Mixture of purified sods of plant origin

Abstract

The present invention relates to an original and specific mixture of purified superoxide dismutases (SODs) of plant origin, characterised in that said mixture is essentially made up of three superoxide dismutases: a manganese superoxide dismutase, a copper and zinc superoxide dismutase and an iron superoxide dismutase provided in two isoforms, which can be obtained from an extract of the hybrid variety F1 of Cucumis melo MA 7950 or the cells thereof cultured in vitro or by transfer and expression of the genes of said SODs in prokaryotic or eukaryotic cells. The specific mixture according to the invention imparts to the compositions containing same a greater effectiveness in the treatment or prevention of diseases linked to inflammatory and / or oxidative stress, such as radiation-induced fibroses, cardiovascular diseases, obesity, atherosclerosis, labial herpes and myopathies, as well as in nutritional, pharmaceutical, veterinary or cosmetic uses.

Description

Blend of purified SODs of plant origin The present invention relates to a mixture of superoxide dismutases (SOD) extracted from Cucumis melo, in particular the Fl hybrid melon variety named MA 7950 or from its cells cultured in vitro or by transfer and expression of the genes of these SODs in prokaryotic or eukaryotic cells, its method of preparation, a cosmetic, nutritional, veterinary or pharmaceutical composition containing it as an active ingredient, as well as said composition for its use as a cosmetic care product, food supplement, beverage or medicine. Oxygen, essential for our bodily functions, nevertheless generates toxic reactive oxygen species that have a negative effect on our bodies. These reactive oxygen species are mostly free radicals such as the superoxide radical (O₂), the hydroxyl radical (OH⁻), nitric oxide (NO₂), or lipid-derived peroxide radicals (LO₂O⁻). The superoxide ion is the most abundant reactive oxygen species; it is directly formed from oxygen and is the precursor to all other reactive oxygen species, notably the highly aggressive hydroxyl radical (OH⁻). These free radicals are atoms or molecules whose electronic configuration is characterized by the presence of an unpaired electron. This characteristic makes them unstable and they can quickly oxidize other biological molecules such as nucleic acids (DNA), enzymatic proteins or membrane lipids, and particularly polyunsaturated fatty acids (PUFAs), in order to stabilize themselves. Our body constantly works against the formation of reactive oxygen species, which destroy cells. In every cell, there are constitutively several lines of defense to detoxify the cell. The first line of defense is provided by an enzyme called superoxide dismutase (SOD), which is a metalloenzyme (Mac Cord and Fridovich, J. Biol. Chem. 244: 6049-55, 1969). In the plant kingdom, there are three forms of SOD (Michalski, J. Chromatogr. B 684: 59-75, 1996), each characterized by the presence of a metal ion located at its active site: - one form of SOD contains copper and zinc (Cu / Zn-SOD), located mainly in the cytoplasm and chloroplast; - another form contains manganese (Mn-SOD), it is located in the mitochondria and peroxisome; - and finally, in some plant species a SOD contains iron (Fe-SOD), and is located in the chloroplast. SODs play a key role in combating free radicals by eliminating superoxide ions. Superoxide dismutases are enzymes capable of inducing the dismutation of superoxide ions, according to the following reaction: 2 ( + 2 H2O → O2 + H2O2 + 2 OH (equation 1). The action of SOD is complemented by a second line of defense which eliminates H2O2: catalase and / or selenium-dependent glutathione peroxidase (SeGPx), which ensure the destruction of hydrogen peroxide H2O2. Under normal biological conditions, the human body constantly produces small amounts of free radicals, which are immediately neutralized by existing defense systems. In certain cases, if free radical production increases (tobacco, stress, pollution, solar radiation, unbalanced diet, etc.), and / or if there is a deficiency in antioxidants, this leads to an oxidant / antioxidant imbalance. This imbalance induces significant cellular changes at the level of macromolecules (oxidation of DNA, proteins, sugars, and lipids) but also at the level of cellular organelles, particularly mitochondria, the cell's primary energy providers. When damaged, mitochondria become a major source of free radicals. This imbalance is increasingly correlated with numerous pathologies and imbalances.SOD, by neutralizing the superoxide anion, which is the origin of all reactive oxygen species and therefore of oxidative stress, plays a key role in the regulation of oxidative stress and the administration of exogenous SOD is being considered in the treatment of pathologies related to oxidative stress. Until now, the only purified SODs available were from the animal kingdom, notably extracted from bovine erythrocytes (Markovitz, J. Biol. Chem., 234, p. 40, 1959), from Escherichia Coli (Keele and Fridovitch, J. Biol, 245, p. 6176, 1970) and from marine bacterial strains (patents FR 2 225 443 and FR 2 240 277). Indeed, SOD, primarily the bovine Cu-Zn-SOD form, has been the subject of pharmaceutical development which led to a drug called Orgotein®. It has been used in pathologies induced by free radicals, particularly in the case of chronic inflammations such as in the treatment of Crohn's disease (Emerit et al, 1991, Free Rad. Res. Comms, 12-13, 563-569) or in the case of radiation-induced fibrosis (Delanian et al. 1994, Radiotherapy and Oncology, 32, 12-20). However, due in particular to the infectious substances that these materials may contain, these animal-derived SODs were, at least in France, quickly banned in the 1990s. As a result, the search for a source of SOD from the plant kingdom is the subject of constant interest in the field of pharmacy. Alternative compositions including plant-based SOD, particularly from melon, have therefore been proposed. The benefits derived from the use of melon-based food supplements are indeed well known, as illustrated by the article by Milind et al (International Research Journal of Pharmacy, 2011, 8, 52-57), the article by Voudoukis and Lacan et al (Journal of Ethnopharmacology 2004, 94, 67-75), or the article by Gene et al (Journal of Agricultural and Food Chemistry, 2008, 56, 3694-3698). Furthermore, melons generally have a particularly high SOD content compared to other fruits. The SOD extraction yield from melons is therefore high and economically viable. It should also be noted that extracts from other fruits, containing a sufficiently high SOD content to produce an effect, are not currently commercially available. Thus, formulations of SOD of plant origin, and in particular of melon, coated in a wheat gliadin matrix have also been described, for example in patent application FR 2 729 296 or for the product GLISODIN®, with the aim of protecting from gastric juices compositions including SOD intended for oral administration. Furthermore, patent FR 2 716 884 describes a protein extract of Cucumis melo, preferably variety 95LS444, exhibiting superoxide dismutase enzymatic activity exceeding 30 units / mg of soluble protein, its preparation process, and its use in pharmaceutical or cosmetic compositions for external topical application. However, such a protein extract, although rich in superoxide dismutase, cannot be used for many pharmaceutical applications, notably because it is neither sufficiently purified nor sufficiently active. Indeed, as indicated in Example 1, the protein extract of Cucumis melo variety 95LS444 exhibits a superoxide dismutase enzymatic activity of 126 U / mg of protein. Such an extract, derived from a Clipper melon (descendant of the Cucumis Melo variety 95LS444), is also described, with the same overall SOD content, in Lacan et al. (Planta 1998, 204, 377-382). It should be noted that this article describes a single isoform of Fe-SOD. There is therefore a need for a mixture of plant-based SOD with enhanced pharmaceutical activity to combat diseases related to oxidative stress and their consequences, particularly cardiovascular diseases and obesity and their consequences. Surprisingly, the applicant found a plant-based SOD mixture that possesses superior antioxidant properties compared to prior art SOD mixtures. In particular, the SOD mixture of the invention is more active than a SOD mixture derived from a protein extract of Cucumis Melo variety 95LS444 or one of its descendants, such as Clipper melon. Without being limited to this interpretation, it seems that the presence in said mixture of a particular isoform of iron superoxide dismutase, which has never been described to date, may confer on the mixture according to the invention its superior pharmaceutical properties. The present invention relates primarily to a mixture of plant-derived superoxide dismutases consisting essentially of three superoxide dismutases. The SOD mixture according to the invention possesses surprising properties and beneficial effects on the cardiovascular system, particularly on cardiac hypertrophy. Indeed, the SOD mixture according to the invention surprisingly modulates the expression of certain genes associated with heart disease and obesity, such as the NPPA or RXFP1 genes. The present invention also relates to a plant-derived iron SOD isoform (Fe-SOD) exhibiting particularly interesting antioxidant activity. The present invention also relates to a method for preparing said mixture of plant-derived superoxide dismutases consisting essentially of three superoxide dismutases. The present invention also relates to a method for preparing said plant-derived iron SOD isoform (Fe-SOD) exhibiting particularly interesting antioxidant activity. The present invention also relates to a nutritional, veterinary or pharmaceutical cosmetic composition containing as an active ingredient a mixture of purified superoxide dismutases according to the invention or the plant-derived iron SOD (Fe-SOD) isoform according to the invention, and at least one