JOURNAL OF COSMETIC SCIENCE 306 infl ammation of connective tissue and degradation of connective fi bers occur. The subcutane- ous adipose layer appears to be much thicker in women with cellulite compared to women devoid of cellulite (3). Also there are peculiarities in the architecture of fi brous septae compartmentalizing the adipose tissue, these being much more abundant in women af- fected by cellulite than in men, typically not affected by this disorder. Regardless of the number of women affected by cellulite, only a limited number of studies have been pub- lished in the scientifi c literature so far, botanical derivatives being one of the main groups of evaluated compounds for its treatment. A multi-target/multi-component strategy has been recently recognized as one of the best approaches to counteract the main cellulitic symptoms and signs (4). The botanical kingdom may offer several active ingredients, mainly in the form of standardized botanical extracts, able to act synergistically on differ- ent biological targets and to improve these sign and symptoms. Other crucial aspects not to be forgotten in cellulite treatment are represented by circulation in the lymphatic and venous systems and by capillary integrity. The aim of this study was to evaluate the cos- metic effi cacy of a topical product on several cellulite signs and symptoms. The topical product (Formulation code: ACTIVE—anticellulite cream) contains a blend of botanical ingredients that, in different approaches and with different mechanisms of action, are intended to counteract cellulite at different levels. The active ingredients selected are: Visnadine. Visnadine is a pure molecule extracted from the seeds and aerial part of • Ammi visnaga, a plant widely used in Egyptian traditional medicine as an antispastic and vasodilator. It has shown anti-phosphodiesterase activity, maintaining elevated levels of cAMP and thus increasing lipase activity (5), which suggests a cosmetic application in the treatment of localized fatty deposits and cellulite. Pharmacological evidence consistent with traditional use has underlined a strong vascular activity of visnadine both on great and medium-size vessels (6). Visnadine also acts on peripheral vessels, inducing persistent vasokinetic activity with positive inotropic effects (7). In some previous experiences, the vasomotor activity of visnadine was assessed through the measurement of skin temperature by contact thermography and laser Doppler fl owmetry (8). The topical application of this active ingredient is then reasonable in the treatment of peripheral vessel disorders. The well-documented phosphodiesterase-inhibiting activity of visnadine, combined with the relevant microcirculatory effects, suggests its potential application in the treatment of panniculopathies of the lower limbs. Ginkgo biloba • Dimeric Flavonoids Phytosome®. Whereas Ginkgo biloba is being used worldwide as an herbal medicine for various circulatory disorders, the bifl avonic fraction obtained from Ginkgo biloba leaf was shown to decrease cAMP phosphodiesterase and to increase microcirculation (9). Lipolysis stimulation was assessed in vitro, whereas blood fl ow improvement was evaluated in subjects affected by cellulite, and the evaluation comprised blood fl ow and capillary density objective measurements (10). The bifl avonic fraction of Ginkgo biloba has been complexed with soy phospholipids to obtain the Phytosome® complex, a technology used to improve the topical bioavailability and effi cacy of botanical extracts (11). Escin. Escin is a natural mixture of triterpene saponins obtained from the seeds of • Aesculus hippocastanum (horse chestnut). Horse chestnut seed and leaf were traditionally used to treat varicose veins, hemorrhoids, and phlebitis, due to the activity of escin, which was shown to modulate vascular exchanges at a peripheral level, strengthening

EVALUATION OF ANTI-CELLULITE EFFICACY 307 the capillary wall and preventing fl uid leakage (12). The pharmacological activity is then a decrease in capillary permeability, and an anti-edema effi cacy is observed. Escin also possesses signifi cant anti-infl ammatory properties, which can, however, be hardly separated from the anti-edema effi cacy on pharmacological models. The combination of the mechanisms of action identifi ed so far appoints escin as a relevant active ingredient in the treatment of cellulite. MATERIALS AND METHODS FORMULATION The formulation of the topical product (ACTIVE) was developed with Sinerga Research Center Laboratories (Pero, Italy). The development took into account not only the effi cacy of the active substances to counteract the causes of cellulite blemishes, but also the pleas- antness of the fi nal formulation in order to achieve the best possible compliance. The botanical active ingredients formulated in ACTIVE are visnadine (0.25% w/w), Ginkgo biloba Dimeric Flavonoids Phytosome®(0.5% w/w), and escin (1% w/w). The association of these active ingredients (described in patent WO2005/004858) has been selected accord- ing to the specifi c profi le of each single substance. TRIAL DESIGN The aim of the study was to clinically assess the cosmetic effi cacy of a topical treatment to be applied on the thighs over a period of four weeks. Morphometric analysis and in- strumental evaluations were carried out. Twenty-fi ve female volunteers (ages: 30–55 yrs), affected by fat accumulations and/or slight-to-moderate edematous-fi brosclerotic pan- niculopathy in the lower limbs, were selected for the study. The multifunctional product ACTIVE, containing the botanical ingredients visnadine (0.25%), Ginkgo biloba Dimeric Flavonoids Phytosome® (0.5%), and escin (1%) (obtained from Indena S.p.A., Italy), was compared to its relevant placebo formulation PLACEBO. All volunteers provided a writ- ten informed consent. The trial was conducted in a single-blind method with the com- parison within subjects (each subject being its own control), and volunteers were required to apply the test products on the thigh twice a day, unilaterally, for a period of four con- secutive weeks. They underwent two medical examinations, a baseline evaluation at T0 before the beginning of the test, and an evaluation at the end of the treatment period T4. Body weight, in the case of substantial differences between the beginning and the end of the trial, was considered as a dropout criterion. However, no dropouts due to relevant body-weight variations occurred (during the course of the study, the two dropouts quit the trial due to personal reasons independent from the trial itself). Additionally, at the beginning of the treatment, the overall tolerability of the treatment was also observed. Finally, the effi cacy of the treatment was assessed both clinically and instrumentally. CLINICAL EVALUATION The clinical assessment was carried out at the upper, median and lower third of the thigh, according to the following evaluations: