J. Cosmet. Sci., 62, 305–316 (May/June 2011) 305 Evaluation of anti-cellulite effi cacy: A topical cosmetic treatment for cellulite blemishes—A multifunctional formulation ADELE SPARAVIGNA, GIANCARLO GUGLIELMINI, STEFANO TOGNI, ALDO CRISTONI, and GIADA MARAMALDI, Derming, Monza (MB) (A.S.), Sinerga, Pero (MI) (G.G.), and Indena, Milan, (S.T., A.C., G.M.), Italy. Synopsis Cellulite is thought to affect 80-90% of postpubertal women, and is considered much of a cosmetic concern by the large majority of them. In this study, the objective was to assess the effi cacy of a topical cosmetic product containing various active ingredients of botanical origin on cellulite blemishes on female volunteers affected by fat accumulations, as well as by slight-to-moderate cellulite in the lower limbs. The assessment was performed by means of various objective evaluations, including contact thermography, morphometric measures of thigh circumference, and microcirculation evaluation. The obtained results indicate that the use of synergistic botanical standardized extracts, through the exploitation of different mechanisms of action and acting on different biological targets, provides visible and measurable results in the improvement of cellulite signs and symptoms. INTRODUCTION Cellulite onset and recognition as a real pathology is still controversial, as well as its exact causes. On the one hand, it has been recently described as a physiological condition aimed to maximize adipose retention in order to ensure adequate caloric availability during pregnancy and lactation (1), but cellulite is also a complex problem, involving several different factors and mechanisms, such as metabolic imbalances, alterations in connective tissue structure, genetic factors, infl ammatory conditions, reduced microcirculation, and hormonal factors. Although genetic predisposition to cellulite has been related to a par- ticular polymorphism in the angiotensin-converting enzyme and hypoxia-inducible fac- tor 1A genes (2), diet and lifestyle also play an important role in the improvement or worsening of the aspect of cellulitic areas. From a metabolic standpoint, during the onset of cellulite, adipocytes become engorged with lipids and cluster together while an excess of subcutaneous fl uids is retained. Also, Address all correspondence to Giada Maramaldi at Giada.maramaldi@indena.com Stefano Togni, Aldo Cristoni, and Giada Maramaldi work at Indena SpA, the company that produces the active ingredients used in the trail. Giancarlo Guglielmini works at Sinerga SpA, the company that manufac- tured the batches of active treatment and placebo used in the trial.

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