food-grade, pharmaceutically or cosmetically acceptable excipient. The present invention also relates to a composition according to the invention for its use as a medicinal product. The present invention therefore relates firstly to an original mixture of plant-derived superoxide dismutases consisting essentially of 3 superoxide dismutases: a manganese superoxide dismutase, a copper and zinc superoxide dismutase and an iron superoxide dismutase present in at least two isoforms, the first iron superoxide dismutase isoform with a molecular weight between 28,000 and 36,000 Da, the second iron superoxide dismutase isoform with a molecular weight between 75,000 and 85,000 Da, said mixture being capable of being obtained from an extract of the Fl hybrid variety of Cucumis Melo MA 7950 or from its cells cultured in vitro or by transfer and expression of the genes of these SODs in prokaryotic or eukaryotic cells, and said mixture preferably having a total SOD activity greater than or equal to 130 U / mg of the mixture. Preferably, said mixture can be obtained from an extract of the Fl hybrid variety of Cucumis Melo MA 7950 or from its in vitro cultured cells; more preferably, said mixture can be obtained from an extract of the Fl hybrid variety of Cucumis Melo MA 7950. It is noted incidentally that Cucumis Melo descended from the MA 7950 cell line or from one of the hybrid varieties derived from MA 7950 have a particularly high SOD content, both compared to other fruits and to other melon varieties. Thus, the SOD extraction yield from these specific Cucumis Melo is particularly high and economically viable. For the purposes of this invention, "consisting essentially of" means that the mixture comprises between 70 and 99.9%, advantageously between 80 and 99.9%, by weight, of superoxide dismutases.The other components of the mixture have minimal impact on its enzymatic activity. Preferably, the other components do not interfere with the enzymatic activity of superoxide dismutase. Preferably, the mixture according to the invention is extracted from the Fl hybrid variety of Cucumis Melo MA 7950, or from its cells cultured in vitro, or by transferring and expressing the genes of these SODs into prokaryotic or eukaryotic cells. Even more preferably, the mixture according to the invention is extracted from the Fl hybrid variety of Cucumis Melo MA 7950, or from its cells cultured in vitro. It should be noted that a person skilled in the art, using their general knowledge, can obtain the peptide sequence of the SODs in the mixture according to the invention, and then, using well-known techniques, can generate the corresponding mRNA (messenger RNA) and cDNA (complementary DNA). The latter can then be transferred, using well-known techniques, into prokaryotic or eukaryotic cells, which will subsequently be used to produce the SOD mixture according to the invention. The "Cucumis Melo MA 7950 cells cultured in vitro" include, within the meaning of the present invention, both cells directly from the plant and cultured in vitro according to techniques well known to those skilled in the art, and in particular stem cells, and cells derived from these first cells. The hybrid variety Fl of Cucumis melo MA 7950, whose seeds were deposited in accordance with the Budapest Treaty in the NCIMB collection (National Collection of Industrial and Marine Bacteria-ABERDEEN AB2 IRY (Scotland - GB) 23 St. Machar Drive) on July 8, 2013, under number NCIMB 42154, possesses unique characteristics regarding its appearance, stress resistance, and SOD composition. This SOD mixture has superior antioxidant properties compared to other SOD mixtures from other plant sources, particularly those from other melon varieties. For the purposes of this invention, "extract" means a protein extract, preferably a soluble protein extract. For the purposes of this invention, "SOD" refers to a superoxide dismutase enzyme. It should be noted that the superoxide dismutases according to this invention are natural, meaning they are not chemically modified. In particular, this invention relates to whole SODs, and not to fragments thereof. SODs are classified into three categories, based on the metal present in their active site: manganese superoxide dismutases (Mn-SOD), copper and zinc superoxide dismutases (Cu / Zn-SOD), and iron superoxide dismutases (Fe-SOD). The mixture according to the present invention contains at least two Fe-SOD isoforms. Isoforms of a protein are the different forms it takes when derived from different genes, or from the same gene by alternative splicing. In what follows, these two Fe-SOD isoforms will be referred to as the "first isoform" and the "second isoform" based on their molecular weight. Thus, the "first isoform" according to the invention has a lower molecular weight than the "second isoform." It should be noted that other SODs (Mn-SOD and / or Cu / Zn-SOD) may also be present in the mixture in several isoforms. Thus, according to the present invention, the term Mn-SOD (respectively Cu / Zn-SOD) covers all the isoforms of Mn-SOD (respectively Cu / Zn-SOD) present in the mixture. SODs catalyze the disproportionation of superoxide ions according to the reaction: 2 O2' + 2 H2O → O2 + H2O2 + 2 OH (equation 1).The mixture according to the invention is characterized by its total SOD activity. "Total SOD activity" is understood, for the purposes of this invention, to mean the quantification of the disproportionation reaction described in equation 1 by the mixture according to the invention. This total SOD activity is measured using techniques well known to those skilled in the art and is expressed in U (enzyme units) per mg of protein. Preferably, it is measured using a method based on the reduction of the tetrazolium salt. In particular, the method of Beauchamp and Fridovich (Anal. Biochem. 44:276-82 (1971)), based on the inhibition of the reduction of Nitroblue Tetrazolium (N 55 14 Sigma-Aldrich, France) by SOD, and modified by Oberley and Spitz in 1985 (Boca Raton CRC Press; in R.A. Grenwald 1985, ed.: Handbook of Methods for Oxygen Radical Research, pp. 217-230), may be cited.The SOD assay kit (19160, Sigma-Aldrich, France), also based on the reduction of tetrazolium salt, can also be used. This kit is a variant of the previous method but easier to implement. The SOD mixture according to the invention preferably exhibits a total SOD activity greater than 130 U / mg of said mixture, even more preferably greater than 300 U / mg of said mixture, and most preferably greater than 500 U / mg of said mixture. Furthermore, it is also possible to determine the SOD activity attributed to each SOD (Mn-SOD, Cu / Zn-SOD, and Fe-SOD). This "relative" SOD activity quantifies the contribution of each SOD (or one of its isoforms) to the total SOD activity of the mixture. It is thus expressed as a percentage of the total SOD activity of the mixture. The SOD activity of each SOD (or one of its isoforms) is measured using techniques well known to those skilled in the art. Indeed, the different forms of SOD can be identified using different inhibitors: KCN inhibits the activity of Cu / Zn SOD; H₂O₂ inhibits the activity of Fe SOD and Cu / Zn SOD, while Mn SOD is insensitive to H₂O₂ and KCN (Paul and Van Alstyne, J Exp. Mar. Biol Ecol. 160: 191-203 1992). Thus, the total SOD activity of the mixture is measured first. The method for determining the different forms of SOD, well known to those skilled in the art, consists of separation by acrylamide gel electrophoresis under native conditions, followed by detection of SOD activity on the gel. Samples of the SOD mixture according to the invention are deposited in the different wells of an electrophoresis gel. Migration under non-denaturing conditions is then performed. During the gel development step, the gel is divided into three parts. The first part is developed for total SOD activity, the second is pre-incubated with 2 mM KCN ​​and then developed for SOD activity under the same conditions, and the last part is pre-incubated with 5 mM H₂O₂ and then developed for SOD activity under the same conditions. The intensities of the different bands are measured by integrating the air under the curve, and their ratio indicates the relative SOD activities of the different SODs (or their isoforms) in the mixture according to the invention. An example of determining the relative SOD activity of the different SODs in the mixture is illustrated in the examples. Thus, the mixture of superoxide dismutases according to the invention is advantageously such that the cumulative SOD activity of the two iron superoxide dismutase isoforms is between 20% and 26%, advantageously between 22% and 26% of the total SOD activity of the mixture. According to a preferred embodiment of the invention, the mixture of purified superoxide dismutases is such that the cumulative SOD activity of the two iron superoxide dismutase isoforms is between 20% and 26%, advantageously equal to 25%, of the total SOD activity of the mixture, the activity of copper and zinc superoxide dismutase is between 60% and 70%, advantageously equal to 65%, of the total SOD activity of the mixture, and the activity of manganese superoxide dismutase is between 9% and 15%, advantageously between 7% and 12%, even more advantageously equal to 10% of the total SOD activity of the mixture. SODs, like all proteins, can be separated based on two biochemical characteristics: their molecular mass and their isoelectric point. The separation of the different forms of SOD can be carried out by acrylamide gel electrophoresis under native conditions, followed by detection of SOD activity on the gel. Visualization of the different SODs and measurement of SOD activity are performed using the method of Beauchamp and Fridovich (Anal. Biochem. 44:276-82, 1971). The molecular weights of the different forms of SOD can be determined using molecular weight markers (proteins of known molecular weight) to calibrate the electrophoresis gel. The different forms of SOD are revealed as described above, and the positions of the resulting bands are compared to those of the molecular weight markers to determine the molecular weights of each SOD isoform. Thus, preferably, the mixture according to the invention comprises an iron superoxide dismutase present in at least two isoforms, the first with a molecular weight between 28,000 and 36,000 Da, the second with a molecular weight between 75,000 and 85,000 Da. Advantageously, the first iron superoxide dismutase isoform of the SOD mixture according to the invention has a molecular weight of about 32,200 Da. Advantageously, the second iron superoxide dismutase isoform of the SOD mixture according to the invention has a molecular weight of approximately 79,800 Da. In a preferred embodiment, manganese superoxide dismutase has a molecular weight between 70,000 and 90,000 Da, and copper and zinc superoxide dismutase has a molecular weight between 27,000 and 35,000 Da. According to a preferred variant of the invention, Cu / Zn-SOD has a molecular weight between 27,000 and 35,000 Da, advantageously 31,800 Da, and Mn-SOD has a molecular weight between 70,000 and 90,000 Da, advantageously 80,600 Da. For Fe-SOD, the first isoform has a molecular weight between 28,000 and 36,000 Da, advantageously equal to 32,200 Da, the second Fe-SOD isoform has a molecular weight between 75,000 and 85,000 Da, advantageously equal to 79,800 Da. The separation of SODs according to their charge is achieved by isoelectric focusing (IEF). SODs migrate in an electric field and become immobilized when the surrounding pH makes their overall charge zero. The isoelectric points (or pI) of the different SOD forms can be determined on IEF gels by comparison with known isoelectric point markers (IEF markers 3.6-9.3, Reference 56733, Sigma-Aldrich, France). By isoelectric point or pHi, we mean in the context of the present invention the pH for which the overall charge of this molecule is zero or, in other words, the pH for which the molecule is electrically neutral. Preferably, Cu / Zn-SOD has a pHi of 4.3. Advantageously, the two isoforms (the first and the second) of Fe-SOD have a pHi of 4.4 and 4.7 respectively. According to a preferred embodiment of the invention, Cu / Zn-SOD has a pHi of 4.3, Fe-SOD has a pHi of 4.4 and 4.7 and the different isoforms of Mn SOD have pHi of 4.1; 4.4; 5.3; 5.5; 5.7; 5.85; 6.1. Furthermore, the present invention relates to a method for preparing the superoxide dismutase mixture according to the invention. This method comprises the successive steps of: - grinding or pressing in aqueous medium, preferably at pH 5 to 9, of the Fl hybrid variety of Cucumis Melo MA 7950 or of its cells cultured in vitro or by transfer and expression of the genes of these SODs in prokaryotic or eukaryotic cells, - recovery of the supernatant, and - purification by chromatography, in particular by IMAC chromatography. Thus, the mixture of superoxide dismutases according to the invention, preferably purified, can be obtained by the process comprising the successive steps of: - grinding or pressing in aqueous medium, preferably at pH 5 to 9, of the Fl hybrid variety of Cucumis Melo MA 7950 or of its cells cultured in vitro or by transfer and expression of the genes of these SODs in prokaryotic or eukaryotic cells, - recovery of the supernatant, and - purification by chromatography, in particular by IMAC chromatography (“Immobilized metal ion affmity chromatography”). Immobilized metal ion affinity chromatography (IMAC) is based on the affinity of certain amino acids, particularly histidine, tryptophan, and cysteine, for metals. This chromatographic technique works by allowing proteins with an affinity for metal ions to be retained on a column containing immobilized metal ions, such as cobalt, nickel, and copper. The eluents used generally exhibit a pH gradient or a concentration gradient of a competitive molecule that binds to the ions in the column, such as imidazole. Preferably, IMAC chromatography is performed using a column containing copper ions as the immobilized metal ions.Thus, the elution rate of proteins depends on their charge and their affinity for the metal ion, particularly copper, and is therefore correlated with the presence of amino acids such as tryptophan, histidine, and cysteine ​​in the protein sequence. Advantageously, a gradient of aqueous solutions of NH4Cl and CuSO4 will be used as the eluent. Alternatively, the process according to the invention comprises the successive steps of: - grinding or pressing in aqueous medium, preferably at pH 5 to 9, of the Fl hybrid variety of Cucumis Melo MA 7950 or of its cells cultured in vitro or by transfer and expression of the genes of these SODs in prokaryotic or eukaryotic cells, - recovery of the supernatant, and - successive membrane purifications, in particular by passing the supernatant through membranes with variable porosity. A person skilled in the art will be able to adapt the membrane porosity gradient in the process according to the ripeness and dry matter content of the melon, particularly by seeking to avoid membrane clogging. As mentioned above, it appears that the presence of the second iron isoform of superoxide dismutase, which has never been described to date, could confer superior biological properties to the mixture according to the invention. This second isoform of iron superoxide dismutase that can be obtained from an extract of the Fl hybrid variety of Cucumis Melo MA 7950 has a molecular weight between 75,000 and 85,000 Da. Thus, more generally, the present invention relates to a superoxide dismutase SODi (synthetic or natural) whose polypeptide sequence is homologous to the sequence of the second isoform, and in particular has a sequence identity greater than or equal to 80%, preferably 85%, 90%, 95% or 98%, with the sequence of the second isoform. A homologous polypeptide sequence of the second isoform includes any polypeptide sequence that differs from the sequence of the second isoform by mutation, insertion, deletion or substitution of one or more amino acids, provided that it exhibits the biological activity of the second isoform. By "percentage of identity" between two amino acid sequences within the meaning of the present invention, we mean a percentage of identical amino acid residues between the two sequences to be compared, obtained after the best alignment (optimal alignment), this percentage being purely statistical and the differences between the two sequences being randomly distributed over their entire length. Sequence comparisons between two amino acid sequences are traditionally performed by comparing these sequences after having aligned them optimally, said comparison being performed segment by segment or by "comparison window". The optimal alignment of the sequences for comparison can be performed, in addition to manually, by means of the local homology algorithm of Smith and Waterman (1981) [Ad. App. Math. 2:482], by means of the local homology algorithm of Neddleman and Wunsch (1970) [J. Mol. Biol.48:443], using the Pearson and Lipman (1988) similarity search method [Proc. Natl. Acad. Sci. USA 85:2444], using computer software employing these algorithms (GAP, BESTFIT, FASTA and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI, or using BLAST N or BLAST P comparison software). The percentage of identity between two amino acid sequences is determined by comparing these two optimally aligned sequences. In this alignment, the amino acid sequence being compared may include additions or deletions relative to the reference sequence. The percentage of identity is calculated by determining the number of identical positions where the amino acid residue is the same in both sequences, dividing this number of identical positions by the total number of positions in the comparison window, and multiplying the result by 100 to obtain the percentage of identity between the two sequences. For example, one can use the BLAST program, "BLAST 2 sequences" (Tatusova et al., "Blast 2 sequences - a new tool for comparing protein and nucleotide sequences", FEMS Microbiol, 1999 Lett. 174:247-250) available on the website http: / / www.ncbi.nlm.nih.gov / gorf / bl2.html, the parameters used being those given by default (in particular for the parameters "open gap penalty": 5, and "extension gap penalty": 2; the matrix chosen being for example the "BLOSUM 62" matrix proposed by the program), the percentage of identity between the two sequences to be compared being calculated directly by the program. For the purposes of this invention, "amino acid" means all residues of natural α-amino acids (e.g., Alanine (Ala), Arginine (Arg), Asparagine (Asn), Aspartic acid (Asp), Cysteine ​​(Cys), Glutamine (Gin), Glutamic acid (Glu), Glycine (Gly), Histidine (His), Isoleucine (Ile), Leucine (Leu), Lysine (Lys), Methionine (Met), Phenylalanine (Phe), Proline (Pro), Serine (Ser), Threonine (Thr), Tryptophan (Trp), Tyrosine (Tyr), and Valine (Val)) in the D or L form, as well as non-natural amino acids (e.g., β-alanine, allylglycine, tert-leucine, 3-aminoadipic acid, 2-aminobenzoic acid, 3-Aminobenzoic acid, acid 4-aminobenzoic acid, 2-aminobutanoic acid, 4-amino-l-carboxymethyl piperidine, 1-amino-l-cyclobutanecarboxylic acid, 4-aminocyclohexaneacetic acid, 1-amino-l-cyclohexanecarboxylic acid, (1R,2R)-2-aminocyclohexanecarboxylic acid, (1R,2S)-2-aminocyclohexanecarboxylic acid, (1S,2R)-2-aminocyclohexanecarboxylic acid, (1S,2S)-2-aminocyclohexanecarboxylic acid, 3-aminocyclohexanecarboxylic acid, 4-aminocyclohexanecarboxylic acid, (1R,2R)-2-aminocyclopentanecarboxylic acid, (1R,2S)-2-aminocyclopentanecarboxylic acid 1-amino-l-cyclopentanecarboxylic acid, 1-amino-l-cyclopropanecarboxylic acid, 4-(2-aminoethoxy)benzoic acid, 3-aminomethylbenzoic acid, 4-aminomethylbenzoic acid, 2-aminobutanoic acid, 4-aminobutanoic acid, 6-aminohexanoic acid, 1-aminoindane-l-carboxylic acid, 4-aminomethylphenylacetic acid, 4-aminophenylacetic acid, 3-amino-2-naphthoic acid,4-Aminophenylbutanoic acid, 4-Amino-5-(3-Indolyl)pentanoic acid, (4R,5S)-4-Amino-5-Methylheptanoic acid, (R)-4-Amino-5-Methylhexanoic acid, (R)-4-Amino-6-Methylthiohexanoic acid, (S)-4-Aminopentanoic acid, (R)-4-Amino-, 5-phenylpentanoic acid, 4-aminophenylpropionic acid, (R)-4-aminopimeric acid, (4R,5R)-4-amino-5-hydroxyhexanoic acid, (R)-4-amino-5-hydroxypentanoic acid, (R)-4-amino-5-(p-hydroxyphenyl)pentanoic acid, 8-aminooctanoic acid, (2S,4R)-4-aminopyrrolidine-2-carboxylic acid, (2S,4S)-4-aminopyrrolidine-2-carboxylic acid, azetidine-2-carboxylic acid, (2S,4R)-4-benzylpyrrolidine-2-carboxylic acid, (S)-4,8-diaminooctanoic acid, tert-butylglycine, γ-carboxyglutamate, the β-Cyclohexylalanine, citrulline, 2,3-Diaminopropionic acid, hippuric acid, rhomocyclohexylalanine, moleucine, homophenylalanine, 4-Hydroxyproline, indoline-2-carboxylic acid, isonipecotic acid, α-Methylalanine, nicopetic acid, norleucine, norvaline, octahydroindole-2-carboxylic acid, ornithine, penicillamine, phenylglycine, 4-Phenylpyrrolidine-2-carboxylic acid, pipecolic acid,propargylglycine, 3-pyridinylalanine, 4-pyridinylalanine, l-pyrrolidine-3-carboxylic acid, sarcosine, statins, tetrahydroisoquinoline-l-carboxylic acid, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, tranexamic acid). The term also includes natural and non-natural amino acids bearing a conventional amino-protecting group (e.g., an acetyl, tert-butyloxycarbonyl, benzyloxycarbonyl, or 9-fluorenylmethylcarbonyl group), as well as natural and non-natural amino acids protected at the carboxyl end (advantageously by an alkyl group in (Cl-Cl8), an ester, a phenyl or benzyl amide, or an amide, which respectively give carboxyl ends of the following formulas: -CO(alkyl Cl-Cl8), -COO(alkyl Cl-Cl8), -CONHphenyl CONHbenzyl, or CONH2). For amino acid sequences exhibiting at least 80%, preferably 85%, 90%, 95%, and 98% identity with a reference amino acid sequence, preference is given to those exhibiting certain modifications compared to the reference sequence, in particular a deletion, addition, or substitution of at least one amino acid, truncation, or elongation. In the case of a substitution of one or more consecutive (or non-consecutive) amino acids, preference is given to substitutions in which the substituted amino acids are replaced by "equivalent" amino acids. The term "equivalent amino acids" here refers to any amino acid that can be substituted for one of the amino acids in the basic structure without, however, substantially altering the biological activities of the corresponding antibodies, as defined subsequently, particularly in the examples. These equivalent amino acids can be determined based, for example, on their structural homology with the amino acids they replace. This search for similarities in a polypeptide sequence takes into account conservative substitutions which are substitutions of amino acids of the same class, such as substitutions of amino acids with uncharged side chains (such as asparagine, glutamine, serine, threonine, and tyrosine), of amino acids with basic side chains (such as lysine, arginine, and histidine), of amino acids with acidic side chains (such as aspartic acid and glutamic acid); of amino acids with polar side chains (such as glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan, and cysteine). Preferably, "variant", "homologous", or "derived" superoxide dismutases are of the same length as the reference sequences.Thus, advantageously, the superoxide dismutase sequence according to the SODi invention consists of the sequence of the second iron isoform of superoxide dismutase that can be obtained from an extract of the Fl hybrid variety of Cucumis Melo MA 7950 with a molecular weight between 75,000 and 85,000 Da. Most advantageously, the present invention relates to the second isoform of iron superoxide dismutase obtainable from an extract of the hybrid variety Fl of Cucumis Melo MA 7950 with a molecular weight between 75,000 and 85,000 Da. This can be obtained by a process comprising the successive steps of: - grinding or pressing in aqueous medium at pH of 5 to 9 of the hybrid variety Fl of Cucumis Melo MA 7950 or its cells cultured in vitro or by transfer and expression of the genes of these SODs in prokaryotic or eukaryotic cells, - recovery of the supernatant, and - purification by chromatography, in particular by IMAC chromatography. The present invention also relates to any mixture comprising said superoxide dismutase SODi. The present invention also relates to a cosmetic, nutritional, veterinary or pharmaceutical composition containing as an active ingredient superoxide dismutase SODi or the mixture of superoxide dismutases according to the invention, and at least one food-grade or pharmaceutically or cosmetically acceptable excipient. For the purposes of the present invention, the term "pharmaceutical composition" covers both a composition for pharmaceutical or veterinary use, that is to say, it is intended to be used to treat an animal, including a human. For the purposes of this invention, "animal" means, for example, a mammal, a fish, a crustacean, a reptile, or a bird. In particular, mammals include humans. For the purposes of this invention, the term "nutritional composition" includes, in particular, nutraceutical compositions (especially food supplements, for example, in solid or liquid form), dietary compositions, and beverages, particularly those with dietary or nutritional properties, such as antioxidant beverages. Preferably, a nutritional composition comprises nutraceutical compositions and dietary beverages, such as antioxidant beverages. In this description, a food, pharmaceutical, or cosmetically acceptable excipient is defined as a compound or combination of compounds used in a nutritional, pharmaceutical, or cosmetic formulation that does not cause adverse reactions and that, for example, facilitates the administration of the active compound(s), increases its lifespan and / or effectiveness in the body, increases its solubility in solution, or improves its preservation. These acceptable excipients are well-known and will be adapted by a person skilled in the art according to the nature and route of administration of the chosen active compound(s). Advantageously, the nutritional, cosmetic or pharmaceutical composition according to the invention has a superoxide dismutase content of between 0.01 and 10% by weight, for example between 0.01 and 5% by weight of superoxide dismutase(s), or between 0.01 and 1% by weight, relative to the total weight of the composition. In one embodiment, the cosmetic composition according to the invention is intended for external topical use such as skincare products, shampoos, lotions, gels. When the composition according to the invention is intended for nutritional use, it is advantageously intended for oral administration. For example, the nutritional composition according to the invention is in the form of a tablet, capsule, soft gel capsule, effervescent tablet, sachet or stick to be dissolved, chewing gum, beverage, juice, yogurt, confectionery, biscuit or bars. When the composition according to the invention is intended for pharmaceutical use, it is intended for administration by topical, oral, nasal, or parenteral routes. For example, the pharmaceutical composition according to the invention is in the form of a tablet, capsule, soft gel, effervescent tablet, sachet or stick for dilution, syrup, elixir, herbal tea, chewing gum, spray, aerosol, or injectable solution. In a preferred embodiment, the pharmaceutical composition according to the invention is intended for oral administration. For oral administration, the composition according to the invention can be effectively protected from gastric juices by coatings well known to those skilled in the art, in particular vegetable fats (see French patent FR 2 822 381) or modified starch particles (see international application WO2006 / 030111). Thus, the compositions according to the invention can be delivered effectively orally and induce an increase in the synthesis of endogenous superoxide dismutase and glutathione peroxidase in each organ where oxidative stress is present, which allows for an effective and constant fight against pathologies related to oxidative stress. In a particular embodiment, the pharmaceutical, cosmetic, veterinary or nutritional composition according to the invention contains another active ingredient, advantageously another antioxidant. The present invention also relates to a composition according to the invention for its use as a medicinal product. Administration of SODi or the SOD mixture according to the invention induces the endogenous synthesis, by the cell, of SOD and a second-line defense enzyme: glutathione peroxidase. This allows the cell and the body to effectively and sustainably combat oxidative stress. Thus, the drug is primarily intended to treat or prevent diseases related to oxidative stress and / or inflammation and / or to enhance the action of other antioxidants used in animals. The drug may also be intended to stimulate cell vitality in animals. In one embodiment, the composition according to the invention, for use as a medicinal product, is administered in combination with another medicinal product. Preferably, this medicinal product is also intended to treat or prevent diseases related to oxidative stress and / or inflammation and / or to enhance the action of other pharmaceutical molecules, and in particular other antioxidants used in animals. This medicinal product may also be intended to treat orphan diseases. In one embodiment of the invention, the animal is chosen from the group of livestock, companion or laboratory animals, advantageously chosen from the group consisting of pigs, cattle, horses, sheep, goats, deer, poultry, rabbits, aquaculture animals, fish, crustaceans, advantageously shrimp and crabs, reptiles, advantageously turtles and crocodiles, birds, felines, rodents, advantageously mice, rats and guinea pigs, and canids, advantageously from among ruminants and monogastrics. In such animals, the disease linked to oxidative stress and / or inflammation is preferably chosen from among chronic inflammations such as osteoarthritis, tendonitis, laminitis, autoimmune diseases, mastitis resulting in the presence of cells in the milk, embryonic mortality during animal reproduction, the effects of stress caused by a change in temperature, diet, stocking density, habitat, during competitions, intense and / or prolonged exercise, such as work, walking or running, vaccinations, intensive feeding or during transition periods such as farrowing, laying, weaning, change of pool, start-up in rearing, for example, placement in a nursery, brooder or fry rearing, lactation, transport, grouping, reproductive disorders of animals, for example, poor maturation of follicles and / or ova,Specific and non-specific immune disorders in animals, including microbial, viral, and parasitic infections, and / or a lack of resistance in their bodies to disease, and oxidative stress. In another embodiment of the invention, the animal is man. In this case, diseases related to oxidative stress and / or inflammation are advantageously chosen from the group consisting of allergies, for example eczema, vitiligo, lupus, disorders related to exposure to UV radiation, post-irradiation dysfunctions, in particular fibroses of various origins and cystitis, infertility, respiratory pathologies, in particular asthma, anemia, rheumatoid arthritis and osteoarthritis, in particular osteoarthritis of the knee or finger, genitourinary disorders, in particular Peyronie's disease, problems related to ischemia-reperfusion, pathologies of the nervous system, in particular hypoxia, cardiovascular diseases, in particular hypertension, obesity, type II diabetes, cancer treatment, in particular colorectal cancers or melanomas, colorectal inflammations,These include Crohn's disease, neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS), ulcerative colitis, vision disorders such as age-related macular degeneration (AMD), mitochondrial dysfunction, degenerations caused by infectious agents such as AIDS and hepatitis C, and degenerations linked to drug use or exposure to toxic chemicals such as pesticides. Other examples include rare diseases such as cystic fibrosis, Friedreich's ataxia, and alopecia. Furthermore, it can be used to improve fertility and the viability of stem cells, allowing for better use and effectiveness in cell therapies, particularly for inflammatory joint diseases, bone marrow diseases, and neurodegenerative diseases such as Alzheimer's. Finally, the mixture according to the present invention, due to its particularly advantageous antioxidant action, is also useful in the treatment of myopathies (for a reference linking myopathy and oxidative stress, see Functional muscle impairement in fascioscapulo humerai muscular distrophy is correlated with oxidative stress and mitochondrial dysfunction. Turki et al, 2012. Free Radical Biology and Medicine: 1:53(5) 1068-1079). Furthermore, as stated above, the SOD mixture according to the invention beneficially modulates the expression of NPPA and RXFPl genes in animals, particularly in humans. The NPPA gene codes for a protein belonging to the natriuretic peptide family, which is involved in extracellular fluid volume and electrolyte homeostasis. The human NPPA gene codes for a 151-amino-acid (AA) preprohormone. After cleavage of the 25-AA N-terminal signal sequence, the resulting prohormone (proANP) is 126 AA and is stored in atrial secretory granules. When secreted, proANP is converted into active ANP (Atrial Natriuretic Peptide) (1). ANP secretion is essentially dependent on a mechanical stimulus; changes in blood volume regulate GANP via variations in atrial wall tension, thus promoting a decrease in blood pressure. ANP therefore has an anti-hypertrophic effect. In cases of hypertrophy or heart failure, pro-ANP and GANP are secreted into the ventricular myocardium, leading to their increase in plasma levels in cases of heart disease (1). ANP plays a role in regulating cardiac electrophysiology by acting on the autonomic nervous system, inhibiting sympathetic activity, activating parasympathetic activity, and specifically regulating cardiac ion channels (2). The NPPA gene constitutes a therapeutic target for selectively regulating the progression of cardiovascular diseases (1), as it is stimulated in cases of cardiac pathology (3).Diseases associated with the NPPA gene include acute myocardial infarction, mitral valve disease, heart failure, hypertension, fluid overload, and cardiac hypertrophy. Mutations in this gene are associated with atrial fibrillation (2). High NPPA expression in the heart is implicated in the pathophysiology of hypertension and heart failure (3). The RXFP1 receptor, also known as LGR7 (Leucine-rich-repeat containing G-protein-coupled Receptor 7), is a 757-amino-acid polypeptide belonging to the insulin superfamily. It is a transmembrane receptor that binds relaxin with high affinity. It is coupled to a G protein and has seven transmembrane domains. Furthermore, its ectodomain contains ten leucine-rich repeats (LRRs) and is composed of class A lipoproteins: LDL (low-density lipoprotein α) at ​​the terminal amino point. This influences receptor maturation, cell surface positioning, and relaxin signaling. This receptor is therefore fundamental to cell signaling and signal transduction. Relaxin receptors are found in reproductive tissues, the brain, kidneys, heart, and lungs where the action of relaxin has been established (4).At the cardiac level, RXFP1 receptors are primarily located in the atrium, rather than the ventricle. However, it is established that RXFP1 mRNA expression also occurs in the ventricle of rats, mice, and humans. The high density of RXFP1 in the atrium is linked to the inotropic and chronotropic response of relaxin. Following the activation of RXFP1 receptors and signal transduction, relaxin has various effects. Relaxin's function is not limited to the reproductive system; this peptide affects cardiac function and participates, among other things, in the regulation of blood pressure, blood flow, and fluid balance (5). Relaxin has antifibrotic, antihypertrophic, anti-inflammatory, and vasodilatory effects. It also reduces blood pressure and increases cardiac output, and it can also stimulate myocardial regeneration (4, 5). mR A RXFP1 levels are decreased in the left atrium and ventricle in the MI (myocard Infact) rat (4). Thus, the SOD mixture according to the present invention is advantageously used for the treatment of cardiovascular diseases, in particular acute myocardial infarction, mitral valve disease, heart failure, hypertension, fluid overload, cardiac hypertrophy, hypertension and heart failure, particularly in humans. The SOD mixture according to the present invention is also advantageously used for the treatment of obesity and arteriosclerosis. Furthermore, it has been found that the SOD mixture according to the present invention is useful for the treatment of herpes, particularly cold sores, especially in men. The present invention also relates to a composition according to the invention for use as a nutritional, food, or cosmetic composition. In this case, the composition aims to combat the effects of daily oxidative stress, such as fatigue, stress, anxiety, joint problems, athletic recovery, male or female fertility problems, erectile dysfunction, vision problems, wound healing, cellulite, UV damage, and acne. FIGURES Figure 1: Determination of the different SODs from the Fl MA 7950 hybrid melon (schematic representation of the result obtained after detection on acrylamide gel). Total SOD activity (well 1), with 2mM KCN ​​(well 2), with H2O2 (well 3). Figure 2: Electrophoretic profile of the different SODs from the Fl MA 7950 hybrid melon (schematic representation of the result obtained after development on IEF gel), from left to right, of the MA 7950 melon (wells 1 and 2), of watermelon (wells 3 and 4), of peach (wells 5 and 6) and of nectarine (wells 7 and 8). Figure 3: Electrophoretic profile of the different SODs from the Fl MA 7950 hybrid melon (schematic representation of the result obtained after development on an IEF gel), from left to right: MA 7950 melon (wells 1 and 2), Canary melon (wells 3 and 4), apricot (wells 5 and 6), and cherry (wells 7 and 8). Figure 4: Photograph of two melons, just after harvesting (t0). On the left is a common Fl hybrid melon; on the right is a melon from the Fl hybrid melon variety named MA 7950. Figure 5: Photograph of the same two melons taken 7 days later. On the left is the common Fl hybrid melon, on the right is the melon from the Fl hybrid melon variety named MA 7950. EXAMPLES The following examples are presented for illustrative purposes only and do not constitute a limitation of the invention in any way. Example 1. Specificity of the hybrid melon variety Fl named MA 7950 A simple experiment was implemented to demonstrate the particular properties of melons from the Fl hybrid melon variety named MA 7950, and in particular its antioxidant activity. Two melons, one of the common type and the other of the Fl hybrid melon variety MA 7950, were placed in a room at room temperature and atmospheric pressure on day J1 (Figure 4). The melons were kept in this room under the same conditions (room temperature, atmospheric pressure) for 7 days (Figure 5, photograph of the same melons taken on day J8). After 7 days, the common Fl hybrid melon was clearly in an advanced state of degradation, while the Fl hybrid melon variety MA 7950 still had a good external appearance. The twice-as-high SOD content and composition of the mixture in the Fl hybrid melon variety MA 7950 allowed the melon cells to resist the natural degradation process more effectively. Example 2. Preparation of the extract and purification of the different SODs, determination of SOD activity 5 g of pulp from a Cucumis melo hybrid variety Fl named MA 7950, or of its cells, are ground in a cold mortar. A 50 mM phosphate buffer (pH 7.8; 1 mM EDTA; 5% glycerol) equivalent to three times the plant mass is added. After homogenization, the suspension is centrifuged at 5000 g at 4°C for 30 minutes. The supernatant is then collected and filtered. This crude extract is used to purify the different forms of SOD. The various SODs were purified using a technique well-known to those skilled in the art: immobilized metal chromatography (IMAC). In this method, copper is used as the metal ion immobilized on the column; protein binding is charge-dependent and therefore correlated with the presence of amino acids such as tryptophan, histidine, and cysteine. SODs are known for their high histidine content, therefore the use of IMAC is justified. SODs from the MA 7950 melon extract were purified on a FPLC (Pharmacia Amersham) using a Superose HR 10 / 2 column or a Hitrap chelating column (pharmacia-Biotech). Three ml of sample were injected via a superloop onto the column, which had been pre-treated with a CuSO4 solution (600 ml, 23 mmol / ml) and equilibrated with 10 ml of 0.05 M potassium phosphate buffer, pH 7.8. The elution of the SODs is carried out at a constant flow rate of 1 ml / min by a linear gradient of 10% (reached in 10 min) of a 0.75 M NH4Cl solution. The remaining Cu-protein complexes are removed by 5 ml of an aqueous 1 M EDTA solution. 2 ml fractions containing the different SODs are collected, quantified and immediately desalinated on an Amicon PM 10 cell with 4 volumes of 0.05 M phosphate buffer pH 7.8, then lyophilized. Example 3. Determination of the different forms of SOD and molecular weights: SOD activity is revealed on acrylamide gels under native conditions (conditions in which the protein remains in its native state, i.e., as is and within the cell, as opposed to denaturing conditions in which the protein is linearized) according to the method of Beauchamp and Fridovich, Anal. Biochem. 44: 276-82 (1971). This method is based on the inhibition of the reduction of Nitroblue Tetrazolium (N 55 14 Sigma-Aldrich, France) by SOD. After detection, the different bands corresponding to SOD activity appear white against a dark blue gel background. Samples of the purified SOD mixture (45 μA of solution A + 15 μA of migration buffer) are loaded into the different wells of an electrophoresis gel (4% / 10% acrylamide). The migration takes place over 75 minutes at 70mA and 300V. During the development stage of the gel which migrated under non-denaturing conditions, the gel is cut into 3 parts.The first is revealed to be active according to the protocol below, the second is pre-incubated with 2 mM of KCN and then revealed to be active, and finally the last is pre-incubated with 5 mM of H2O2 and then revealed to be active. Conditions for detecting SOD activity: The activity of purified SOD is measured using the SOD assay kit (19160, Sigma-Aldrich, France). This total SOD activity is greater than 500 IU SOD / mg protein, and the protein content of the purified extract is greater than 70% (Bradford method, Anal. Biochem. 72: 248-54, 1976). After migration, the gels are immersed: - for 150 min in a K+ phosphate buffer (50 mM; pH 7.8) containing 2 mM NBT. - then for 15 min in a K+ phosphate buffer (50 mM; pH 7.8) containing 28 mM TEMED and 0.0028 mM riboflavin (prepare a solution of 50 mg riboflavin in 1 ml of phosphate buffer). The gels are then rinsed in a 50 mM potassium phosphate buffer solution (pH 7.8). The electrophoresis gels are then digitized using the Perfect Image photo capture module and subsequently analyzed by the Gel Analyst analysis module (Claravision, 2000, France). As seen in Figure 1, in the absence of inhibitors, the SOD mixture exhibits two thick bands of SOD activity (well 1), one located towards the top of the gel, indicating high molecular weight proteins (which migrate less quickly than low molecular weight proteins) and one towards the bottom of the gel indicating activity due to one or more low molecular weight SODs. In the presence of 2 mM KCN ​​(well 2), only Cu / Zn-SOD is inhibited, this corresponds to the band located at the bottom of the gel and this represents the greater part of this band of activity. In the presence of 5 mM H₂O₂ (well 3), Fe-SOD and Cu / Zn-SOD are inhibited. The only band remaining on the gel (at the top) corresponds to Mn-SOD (insensitive to KCN and H₂O₂). Mn-SOD represents part of the SOD activity band located at the top of the gel; the other part is Fe-SOD inhibited by H₂O₂. The other form of Fe-SOD is located at the bottom of the gel, near Cu / Zn-SOD. The intensities of the different SOD activity bands are integrated using the Gel Analyst analysis module (Claravision, 2000, France), and the ratio of each SOD isoform is calculated as follows: Intensity of each SOD without Inhibitor bands +KCN +H2O2 1 177 160 173 721 62 124 2,442,524 43,594 / Total 619,684,217,315,621,240 For Mn-SOD (band 3), the band intensity is 62,124 out of a total intensity of 619,684 (SOD without inhibitors), so Mn-SOD represents 10% of the total SOD activity. For Cu / Zn-SOD, the band intensity is (442,524-43,594) / 619,684 and corresponds to 65% of the total activity. Finally, Fe-SOD represents 25%, with one isoform representing 7% (near Mn-SOD) and the other 18% (near Cu / Zn-SOD). The above analyses, carried out on a mixture of SOD extracted from the Fl hybrid variety of Cucumis Melo MA 7950, were carried out under the same conditions on other SODs from different fruits: Anasta melon, Spanish melon (Canary), Clipper melon (descendant of the Fl hybrid variety of Cucumis Melo 95LS444), watermelon, peach, nectarine, cherry (Figures 2 and 3). As can be seen in Figures 2 and 3, the electrophoresis profiles of SOD activities from different fruits are very different from a mixture of purified SOD extracted from the Fl hybrid variety of Cucumis Melo MA 7950 (leftmost). The percentages of each form after use of inhibitors (2 mM KCN ​​and 5 mM H2O2) are reported in Table 1. Table 1: Proportion of different forms of SOD. Cu / Zn-SOD Mn-SOD Fe-SOD Melon MA 7950 65% 10% 25% Watermelon 66% 18% 16% Canary Melon 83% 9% 8% Anasta Melon 84% 13.5% 2.5% Melon Clipper 25% 60% 15% Nectarine 81.5% 0% 18.5% Fishing 88% 0% 12% Cherry 100% 0% 0% Apricot 0% 0% 0% On these same electrophoresis gels, molecular weight markers (proteins of known molecular weight) were introduced into the first well of the gel, using a marker kit (M 3913, Sigma-Aldrich, France) in order to calibrate the gel in molecular weight and to determine by comparison the molecular weights of the different SODs. The same analyses were carried out on mixtures of SOD purified from different fruits, only on fruits containing 3 forms of SOD: watermelon, Spanish melon (Canari), another variety of melon (Anasta). The molecular weights of the different SODs are shown in Table 2. Table 2: Molecular weights of the different forms of SOD extracted from the Fl hybrid variety of Cucumis Melo MA 7950, from watermelon, Canary melon, Anasta melon and Clipper melon (descendant of the Fl hybrid variety of Cucumis Melo 95LS444). Cu / Zn SOD, Mn SOD, Fe SOD Melon MA 7950 31 800 80 600 32 200 79,800 Watermelon 41,600 72,200 56,400 Canary Melon 44,700 65,900 43,700 Anasta Melon 42,600 62,700 44,700 Melon Clipper 40,000 95,000 30,000 It is readily apparent that the purified SOD mixture extracted from the Cucumis Melo MB 17415 hybrid variety is unique (compared to other SODs from different fruits), particularly due to the presence of the second Fe-SOD isoform. It contains three classes of SOD (differentiated by their metal group) and four isoforms: • Cu / Zn-SOD represents 65% of the total SOD activity and has a molecular weight of 31,800 Da. · Mn-SOD represents 10% of the total SOD activity and has a molecular weight of 80,600 Da. • Two different forms of Fe-SOD account for 25% of the total activity: One Fe-SOD transaction of 32,200 DA represents 18% of total SOD activity. The other Fe-SOD transaction of 79,800 DA represents 7% of total SOD activity. Determination of the isoelectric points of the different SODs This analytical technique is useful for obtaining additional information on the pI of SOD isoforms purified from melon. It will therefore be performed in active conditions. The separation of SODs according to their charge is carried out by isoelectric focusing (IEF). SODs migrate in an electric field and become immobilized when the surrounding pH makes their overall charge zero. The isoelectric points of the different SOD forms can be determined on IEF gels by comparison with known isoelectric point markers (IEF markers 3.6-9.3, Reference 56733, Sigma-Aldrich, France). Samples loaded onto gels (acrylamide / acrylamide bis 30%>, glycerol 50%>, ampholines 3.5-10 Amersham, ammonium persulfate, and Temed) migrate at 300 V and 20 mA through a sample buffer (glycerol 75% v / v, ampholines 2% v / v) and a migration buffer (NaOH 25 mM for the cathode and CH3COOH 25 mM for the anode). Isoelectric point markers are also loaded onto a well of the gel. The detection of the SOD activity bands is performed as described in Section 2. By comparison with the pI marker bands, the pIs of the different isoforms are determined. For Anasta melon, the low proportion of Fe-SOD (2.5%) does not allow for the identification of the different pIs. The isoelectric points of the different forms of SOD of the 3 varieties (MA 7950; watermelon, Canary melon) are shown in Table 3. Table 3: Isoelectric points (pHi) of the different forms of SOD extracted from the hybrid variety Fl of Cucumis Melo MA 7950, from watermelon, from Canary melon. Cu / Zn SOD, Mn SOD, Fe SOD Melon MA 7950 4.3 4.1 4.4 4.4 4.7 5.3 5.5 5.7 5.85 6.1 Watermelon 4.6 4.25 4 4.7 4.7 5.2 5.8 6 6.1 Canary Melon 4.4 4.4 4 5.7 5.8 5.9 6 It is noted that the mixture of purified SOD extracted from the Fl hybrid variety of Cucumis Melo MA 7950, characterized by their metal group, molecular weight and pHi, is unique; it contains: • Cu / Zn-SOD represents 65% of the total SOD activity, has a molecular weight of 31,800 Da and a pI of 4.3; • Mn-SOD represents 10% of the total SOD activity, has a molecular weight of 80,600 Da and has 7 different isoforms with pIs between 4 and 6; • Two different forms of Fe-SOD account for 25% of the total activity: A Fe-SOD of 32,200 Da represents 18% of the total SOD activity. The other Fe-SOD, at 79,800 Da, represents 7% of the total SOD activity. They have a pI of 4.4 and 4.7. In 1 mg of the mixture according to the invention, there is approximately 0.71 mg of Cu / Zn SOD, 0.06 mg of Mn-SOD and 0.23 mg of Fe-SOD. Example 4. Efficacy of the mixture of