39th Annual ESDR Meeting, Budapest, Hungary

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1 39th Annual ESDR Meeting, Budapest, Hungary Inhibition of Apoptosis-Driven Regression of Hair Bulb Giuliani G1, Benedusi A1, Marzani B1, Carelli S2, Traversa M2, Di Giulio A2, Gorio A2 1 Giuliani SPA, Milan, Italy 2 Laboratories of Pharmacology, Dept. Medicine, Surgery and Dentistry, University of Milan, Italy Hair exerts a range of functions including thermoregulation, physical protection, sensory activity. Mature and actively growing hair follicles become anchored in the subcutis, and regenerate by spontaneous repetitive cycles of growth (anagen), apoptosis-driven regression (catagen), and quiescence (telogen). HF regression is characterized by activation of pathways that induce apoptosis in HF cells. We focused our study on investigating the effect of new therapeutic molecules capable of counteracting the regression phase. HFDPC cells, grown in culture, were incubated for 24 hours incubation with 1 μμ staurosporin and apoptosis was monitored. There was a marked activation of Caspase-3 accompanied by cytoskeletal degradation, nuclear blebbing, and cellular fragmentation. The addition of spermidin or rutine in the micromolar range concentration reduced staurosporininduced caspase activity by over 50%, when the two agents were added simultaneously equal levels of caspase-3 inhibition was achieved with concentration 10 fold lower. Zeaxantine alone was ineffective, however when added to the combined spermidin and rutine treatment, the staurosporin-induced caspase activity was almost totally counteracted and the enzymatic activity was significantly reduced. These combined treatment were also effective in preventing staurosporinmediated cellular damage. The extent of cell loss was greatly reduced with preservation of cell shape and actin-tubulin cytoskeleton. The combined treatment also counteracted staurosporininduced caspase-3 and PARP over-expression, and prevented the inhibition of Akt/PKB and MAP kinase ERK1/2 activities. The protective effects of our agents was also observed in ex vivo bulbs. After 24 hours in vitro culture of bulbs there is a dramatic loss of Akt and ERK phosphorylation. This is totally prevented by coincubation with our combined treatment. Thus, here we report that concomitant exposure of spermidine, rutine and zeaxantine blocks the degradation of vital intracellular pathways and structure of vital importance for the prevention of catagen.

2 69th Annual Meeting, May 6-9, 2009 in Montreal. A novel anti-catagen formulation G Giuliani, 1 B Marzani, 1 A Benedusi, 1 M Traversa, 2 S Carelli, 2 A Gorio 2 and F Rinaldi3 1 R&D, Giuliani S.p.A., Milan, Italy, 2 Laboratories of Pharmacology, Dept. Medicine, Surgery and Dentistry, University of Milan, Milan, Italy and 3 Studio Rinaldi, Milan, Italy The life cycle of the hair bulb can be reduced to three phases: anagen, catagen and telogen. We are mostly interested in developing therapeutic strategies capable of counteracting the regression phase (catagen), that is mostly caused by apoptosis of epithelial and melanocyte cells. We have tested our working hypothesis on HFDPC-c cells, grown in culture in the Follicle Dermal Papilla Growth Medium, and apoptosis was induced by 24 hours incubation with 1 Μ staurosporin. This treatment resulted in a marked activation of Caspase-3 accompanied by cytoskeletal degradation, nuclear blebbing and cellular fragmentation. The addition of spermidine or rutine in the micromolar range concentration reduced staurosporin-induced caspase activity by over 50%, when the two agents were added simultaneously the same extent of caspase-3 inhibition was achieved with concentration 10 fold lower. Zeaxanthine alone was rather ineffective, however when it was added to the combined treatment, made by spermidine and rutine, the staurosporin-induced caspase activity was almost totally counteracted and the enzymatic activity was much more significantly reduced. These combined treatment was also very effective in preventing staurosporin-mediated cellular damage. The extent of cell loss was greatly reduced, and, differently from untreated cells, there was a total preservation and normal distribution of actin-tubulin cytoskeleton with normal cellular shape. Interestingly, our combined treatment counteracted also the over-expression of caspase- 3 induced by staurosporin. In conclusion, this novel formulation may pride an effective preventing treatment for the catagen phase of the hair bulb life cycle.

3 IN PRESS Journal of Plastic Dermatology 2009 Efficacy of spermidine in the treatment of hair loss. Double blind clinical trial placebo controlled in vivo and ex vivo by confocal microscopy F. Rinaldi, * G. Giuliani, P. Bezzola, and E. Sorbellini International Hair Research Foundation (IHRF), Milan, Italy Rinaldi Dermatologic Clinic, Milan, Italy * R e D Giuliani S.p.A, Milan, Italy

4 NUTRAfoods (1) 1-7 BIOGENINA BASED FOOD-SUPPLEMENT: hair growth enhancer Fabio Rinaldi, Elisabetta Sorbellini, Paola Bezzola Dermatologic Dept, Policlinico Multimedia-Milano Danila Ingrid Marchioretto Giuliani - Milan

5 Integr Nutr 2002, 5(4) INTEGRATORE DIETETICO A BASE DI BIOGENINA Stimolazione della Crescita del Fusto dei Capelli Fabio Rinaldi, Elisabetta Sorbellini, Paola Bezzola Unità Operativa di Dermatologia, Policlinico Multimedica - Milano Danila Ingrid Marchioretto Giuliani - Milano