durch Lichtalterung (Photoaging) bedingte Hautveränderungen, wie z.B. sichtbare Fältchen im Bereich der Augenwinkel, durch topische Langzeitbehandlung mit humanidentischem CoQ10 deutlich reduziert werden können.Summary Oxidative stress (UV irradiation, free radicals) plays a significant role in aging. Coenzyme Q10 (CoQ10) and exogenously applied antioxidants can significantly reduce the formation of oxidative stress with increasing age.In our in vitro and in vivo experiments concerning the parameters of ultraweak photon emission (UPE), intracellular thiol status, mitochondrial membrane potential and cell vitality, we demonstrated a diminished resistance in keratinocytes of old donors against UV irradiation. This reduced epidermal resistance against oxidative stressors, i.e. UV irradiation, can be improved by topical application of CoQ10 and antioxidants like alpha-glucosylrutin (15). Furthermore, our in vivo investigations show that wrinkles around the region of the eyes (“crow feet”) could be reduced by long-term application of CoQ10.

Complex formation of sericoside with hydrophilic cyclodextrins: improvement of solubility and skin penetration in topical emulsion based formulations

The main objective of this study was to devise novel methods for improving the solubility of the anti-inflammatory triterpenoid sericoside, the main component of Terminalia sericea extract, thus enabling its incorporation into topical formulations. Sericoside was stabilized by complex formation with hydrophilic derivatives of beta- and gamma-cyclodextrins in a molar ratio of 1.0:1.1. The complex of extract and cyclodextrin was equilibrated in water at 25 degrees C for approximately 24 h. The dehydrated complexes of T. sericea extract and cyclodextrin were characterized by differential scanning calorimetry, thermogravimetry analysis and X-ray diffraction. Complex formation with beta-cyclodextrin as well as gamma-cyclodextrin derivatives was detectable using these three analytical tools; however, only complexes with gamma-cyclodextrin derivatives showed stability upon storage after incorporation into topical o/w or w/o formulations. Furthermore, a T. sericea extract/gamma-cyclodextrin complex incorporated in an o/w formulation resulted in a 2.6-fold higher percutaneous penetration of sericoside in in vitro excised pig skin as compared to pure T. sericea extract. For the first time, the virtually insoluble anti-inflammatory active sericoside was incorporated into a topical emulsion based formulation in a stable manner, resulting in efficient skin penetration.