COMPOSITION COMPRISING A MIXTURE OF PLANT EXTRACTS OR A MIXTURE OF MOLECULES CONTAINED IN THESE PLANTS AND USE FOR ACTING ON CARBOHYDRATE AND / OR LIPID METABOLISM

Abstract

The object of the invention is a composition comprising at least one mixture of molecules obtained at least from: - <em>Chrysanthelum indicum< / em> , And - <em> cynara scolymus< / em> , And - <em> vaccinium myrtillus< / em> This mixture of molecules also includes piperine. This composition is particularly useful as a nutritional or health product to prevent and / or combat disorders of carbohydrate and / or lipid metabolism in humans or animals.

Description

[0001] The present invention relates to the prevention and treatment of disorders of carbohydrate and / or lipid metabolism in humans or animals.

[0002] Type 2 diabetes, the most common form of diabetes, is a chronic, progressive metabolic disease. It is characterized by chronic hyperglycemia, meaning abnormally high blood sugar levels, and glucose intolerance. The main cause of this chronic hyperglycemic state is insulin resistance and inadequate insulin secretion in response to a given metabolic state, but other factors can also play a role (Ismail-Beigi FN Engl J Med 2012; 366:1319-27). Managing type 2 diabetes primarily involves reducing blood glucose levels, lowering glycated hemoglobin (HbA1c) to 6.5% or lower, and improving insulin sensitivity.

[0003] The treatment of type 2 diabetes primarily involves lifestyle modifications, or dietary and lifestyle changes (DSCs: diet, smoking, physical activity, and exercise). If DSCs are insufficient, then antidiabetic medications, usually metformin, may be prescribed. However, metformin has numerous medical contraindications, such as chronic kidney disease, acidosis, hypoxia, dehydration, etc. This presents a significant paradox: metformin cannot be prescribed to type 2 diabetic patients with kidney disease, yet kidney disease is a frequent consequence of type 2 diabetes.Other therapeutic agents have been developed, such as dipeptidyl peptidase-IV (DPP-IV) inhibitors, glucagon-like peptide-1 (GLP-1) analogs, thiazolidinediones (TZDs), sulfonylureas, glycosidase inhibitors (acarbose, miglitol, voglibose), and sodium glucose cotransporter-2 (SGLT2) inhibitors. However, finding the right therapeutic combination is complex because it requires consideration of a significant number of factors, including contraindications and adverse effects, which impact patients' quality of life and therefore their adherence to medical treatment. Furthermore, some therapeutic combinations increase all-cause mortality, such as the combination of metformin with sulfonylureas (Prescrire Int 2015; 24:130-5).

[0004] Since MHDs are very rarely followed by patients, it is necessary to very quickly initiate therapeutic treatment with all the undesirable effects and contraindications linked to these molecules, and there is currently no suitable solution for the management of type 2 diabetic patients between MHDs and the initiation of therapeutic treatment.

[0005] Furthermore, patients with type 2 diabetes have a high risk of cardiovascular morbidity and mortality. It is therefore also necessary to manage traditional cardiovascular risk factors, such as controlling circulating lipids, weight, and blood pressure. This necessity currently leads to the simultaneous use of several medications from different therapeutic classes. However, drug combinations can sometimes cause serious side effects, such as the simultaneous administration of fibrates and statins, which increases the risk of myopathy (Denke MA J Manag Care Pharm 2003; 9:17-9).

[0006] There is therefore a real need for products that can be used both during the gradual onset of cardiometabolic diseases, characterized by an increase in certain risk factors (carbohydrate disorders, lipid disorders, overweight, inflammation, oxidative stress, high blood pressure), and during the onset of these diseases, particularly type 2 diabetes.

[0007] Furthermore, there is an urgent need for preventative solutions and medications with a multi-targeted mechanism of action that offers advantages in terms of compliance, tolerability, and efficacy. Such products would reduce the overall risk of cardiometabolic diseases and prevent and treat each dysfunction and / or its consequences independently.

