title: Neuroimmunomodulatory compound for sensitive skin care: in vitro and clinical assessment.
abstract: BACKGROUND
  The pathophysiology of sensitive skin consists of an inflammatory reaction resulting from the abnormal penetration in the skin of potentially irritating substances, which occurs due to skin barrier dysfunction and changes in the production of local neuromediators.
  
  
  OBJECTIVE
  The therapeutic potential of L-carnosine and Rhodiola rosea, as antioxidant and neuromodulatory, respectively, leads us to investigate the effects of the R. rosea extract/L-carnosine-associated compound (RCAC) on sensitive skin alterations.
  
  
  METHODS
  A double-blind comparative study was conducted on 124 volunteers with sensitive skin, who were selected by their reactivity to stinging test. Two randomized groups of 62 each received either a formulation containing 1% of RCAC or placebo, which was applied twice a day for 28 consecutive days. One perceptibility questionnaire was applied at the onset and at the end of the treatment to evaluate the subjective response to test product. Additionally, in vitro studies were performed to investigate RCAC neuroimmunomodulatory mechanisms.
  
  
  RESULTS
  RCAC treatment produced in vivo protective effects in skin barrier function and a positive subjective response of sensitive skin volunteers. In vitro treatment promoted the release of proopiomelanocortin peptides and restored to normal the increased levels of neuropeptides and cytokines produced by keratinocytes exposed to ultraviolet radiation. Clinical effectiveness was measured by reduction of transepidermal water loss, positive perceptions of improvements in skin dryness and skin comfort sensation, and reduction of discomfort sensation after stinging test.
  
  
  CONCLUSIONS
  The protective effect of RCAC in skin barrier function and the positive response produced in human subjects with sensitive skin could be partially explained by our in vitro results showing a significant increase in opioid peptides release, an inhibitory effect on neuropeptides production, and modulation of cytokines production by keratinocytes under ultraviolet stress.
authors.affiliation: Department of Pharmacology/Hemocenter, Faculty of Medical Science, State University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Gustavo de Campos
authors.initials: Gde C
authors.lastname: Dieamant
authors.forename: Maria Del Carmen
authors.initials: Mdel C
authors.lastname: Velazquez Pereda
authors.forename: Samara
authors.initials: S
authors.lastname: Eberlin
authors.forename: Cecília
authors.initials: C
authors.lastname: Nogueira
authors.forename: Rejane Maria
authors.initials: RM
authors.lastname: Werka
authors.forename: Mary Luci de Souza
authors.initials: ML
authors.lastname: Queiroz
mesh_terms: D000279:Administration, Cutaneous; D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002336:Carnosine / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D004745:Enkephalins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008875:Middle Aged; D018373:Peripheral Nervous System Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D029771:Rhodiola; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D011795:Surveys and Questionnaires; D014466:Ultraviolet Rays; D014870:Water Loss, Insensible / Q000187:drug effects; D001615:beta-Endorphin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D004745:Enkephalins; D018373:Peripheral Nervous System Agents; D010936:Plant Extracts; D013373:Substance P; D001615:beta-Endorphin; D002336:Carnosine; D015740:Calcitonin Gene-Related Peptide