Substancefor Restoring Normal Co-expression and Interaction Between the LOX and NRAGE Proteins

Abstract

The invention relates to a substance for restoring normal co-expression and interaction between the LOX and NRAGE proteins. The invention relates in particular to the use of an effective amount of at least one substance that modulates the expression and/or activity of LOX of sequence ID no. 1, and/or that modulates the expression and/or activity of NRAGE of sequence ID no. 2, for the manufacture of a composition for modulating the interaction between the LOX and NRAGE proteins in order to regulate the balance between the cellular phenomena of proliferation, differentiation and apoptosis, particularly in cases where the balance between these phenomena is disturbed, and especially in cases where the interaction between LOX and NRAGE is absent or altered. The invention makes it possible especially to treat and/or prevent skin ageing, lichen planus, graft-versus-host reaction (GVH), eczema, psoriasis and a cancer, particularly an epithelial cancer and more particularly a cutaneous epithelial cancer, of basocellular or spinocellular type.

1 - 29 . (canceled) 
     
     
         30 . A method of regulating the balance between cellular proliferation, differentiation and apoptosis in epithelial cells wherein a pharmaceutical or cosmetic composition is applied to an epidermis in need thereof, the composition comprising an effective amount of:
 i) at least one active ingredient which modulates the expression of the isoform of the human protein lysyl oxidase having the amino acid sequence of SEQ ID No. 1; or   ii) at least one active ingredient which modulates the expression of the human protein NRAGE having sequence ID No. 2; or   iii) a combination of the active ingredient of i) and the active ingredient of ii).   
     
     
         31 . The method according to  claim 30  wherein the epithelial cells are keratinocytes. 
     
     
         32 . The method according to  claim 31  wherein the active ingredient of i) increases by about 50% the expression of mRNA of lysyl oxidase in the keratinocytes. 
     
     
         33 . The method according to  claim 31  wherein the active ingredient of i) decreases by about 50% the expression of mRNA of lysyl oxidase in the keratinocytes. 
     
     
         34 . The method according to  claim 31  wherein the active ingredient of ii) increases by about 50% the expression of mRNA of NRAGE in the keratinocytes. 
     
     
         35 . The method according to  claim 31  wherein the active ingredient of ii) decreases by about 50% the expression of mRNA of NRAGE in the keratinocytes. 
     
     
         36 . A method of treating aging skin comprising topically administering onto the skin an effective amount of at least one substance which modulates the expression of LOX or NRAGE in the skin, said substance selected from the group consisting of a  Prunus spinosa  extract, an  Arbutus unedo  extract, a  Cassia amara  extract, a  Theobroma cacao  extract, a  Smilax ornate  extract, and a  Foeniculum  extract. 
     
     
         37 . The method of  claim 36  wherein the substance is an extract of  Smilax ornata.    
     
     
         38 . A method of treatment for disorders relating to epidermal hyperproliferation comprising administering an effective amount of a substance which stimulates the expression of NRAGE with sequence ID no. 2 to an epidermis in need thereof. 
     
     
         39 . The method of  claim 38  wherein the substance is an extract of  Ephedra sinica.    
     
     
         40 . The method of  claim 38  further comprising topically applying an effective amount of a second substance which inhibits the expression of LOX with sequence ID no. 1. 
     
     
         41 . The method of  claim 40  wherein the second substance is selected from the group consisting of a  Pterocarpus santalinus  extract, a  Gypsophila  spp. extract, and a  Bryonia dioica  extract. 
     
     
         42 . A method of treatment for disorders relating to epidermal hypoproliferation comprising topically applying an effective amount of a substance which stimulates the expression of LOX with sequence ID no. 1. 
     
     
         43 . The method according to  claim 42  wherein the substance is selected from the group consisting essentially of a soybean extract, an  Ephedra sinica  extract, a  Humulus lupulus  extract, a  Cinnamomum  spp. extract, a  Ruscus aculeatus  extract, a  Citrus limonia  extract, a  Citrus reticulate  extract, trans-3-hexanoate of ethyl, an  Amni visnaga  extract, alginic acid, a  Daucus carota  extract, methyl 2 methyl butyrate, an  Illicium verum  extract, a  Cupressus sempervirens  extract, an  asae foetida  gum, xylitol, a  Prunus spinosa  extract, an  Arbutus unedo  extract, a  Chimaphila umbellate  extract, an  Asperula odorata  extract, an  Artemisia vulgaris  extract, a  Sambucus nigra  extract, an extract of  Brassica Brassica campestris  var.  Pekinensis , a  Cassia amara  extract, a  Theobroma cacao  extract, a  Serica  extract, a  Smilax ornate  extract, a  Ribes rubrum  extract, an  Anacyclus pyrethrum  extract, a  Foeniculum  extract, or a combination thereof. 
     
     
         44 . The method according to  claim 42  further comprising topically applying an effective amount of a substance which inhibits the expression of NRAGE with sequence ID no. 2. 
     
     
         45 . A method for treating disorders relating to a high level of epidermal apoptosis comprising topically applying to the skin an effective amount of a substance which inhibits the expression of NRAGE with sequence ID no. 2. 
     
     
         46 . The method according to  claim 45  further comprising topically applying an effective amount of a substance which stimulates the expression of LOX with sequence ID no. 1. 
     
     
         47 . A cosmetic or pharmaceutical composition for modulating the interaction between LOX and NRAGE proteins in an epidermis, said composition comprising at least one substance selected from the group consisting of a soybean extract, an  Ephedra sinica  extract, a  Humulus lupulus  extract, a  Cinnamomum  spp. extract, a  Ruscus aculeatus  extract, a  Citrus limonia  extract, a  Citrus reticulate  extract, trans-3-hexenoate of ethyl, an  Amni visnaga  extract, alginic acid, a  Daucus carota  extract, methyl 2 methyl butyrate, an  Illicium verum  extract, a  Cupressus sempervirens  extract, an  asae foetida  gum, xylitol, a  Prunus spinosa  extract, an  Arbutus unedo  extract, a  Chimaphila umbellate  extract, an  Asperula odorata  extract, an  Artemisia vulgaris  extract, a  Sambucus nigra  extract, an extract of  Brassica Brassica campestris  var.  Pekinensis , a  Cassia amara  extract, a  Theobroma cacao  extract, a  Serica  extract, a  Smilax ornate  extract, a  Ribes rubrum  extract, an  Anacyclus pyrethrum  extract, a  Foeniculum  extract, a  Pterocarpus santalinus  extract, a  Gypsophila  spp. extract, and a  Bryonia dioica  extract; and at least one cosmetically or pharmaceutically acceptable excipient. 
     
     
         48 . The composition according to  claim 47  wherein the substance comprises between 0.01% volume/volume and 10% volume/volume of the composition. 
     
     
         49 . The composition according to  claim 47  wherein the substance is selected from the group consisting of a  Prunus spinosa  extract, an  Arbutus unedo  extract, a  Cassia amara  extract, a  Theobroma cacao  extract, a  Smilax ornate  extract, and a  Foeniculum  extract.