[0008] The objective of the invention is to meet these different needs by offering compositions capable of acting simultaneously on several carbohydrate and lipid dysfunctions, which represent both a means of prevention and an advantageous therapeutic means for preventing and treating cardiometabolic diseases and their complications.

[0009] To achieve its objective, the invention aims at compositions comprising at least one mixture of molecules consisting of at least: an excerpt from Chrysanthemum indica, and an excerpt from Cynara scolymus, and an excerpt from Vaccinium bilberry, and synthetic piperine and / or an extract of Peppercontaining piperine, said mixture of molecules comprising: at least one molecule selected from apigenin-7-O-glucuronide, chrysanthellin A, chrysanthellin B, caffeic acid, luteolin, maritimetin, eriodictyol, isokanine, apigenin, luteolin-7-O-glucoside, maritimein, marein, eriodictyol-7-O-glucoside, flavomarein, apigenin-8-C-α-L-arabinoside-6-C-β-D-glucoside (shaftoside), apigenin-6,8-C-di-β-D-glucopyranoside (vicenin-2), and at least one molecule selected from dicaffeoylquinic acid, sulfo-monocaffeoylquinic acid, luteolin, the luteolin-7-O-glucoside, luteolin-7-O-glucuronide, apigenin-7-O-glucoside, cynaropicrin, and at least one molecule selected from monocafeoylquinic acid, delphinidine-3-galactoside, delphinidine-3-glucoside, cyanidin-3-galactoside, delphinidine-3-arabinoside, cyanidin-3-glucoside, petunidin-3-galactoside, cyanidin-3-arabinoside,petunidin-3-glucoside, peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, and at least piperine.

[0010] This is a synergistic mixture, the molecules present in the mixture acting in synergy.

[0011] Excerpts from Chrysanthemum indica, excerpts from Cynara scolymus, excerpts from Blueberry and la piperine have already been described and some have been used in nutritional products, but unexpectedly the combination of at least one extract of Chrysanthemum indica, with at least one extract from Cynara scolymus, an excerpt from Bilberry blueberry and de la piperine leads to surprising results on both carbohydrate and lipid metabolism in humans and animals.

[0012] To achieve its objective, the invention also targets compositions consisting of at least piperine and specific molecules contained in Chrysanthellum indicum, Cynara scolymus And Bilberry(these molecules being natural and / or synthetic), in particular a composition comprising a mixture of at least four molecules, at least one molecule being piperine, at least one molecule being selected from apigenin-7-O-glucuronide, chrysanthellin A, chrysanthellin B, caffeic acid, luteolin, maritimetin, eriodictyol, isokanine, apigenin, luteolin-7-O-glucoside, maritimein, marein, eriodictyol-7-O-glucoside, flavomarein, apigenin-8-C-α-L-arabinoside-6-C-β-D-glucoside (shaftoside), apigenin-6,8-C-di-β-D-glucopyranoside (vicenin-2), or their analogues, and at least one molecule being selected from a dicaffeoylquinic acid, a sulfo-monocaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, apigenin-7-O-glucoside, cynaropicrin or their analogues, and at least one molecule being selected from a monocafeoylquinic acid, delphinidine-3-galactoside,delphinidin-3-glucoside, cyanidin-3-galactoside, delphinidin-3-arabinoside, cyanidin-3-glucoside, petunidin-3-galactoside, cyanidin-3-arabinoside, petunidin-3-glucoside, peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, or their analogues.

[0013] In this application, the singular or plural shall be used interchangeably to refer to the compositions according to the invention.

[0014] Advantageously, the compositions according to the invention prevent the development of chronic hyperglycemia and lower blood glucose levels, reduce glycated hemoglobin, improve tolerance to ingested carbohydrates, and enhance insulin sensitivity. They are also capable of acting on other cardiovascular risk factors such as dyslipidemia, overweight and obesity, and blood pressure. Furthermore, they exhibit few or no side effects compared to those observed with existing and developing treatments.

[0015] The invention therefore also aims at the use of the compositions as nutritional or health products, in particular as medicines, especially to prevent and / or combat disorders of carbohydrate and lipid metabolism in humans or animals.

[0016] The invention is now described in detail with reference to the accompanying figures, which represent: Figure 1 : the results for four compositions of an oral insulin sensitivity test corresponding to the results in Table 9 (item II.1). Figure 2 : the results demonstrating the synergistic effect provided by a composition according to the invention, these results corresponding to the results of Table 13 (point II.1) for fasting blood glucose. Figure 3 : the results demonstrating the synergistic effect provided by a composition according to the invention, these results corresponding to the results of Table 13 (point II.1) for carbohydrate tolerance. Figure 4 : the results demonstrating the synergistic effect provided by a composition according to the invention, these results corresponding to the results of Table 14 (point II.1) for fasting blood glucose. Figure 5: the results demonstrating the synergistic effect provided by a composition according to the invention, these results corresponding to the results of Table 14 (point II.1) for carbohydrate tolerance. Figure 6 : the results demonstrating the synergistic effect provided by a composition according to the invention, these results corresponding to the results of Table 14 (point II.1) for insulin sensitivity. Figure 7 : the results for the effect of a composition according to the invention and metformin, on insulin sensitivity, these results corresponding to the results of Table 15 (point II.2). Figure 8 : the results for the effect of a composition according to the invention on the evolution of body mass, these results corresponding to the results of table 15 (point II.2). Figure 9 : the results for the effect of a composition according to the invention on the evolution of fasting blood glucose, these results corresponding to the results of Table 15 (point II.2). Figure 10: the results of a western blot showing an increase in the amount of AMPK in the liver of mice with a composition according to the invention (point 11.2). Figure 11 : the results of tests showing the absence of an acute hypoglycemic effect with a composition according to the invention (point II.3).

[0017] The invention relates to a composition comprising at least one mixture of molecules consisting of at least: an excerpt from Chrysanthemum indica, and an excerpt from Cynara scolymus, and an excerpt from Vaccinium bilberry, and synthetic piperine and / or an extract of Peppercontaining piperine, said mixture of molecules comprising: at least one molecule selected from apigenin-7-O-glucuronide, chrysanthellin A, chrysanthellin B, caffeic acid, luteolin, maritimetin, eriodictyol, isokanine, apigenin, luteolin-7-O-glucoside, maritimein, marein, eriodictyol-7-O-glucoside, flavomarein, apigenin-8-C-α-L-arabinoside-6-C-β-D-glucoside (shaftoside), apigenin-6,8-C-di-β-D-glucopyranoside (vicenin-2), and at least one molecule selected from dicaffeoylquinic acid, sulfo-monocaffeoylquinic acid, luteolin, the luteolin-7-O-glucoside, luteolin-7-O-glucuronide, apigenin-7-O-glucoside, cynaropicrin, and at least one molecule selected from monocafeoylquinic acid, delphinidine-3-galactoside, delphinidine-3-glucoside, cyanidin-3-galactoside, delphinidine-3-arabinoside, cyanidin-3-glucoside, petunidin-3-galactoside, cyanidin-3-arabinoside,petunidin-3-glucoside, peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, and at least piperine.

[0018] The invention therefore relates to a composition comprising at least piperine, at least one molecule derived from Chrysanthemum indica, at least one molecule derived from Cynara scolymus and at least one molecule derived from Vaccinium bilberry.

[0019] In addition to Chrysanthemum indica, of Cynara scolymus, of Bilberry and piperine; the composition according to the invention may also contain other compounds, in particular an extract of European olive. In this case, the composition according to the invention comprises at least one molecule derived from Chrysanthemum indica, at least one molecule derived from Cynara scolymus, at least one molecule derived from Bilberry and at least one molecule derived from European olive tree and piperine.

[0020] The composition according to the invention comprises at least: an excerpt from Chrysanthemum indica, and an excerpt from Cynara scolymus, and an excerpt from Vaccinium bilberry, and synthetic piperine and / or an extract of Pepper containing piperine.

[0021] For the purposes of this invention, plant extract "X" or plant raw material "X" means at least one molecule, preferably a set of molecules, obtained from plant "X" by any suitable process. Examples include aqueous extracts (obtained using an aqueous solvent), alcoholic extracts (obtained using an alcoholic solvent), extracts using an organic solvent, or extracts using a natural fat or a mixture of natural fats, particularly a vegetable oil or a mixture of vegetable oils. An aqueous solvent means any solvent consisting wholly or partly of water. Examples include water itself, hydro-alcoholic solvents in any proportion, or solvents consisting of water and a compound such as glycerin or propylene glycol in any proportion. Ethanol is a notable example of an alcoholic solvent.

[0022] Plant or plant raw material within the meaning of the invention means the whole plant or part of a plant, including cell cultures, which has not yet undergone specific treatment and is intended to be used in the manufacture of a plant preparation.

[0023] Plant extracts can be obtained by any suitable process, for example by a process comprising the following steps: solid / liquid extraction separation / pressing filtration evaporation drying possibly incorporation of additives homogenization packaging.

[0024] The excerpt from Chrysanthemum indica is preferably an extract of the whole plant or aerial parts.

[0025] This may include, in particular, a hydroalcoholic or aqueous extract, subcritical CO2, subcritical H2O, or a heat treatment carried out by conventional heating, microwave frequency, or ultrasound.

[0026] The plant / extract ratio is preferably between 1 / 1 and 100 / 1, in particular between 1 / 1 and 25 / 1.

[0027] The composition according to the invention, when intended for human use, preferably comprises a quantity of extract of Chrysanthemum indica allowing the administration of at least 0.00001g, in particular between 0.00001g and 0.60g, of extract of Chrysanthemum indica per kg of body weight of the person to whom the composition is administered and per day.

[0028] Preferably, the extract from Chrysanthemum indicacomprises at least one molecule selected from apigenin-7-O-glucuronide, chrysanthellin A, chrysanthellin B, caffeic acid, luteolin, maritimetin, eriodictyol, isokanine, apigenin, luteolin-7-O-glucoside, maritimein, marein, eriodictyol-7-O-glucoside, flavomarein, apigenin-8-C-α-L-arabinoside-6-C-β-D-glucoside (shaftoside), apigenin-6,8-C-di-β-D-glucopyranoside (vicenin-2), or their analogues. Preferably, the extract comprises at least apigenin-7-O-glucuronide.

[0029] Analogues, as defined in the present invention, are all compounds having a chemical structure similar to another compound, but differing from it by a certain component. It may differ by one or more atoms, functional groups, or substructures, which are replaced by other atoms, functional groups, or substructures. Examples of analogs of apigenin-7-O-glucuronide include apigenin-7-apioglucoside, apigenin-8-C-glucoside (vitexin), apigenin-6-C-glucoside (isovitexin), apigenin-7-O-neohesperidoside, apigenin-7-glucoside, and apigenin-7-apioglucoside.

[0030] The excerpt from Cynara scolymus is preferably an extract of leaves or roots.

[0031] This may include, in particular, a hydroalcoholic or aqueous extract, subcritical CO2, subcritical H2O, or a heat treatment carried out by conventional heating, microwave frequency, or ultrasound.

[0032] The plant / extract ratio is preferably between 1 / 1 and 100 / 1, in particular between 1 / 1 and 30 / 1.

[0033] The composition according to the invention, when intended for human use, preferably comprises a quantity of extract of Cynara scolymus allowing the administration of at least 0.00001g, in particular between 0.00001g and 0.60g, of extract of Cynara scolymus per kg of body weight of the person to whom the composition is administered and per day.

[0034] Preferably, the extract from Cynara scolymus comprises at least one molecule selected from dicaffeoylquinic acid, sulfo-monocaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, apigenin-7-O-glucoside, cynaropicrin, or their analogues. Preferably, the extract comprises at least one dicaffeoylquinic acid.

[0035] The excerpt from Bilberry is preferably an extract of fruits or leaves.

[0036] This may include, in particular, a hydroalcoholic or aqueous extract, subcritical CO2, subcritical H2O, or a heat treatment carried out by conventional heating, microwave frequency, or ultrasound.

[0037] The plant / extract ratio is preferably between 1 / 1 and 200 / 1, in particular between 1 / 1 and 60 / 1.

[0038] The composition according to the invention, when intended for human use, preferably comprises a quantity of extract of Bilberry allowing the administration of at least 0.00001g, in particular between 0.00001g and 0.60g, of extract of Bilberry per kg of body weight of the person to whom the composition is administered and per day.

[0039] Preferably, the extract from Bilberrycomprises at least one molecule selected from monocafeoylquinic acid, delphinidin-3-galactoside, delphinidin-3-glucoside, cyanidin-3-galactoside, delphinidin-3-arabinoside, cyanidin-3-glucoside, petunidin-3-galactoside, cyanidin-3-arabinoside, petunidin-3-glucoside, peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, or their analogues. Preferably, the extract comprises at least one monocafeoylquinic acid.

[0040] The piperine present in the composition according to the invention may be contained in an extract of Pepper or it could be a synthetic piperine.

[0041] The topological formula of piperine is as follows:

[0042] The composition according to the invention, when intended for human use, preferably comprises an amount of piperine allowing the administration of at least 0.001 mg, in particular between 0.001 mg and 166 mg, of piperine per kg of body weight of the person to whom the composition is administered and per day.

[0043] If piperine is contained in an extract of Pepper, The mixture of the composition according to the invention comprises said extract. The extract of Pepper is preferably an extract from Black pepper, of Hooked pepper and / or Long pepper.

[0044] The excerpt from Pepper is preferably an extract of fruits or leaves.

[0045] This may include, in particular, a hydroalcoholic or aqueous extract, subcritical CO2, subcritical H2O, or a heat treatment carried out by conventional heating, microwave frequency, or ultrasound.

[0046] The plant / extract ratio is preferably between 1 / 1 and 10000 / 1, in particular between 1 / 1 and 200 / 1.

[0047] The extract preferably comprises at least 1% piperine by weight relative to the total weight of the extract.

[0048] Also, the mixture of the composition according to the invention comprises: at least one piperine molecule, and at least one molecule selected from apigenin-7-O-glucuronide, chrysanthellin A, chrysanthellin B, caffeic acid, luteolin, maritimetin, eriodictyol, isokanine, apigenin, luteolin-7-O-glucoside, maritimein, marein, eriodictyol-7-O-glucoside, flavomarein, apigenin-8-C-α-L-arabinoside-6-C-β-D-glucoside (shaftoside), apigenin-6,8-C-di-β-D-glucopyranoside (vicenin-2), or their analogues, preferably apigenin-7-O-glucuronide, and at least one molecule selected from dicaffeoylquinic acid, an acid sulfo-monocaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, apigenin-7-O-glucoside, cynaropicrin, or their analogues, preferably a dicaffeoylquinic acid, and at least one molecule selected from a monocafeoylquinic acid, delphinidine-3-galactoside, delphinidine-3-glucoside, cyanidin-3-galactoside, delphinidine-3-arabinoside,cyanidin-3-glucoside, petunidin-3-galactoside, cyanidin-3-arabinoside, petunidin-3-glucoside, peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, or their analogues, preferably at least one monocafeoylquinic acid.

[0049] In addition to the extracts from Chrysanthellum indicum, of Cynara scolymus and Vaccinium myrtillus, and piperine; the mixture according to the invention may also contain other compounds, in particular an extract of Olea europaea.

[0050] The excerpt from Olea europaea is preferably an extract of leaves or fruits.

[0051] This may include, in particular, a hydroalcoholic or aqueous extract, subcritical CO2, subcritical H2O, or a heat treatment carried out by conventional heating, microwave frequency, or ultrasound.

[0052] The plant / extract ratio is preferably between 1 / 1 and 200 / 1, in particular between 1 / 1 and 60 / 1.

[0053] The composition according to the invention, when intended for human use, preferably comprises a quantity of extract of Olea europaea allowing the administration of at least 0.00001g, in particular between 0.00001g and 0.60g, of extract of Olea europaea per kg of body weight of the person to whom the composition is administered and per day.