purified SOD according to the invention on an oxidative stress marker: the superoxide anion (0°-) produced by NADPH oxidase, and on an inflammatory marker: TNF-κB In macrophages, the use of molecules such as interferon gamma or LPS makes it possible to induce an oxidative burst (overproduction of the superoxide radical due to stimulation of NADPH oxidase) and an inflammatory response (increased production of TNF a and interleukins). The effect of different doses of a mixture of purified SOD according to the invention on the production of the superoxide radical (O2-), and on the production of an inflammatory cytokine (TNF-α) on a murine macrophage cell line RAW 264.7 was evaluated. The cells are cultured in RPMI (Roswell Park Memorial Institute Medium) supplemented with fetal bovine serum (10%, Life Technologies), a penicillin-streptomycin antibiotic solution (1%, Life Technologies), and fungizone (0.25%), Life Technologies, in 175 cm² T culture dishes (Dutscher, Brumath, France) under a humid atmosphere enriched with 5% CO₂ at 37°C. The cells are counted and subculturated every three days using a Thoma slide and then distributed into culture dishes at a concentration of 250,000 cells / ml. The cells are then incubated with a mixture of purified SOD according to the invention (from 0 to 100 IU SOD / ml) for 12 hours. They are then detached from the support and suspended at a concentration of 10⁶ cells / ml in RPMI. 890 μA of this suspension is placed in the presence of 100 μA of 1 mM lucigenin and incubated at 37°C for 30 minutes.At the end of the 30-minute period and at the time of measurement, 10 μM of PMA (Phorbol-12-Myristyl-13-Acetate, Sigma Chemical; St. Louis, MO; USA) is added to measure superoxide radical production. To stimulate TNF-α production, lipopolysaccharide (LPS) is introduced into the wells 12 hours before measurement. O2- production is measured by a chemiluminescence technique (Chen et al., Am. J. Renal. Physiol. 289 F 749-53 2005) in the presence of lucigenin (10 μM), a bioluminescence probe specific to superoxide radicals. In brief, in the presence of O2, lucigenin transitions from a ground state to an excited state. Upon returning to its ground state, lucigenin emits photons. The quantity of photons emitted is proportional to the O2 formation. The intensity of the luminescence is recorded using a luminescence microplate reader (Synergy 2 Biotek, USA). The results are expressed as counts / mg of protein. TNF-α production in macrophages was measured by ELISA using a DY 510 assay kit (R&D System, Minneapolis, USA). The results are the average of 3 independent replicates. As seen in Tables 4 and 5, the mixture of SODs from the MA 7950 cell line modulates the oxidative and inflammatory response of the murine macrophage cell line by inhibiting the production of the superoxide anion by NADPH oxidase and the production of TNFα. Table 4: Effect of different doses of a mixture of purified SOD extracted from the Fl hybrid variety of Cucumis Melo MA 7950 on superoxide anion production (SOD (Ul / ml) Ô 5 ÏÔ 50 ÏÔÔ % activation 100+ 5 79.5+ 5.5 66.4+ 3.2 30.5+ 2.5 19.6+ 2.4 Table 5: Effect of different doses of the MA 7950 SOD mixture on TNF production (SOD (Ul / ml) Ô 5 ÏÔ 50 ÏÔÔ TNF a (pg / ml) 721± 12 454+17 166+16 69+7 59+5 Example 5: Efficacy of the mixture of purified SOD according to the invention on the endogenous synthesis of antioxidant enzymes A mixture of purified SOD according to the invention was encapsulated according to the process described in international application WO2006030111 to allow oral use. Ten 3-week-old male Wistar rats (from the Janvier breeding facility in Le Genest-St-Isle, France) were used. Upon arrival, they were randomly divided into groups and then housed in plastic cages in a controlled environment with a temperature of 23 ± 1°C, a humidity of 70%, and a 12-hour photoperiod (12 hours of light / 12 hours of darkness). The rats were handled according to NIH (National Research Council) guidelines. The animals have free access to food and water. Food consumption is measured daily and the animals' body weight is recorded every two days. The animals are separated into 2 groups of 5. One group receives the standard regimen (EF R / M control E 15000-00, SSNIFF, Germany). The other group receives the standard regimen (EF R / M control E 15000-00, SSNIFF, Germany) as well as a dose of 4 IU SOD (or U / mg SOD) of the mixture according to the invention per day for 28 days. At the end of the 28-day experiment, the animals were anesthetized by intraperitoneal injection of pentobarbital. The liver was perfused with 0.15M NaCl, then removed and stored at -80°C. The expression of the antioxidant enzymes SOD and GPx was determined by western blot. The results are reported in Table 4. As can be seen, ingestion of the SOD mixture from the MA 7950 melon leads to the induction of the expression of the antioxidant enzymes SOD and GPx in the Wistar rat in the absence of oxidative stress. Table 6: Quantification of SOD and glutathione peroxidase (GPX) expression in the liver of male Wistar rats SOD GPX control animals 100 100 animals treated with a mixture 235+ 8 161+ 5 Purified SOD according to the invention. Under oxidative stress, this pool of antioxidant proteins can then be activated and utilized, enabling a better cellular response to oxidative stress. Example 6: Effect of the SOD mixture according to the invention on the expression of the NPPA and RXFP1 genes. The effect of the mixture of purified SOD according to the invention on genes involved in cardiac hypertrophy was evaluated in a spontaneously hypertensive rat (SHR) model. These are spontaneously hypertensive rats with cardiac hypertrophy, resulting from genetic crosses, which are usable upon receipt and have the advantage of being "ready to use". The various mixtures of purified SOD according to the invention were encapsulated according to the process described in international application WO2006 / 030111 to allow for oral use. Forty 3-week-old male SHR rats (from the Janvier breeding facility in Le Genest-St-Isle, France) were used. Upon arrival, they were randomly divided into groups and then housed in plastic cages in a controlled environment with a temperature of 23 ± 1°C, a humidity of 70%, and a 12-hour photoperiod (12 hours of light / 12 hours of darkness). The rats were handled according to NIH (National Research Council) guidelines. The animals have free access to food and water. Food consumption is measured daily and the animals' body weight is recorded every two days. The animals are separated into 4 groups of 10 (groups 1, 2, 3 and 4). Group 1 receives the standard regimen (EF R / M control E 15000-00, SSNIFF, Germany). Group 2 receives for 4 days the standard diet (EF R / M control E 15000-00, SSNIFF, Germany) as well as a dose of 4 IU SOD (or U / mg SOD) per day of the mixture of SODs from the MA7950 melon according to the invention. Groups 3 and 4 received the standard diet (EF R / M control E 15000-00, SSNIFF, Germany) for 4 days, along with a daily dose of 4 IU SOD (or U / mg SOD) of the SOD mixture from Canary melon (group 3) or Anasta (group 4). At the end of the 4-day experiment, the animals were anesthetized by intraperitoneal injection of pentobarbital. The heart was removed, and GANP and RXFP1 levels were measured by Western blot in the left ventricle (LV). Protein extraction from glycine-glycine (VG) was performed in ice with 20 mM Tris buffer (pH 6.8) containing 150 mM NaCl, ImM EDTA, 1% Triton 20%, 0.1% SDS, and 1% protease inhibitor cocktail. After centrifugation (1500 rpm, 15 min at 4°C), the supernatant was collected, and the tissue proteins were separated by SDS-PAGE. An equivalent amount of protein was loaded onto 10% or 15% acrylamide gels with a 4% acrylamide gel. Migration was performed in Tris-glycine-SDS buffer from Sigma-Aldrich (Saint Quentin Fallavier, France). After separation, the proteins were transferred to nitrocellulose membranes (Whatman, Dassel, Germany). Quantification was performed after standardization in the membranes by expressing the density of each band of interest relative to GAPDH in a single row. The results are then expressed as relative changes compared to the placebo group. ** p<0.01 compared to the placebo group. The results are shown in Table 7 below. Table 7: Quantification of GANP and RXFP1 expression in the heart of SHR rats. ANP RXFP1 Control Animals 100 100 Animals treated with SOD mixture from melon MA7950 Animals treated with a mixture of SOD derived from Canary melon (NS) (NS) Animals treated with SOD mixture issues 97 96 Anasta melon (NS) (NS) (NS): not significant; **: significant As shown in Table 7 above, only the ingestion of the SOD mixture from the MA 7950 melon (SOD mixture according to the invention) results in a modulation of the expression of ANP and RXFP1 proteins, whose NPPA and RXFP1 genes are implicated in cardiovascular diseases, particularly cardiac hypertrophy, and obesity. This modulation, as explained above, is beneficial in the case of cardiovascular diseases (decreased ANP concentration and increased RXFP1 concentration). Printed (original in electronic form) (This sheet is not part of the international application nor does it count as a sheet thereof) of the agent 1 The indications below relate to to the microorganism or other material biological material referred to in the description: 1-1 page 6 1-2 line 24 1-3 Identification of the deposit 1-3-1 Name of the depository institution NCIMB National Collections of Industrial, Food and Marine Bacteria (NCIMB) 1-3-2 Address of the depository institution: NCIMB Ltd, Ferguson Building, Craibstone Estate, Bucksburn, Aberdeen AB21 9YA, United Kingdom 1-3-3 Filing date: July 17, 2013 (17.07.2013) 1-3-4 Order number NCIMB 42154 1-5 designated States for which the Indications are given for all the designations RESERVED FOR THE RECEIVING OFFICE 0-4 This sheet was received at the same time while international demand (yes or no) yes 0-4-1 Authorized Official Isabelle Aoustin FOR INTERNATIONAL OFFICE USE ONLY 0-5 This sheet has reached the Office international le: 0-5-1 Authorized Official