[0054] Preferably, the extract from Olea europaea includes at least one molecule chosen from oleuropein and hydroxytyrosol, or their analogues.

[0055] For the purposes of this invention, a mixture is defined as a combination of substances (extracts and / or molecules) in solid, liquid, or gaseous form, which may or may not interact chemically. The mixture of extracts according to the invention is obtained by any process known to those skilled in the art. It may be obtained by simply mixing the constituents.

[0056] Preferably, the ratio extracted from Chrysanthellum indicum / excerpt from Cynara scolymus / excerpt from Vaccinium myrtillus / piperine in the mixture is between 0.01 / 0.01 / 0.01 / 0.0001 and 10 / 10 / 10 / 10.

[0057] The composition according to the invention, comprising plant extracts, therefore includes: at least one molecule chosen from apigenin-7-O-glucuronide, chrysanthellin A, chrysanthellin B, caffeic acid, luteolin, maritimetin, eriodictyol, isokanine, apigenin, luteolin-7-O-glucoside, maritimein, marein, eriodictyol-7-O-glucoside, flavomarein, apigenin-8-C-α-L-arabinoside-6-C-β-D-glucoside (shaftoside), apigenin-6,8-C-di-β-D-glucopyranoside (vicenin-2), or analogues, preferably apigenin-7-O-glucuronide, and from a dicaffeoylquinic acid, a sulfo-monocaffeoylquinic acid, the luteolin, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, apigenin-7-O-glucoside, cynaropicrin, or their analogues, preferably a dicaffeoylquinic acid, and at least one molecule selected from a monocafeoylquinic acid, delphinidine-3-galactoside, delphinidine-3-glucoside, cyanidin-3-galactoside, delphinidine-3-arabinoside, cyanidin-3-glucoside, petunidin-3-galactoside,cyanidin-3-arabinoside, petunidin-3-glucoside, peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, or their analogues, preferably at least one monocafeoylquinic acid, and , at least piperine, and possibly, preferably at least one molecule chosen from oleuropein, hydroxytyrosol, or their analogues.

[0058] According to another aspect, the invention also relates to a composition comprising a mixture of at least four molecules, these molecules being able to be synthetic molecules and / or natural molecules, in particular derived from plant raw materials: at least one molecule being selected from apigenin-7-O-glucuronide, chrysanthellin A, chrysanthellin B, caffeic acid, luteolin, maritimetin, eriodictyol, isokanine, apigenin, luteolin-7-O-glucoside, maritimein, marein, eriodictyol-7-O-glucoside, flavomarein, apigenin-8-C-α-L-arabinoside-6-C-β-D-glucoside (shaftoside), apigenin-6,8-C-di-β-D-glucopyranoside (vicenin-2), or their analogues, and at least one molecule being selected from dicaffeoylquinic acid, sulfo-monocaffeoylquinic acid, luteolin, the luteolin-7-O-glucoside, luteolin-7-O-glucuronide, apigenin-7-O-glucoside, cynaropicrin, or their analogues, and at least one molecule being selected from monocafeoylquinic acid, delphinidine-3-galactoside, delphinidine-3-glucoside, cyanidin-3-galactoside, delphinidine-3-arabinoside, cyanidin-3-glucoside, petunidin-3-galactoside, cyanidin-3-arabinoside, petunidin-3-glucoside,Peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, or their analogues, and at least piperine.

[0059] At least one of the first three molecules is a synthetic molecule. Indeed, apart from piperine, which can be synthetic or natural, at least one of the other molecules is a synthetic molecule.

[0060] In addition to these at least four molecules, the mixture may also include at least one molecule chosen from oleuropein, hydroxytyrosol, or their analogues, these molecules being either synthetic or natural molecules.

[0061] According to a particularly suitable embodiment, the mixture comprises at least one dicaffeoylquinic acid, apigenin-7-O-glucuronide, one monocafeoylquinic acid, piperine, and oleuropein. The mixture of molecules of the composition according to the invention may consist exclusively of one dicaffeoylquinic acid, apigenin-7-O-glucuronide, one monocafeoylquinic acid, piperine, and oleuropein.

[0062] According to other embodiments, the compositions according to the invention may comprise a mixture of extract(s) and molecule(s) of interest presented in this application (for example, an extract of Chrysanthellum indicum) and at least one molecule being selected from dicaffeoylquinic acid, sulfo-monocaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, apigenin-7-O-glucoside, cynaropicrin, or their analogues, and at least one molecule being selected from monocafeoylquinic acid, delphinidine-3-galactoside, delphinidine-3-glucoside, cyanidine-3-galactoside, delphinidine-3-arabinoside, cyanidine-3-glucoside, petunidin-3-galactoside, cyanidine-3-arabinoside, petunidin-3-glucoside, peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, the malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, or their analogues and at least piperine, etc.)

[0063] The compositions according to the invention, in their various versions, may consist exclusively of the elements described (plant extracts and / or a mixture of at least four molecules), or may also include at least one additional element (products, molecules, extracts, active ingredients, excipients, etc.) added in addition to the plant extracts and / or the single extract(s) or the mixture of at least four molecules, said additional element being selectable from: the following vitamins: B1, B2, B3, B5, B6, B8, B9, B12, C, A, D, E, K1 and K2; the following compounds: obeticholic acid, corosolic acid, polyunsaturated fatty acids of the omega 6 and / or omega 3 family, orotic acid, pangamic acid, para-aminobenzoic acid, amygdalin, beta-glucans, carnitine, dimethylglycine, imeglimin, isoflavones, L-arginine, oxytocin, pectin, pyridoxamine, resveratrol, viniferine, L-citrulline; the following trace elements and minerals: arsenic, boron, calcium, copper, iron, fluorine, iodine, lithium, manganese, magnesium, molybdenum, nickel, phosphorus, selenium, vanadium, zinc; the following non-essential microconstituents: conjugated linolenic acid, lipoic acid, carotenoids, carnitine, choline, coenzyme Q10, phytosterols, polyphenols of the tannin and lignan families, taurine; fructo-oligosaccharides, galacto-oligosaccharides; lactic acid bacteria; yeasts, for example red yeast rice ( Monascus purpureus ); mushrooms, for example maitake; insect-derived products compatible with the food and pharmaceutical sectors; marijuana and hashish; coating agents: for example hypromellose, microcrystalline cellulose, stearic acid, talc, sugar, shellac, povidone, beeswax; flavorings: for example natural blueberry flavoring or natural strawberry flavoring; acidifiers such as malic acid; anti-caking agents: for example silicon dioxide or magnesium stearate; thickeners such as xanthan gum, colloidal silica, mono- and diglycerides of fatty acids; stabilizers such as calcium phosphate; emulsifiers such as soy lecithin; bulking agents such as corn starch; excipients: for example microcrystalline cellulose, magnesium stearate or dicalcium phosphate.