Claims

Demands 1. Mixture of superoxide dismutases of plant origin, characterized in that it consists essentially of 3 superoxide dismutases: a manganese superoxide dismutase, a copper and zinc superoxide dismutase and an iron superoxide dismutase present in at least two isoforms, the first iron superoxide dismutase isoform with a molecular weight between 28,000 and 36,000 Da, the second iron superoxide dismutase isoform with a molecular weight between 75,000 and 85,000 Da, said mixture being capable of being obtained from an extract of the Fl hybrid variety of Cucumis Melo MA 7950 or from its cells cultured in vitro or by transfer and expression of the genes of these SODs in prokaryotic or eukaryotic cells.

2. Mixture of superoxide dismutases according to claim 1, characterized in that said mixture has a total SOD activity greater than or equal to 130 U / mg of said mixture.

3. Mixture of superoxide dismutases according to claim 1 or 2, characterized in that the first iron superoxide dismutase isoform has a molecular weight of about 32,200 Da.

4. Mixture of superoxide dismutases according to any one of claims 1 to 3, characterized in that the second iron superoxide dismutase isoform has a molecular weight of about 79,800 Da.

5. Mixture of superoxide dismutases according to any one of claims 1 to 4, characterized in that the cumulative SOD activity of the two iron superoxide dismutase isoforms is between 20% and 26%, advantageously between 22% and 26% of the total SOD activity of the mixture.

6. Mixture of superoxide dismutases according to any one of claims 1 to 5, characterized in that the cumulative SOD activity of the two iron superoxide dismutase isoforms is between 20% and 26% of the total SOD activity of the mixture, the activity of copper and zinc superoxide dismutase is between 60% and 70% of the total SOD activity of the mixture, and the activity of manganese superoxide dismutase is between 7% and 12% of the total SOD activity of the mixture.

7. Mixture of superoxide dismutases according to any one of claims 1 to 6, characterized in that the manganese superoxide dismutase has a molecular weight between 70,000 and 90,000 Da and the copper and zinc superoxide dismutase has a molecular weight between 27,000 and 33,000 Da.

8. Mixture of superoxide dismutases according to any one of claims 1 to 7, characterized in that it is capable of being obtained by grinding or pressing in aqueous medium, preferably at pH 5 to 9, of the hybrid variety Fl of Cucumis Melo MA 7950 or of its cells cultured in vitro or by transfer and expression of the genes of these SODs in prokaryotic or eukaryotic cells and then recovery of the supernatant and purification by chromatography, in particular by IMAC chromatography.

9. Nutritional, cosmetic or pharmaceutical composition containing as an active ingredient a mixture of superoxide dismutases according to any one of claims 1 to 7 and at least one food, pharmaceutically or cosmetically acceptable excipient.

10. A cosmetic composition according to claim 9, characterized in that it is intended for external topical use, such as skincare products, shampoos, lotions, and gels.

11. A pharmaceutical composition according to claim 9, characterized in that it is intended for administration by topical, oral, nasal, or parenteral routes, and is presented, for example, in the form of a tablet, capsule, softgel, effervescent tablet, sachet or stick for dilution, syrup, elixir, herbal tea, chewing gum, spray, aerosol, or injectable solution.

12. A pharmaceutical composition according to claim 9 or 11, characterized in that it contains another active ingredient, advantageously another antioxidant.

13. Pharmaceutical composition according to any one of claims 9, 11 or 12 for its use as a medicinal product.

14. Pharmaceutical composition for use according to claim 13, characterized in that the medicinal product is intended to treat or prevent diseases related to oxidative stress and / or inflammation and / or to enhance the action of other pharmaceutical molecules, and in particular other antioxidants used, or to treat orphan diseases, in an animal.

15. Pharmaceutical composition for use according to claim 14, characterized in that the drug is intended to stimulate cell vitality in an animal.

16. Pharmaceutical composition for use according to claim 14 or 15, characterized in that the animal is man.

17. Pharmaceutical composition for use according to claim 13, characterized in that the medicinal product is intended for the treatment of cardiovascular diseases, obesity, arteriosclerosis, and herpes labialis, particularly in humans.

18. Nutritional composition according to claim 9, characterized in that it is intended for oral administration and is presented for example in the form of a tablet, capsule, soft capsule, effervescent tablet, sachet or stick to be diluted, chewing gum, beverages, juice, yogurt, confectionery, biscuit or bars.