[0064] The compositions according to the invention may also include one or more extracts of at least one of the following plant raw materials and / or one or more molecules contained in at least one of the following plant materials: Abelmoschus esculentus, Abies Alba, Abies balsamea, Abies sibirica, Acacia nilotica, Acacia senegal, Achillea millefollium, Achyranthes bidentata, Acmella oleracea, Actaea racemosa, Actinidia chinensis, Actinidia deliciosa, Adansonia digitata, Adiantum capillus-veneris, Aesculus hippocastanum, Aphromum melegueta, Agathosma betulina, Agathosma crenulata, Agathosma serratifolia, Agrimonia eupatoria, Ajuga reptans, Albizia julibrissin, Alchemilla vulgaris, Alliara petiolata, Allium ampeloprasum, Allium cepa, Allium sativum, Allium schoenoprasum, Allium ursinum, Alnus glutinosa, Aloe ferox, Aloe vera, Aloysia citriodora, Alpinia galanga, Alpinia hainanensis, Alpinia officinarum, Alpinia oxyphylla, Althaea officinalis, Ammi visnaga, Amorphophallus konjac, Ananas comosus, Andographis paniculata, Anemarrhena asphodeloides, Anethum graveolens, Angelica archangelica, Angelica dahurica, Angelica pubescens, Angelica sinensis, Antennaria diocia, Anthriscus cerefolium, Anthyllis vulneraria,Aphanizomenon flos-aquae Ralfs, Apium graveolens, Arachis hypogaea, Aralia elata, Arctium lappa, Arctium minus, Argania spinosa, Armorica rustanica, Artemisia dracunculus, Artemesia vulgaris, Ascophyllum nodosum, Aspalathus linearis, Asparagus officinalis, Astragalus membranaceus, Atractylodes lancea, Atractylodes macrocephala, Auracaria columnaris, Avena, Staiva, Ayahuasca, Baccharis genistelloides, Bacopa monnierri, Ballota nigra, Bambusa bambos, Bellis perennis, Berberis vulgaris, Beta vulgaris, Betula alleghaniensis, Betula pendula, Betula pubescens, Bixa orellana, Borago officinalis, Boswellia serrata, Brassica napus, Brassica nigra, Brassica oleracea, Brassica rapa, Bupleurum chinense, Calendula officinalis, Calluna vulgaris, Camellia sinsensis, Capsella bursa-pastoris, Capsicum annuum, Carex arenaria, Carica papaya, Carlina acaulis, Carphephorus odoratissmus, Carpinus betulus, Carthamus tinctorius, Carum carvi, Cassia fistula, Castanea sativa, Centaurea centaurium, Centaurea cyanus, Centaurium erythraea, Centella asiatica, Cerasus vulgaris, Ceratonia siliqua, Chaenomelum nobile, Chlorella vulgaris, Chondrus crispus, Chrysanthellum indicum, Cichorium intybus, Cinchona officinalis, cinchona pubescens, Cinnamomum camphora, Cinnamomum cassia, Cinnamomum verum, Cistanche salsa, Cistus incanus, Citrus aurantium, Citrus limon, Citrus maxima, Citrus medica,Citrus myrtifolia, Citrus reticulata blanco, Citrus sinsensis, Citrus paradisi, Clinopodium vulgare, Cnicus benedictus, Cochlearia officinalis, Cocos nucifera, Codonopsis pilosula, Coffea canephora, Coix lacryma-jobi var. mayyuen Stapf, Cola acuminata, Cola ballayi cornu, Cola nitida, Combretum micranthum, Commiphora mukul, Conyza canadensis, Coriandrum sativum, Cornus officinalis, Corylus avellana, Corymbia citriodora, Crataegus laevigata, Craetegus monogyna, Crithmum maritimum, Crocus sativus, Cucumis melo, Cucurbita pepo, Cuminum cyminum, Cupressus sempervirens, Cuscuta chinensis, Cyamopsis tetragonoloba, Cyathula officinalis, Cyclanthera pedata, Cydonia oblonga, Cymbopogon martini, Cymbopogon nardus, Cymbopogon winterianus, Cynara cardunculus, Cyperus rotundus, Daucus carota, Dendranthema grandiflorum, Desmodium adscendens, Dimocarpus longan, Dioscorea oppostifolia, Dioscorea villosa, Diospyros kaki Thunb., Dunaliella saliena, Echinacea augustifolia, Echinacea pallida,Echinacea purpurea, Elaegnus rhamnoides, Alettaria cardamomum, Eleutherococcus senticosus, Elymus repens, Epiobium augustifolium, Epilobium parviflorum, Equisetum arvense, Erica cinerea, Erica tetralix, Eriobotrya japonica, Eriodictyon californicum, Erodium cicutarium, Eryngium campestre, Eschscholzia californica, Eucalyptus dives Schauer, Eucalyptus globulus, Eucalyptus radiata, Eucalyptus smithii F. Muell, Eucommia ulmoides, Eugenia uniflora, Eugenia jambolana, Euphrasia stricta D. Wolff, Euterpe oleracea, Fagopyrum esculentum Moench, Follopia japonica, Ferula assa-foetida, Ficus carica, Filipendula ulmaria, Foeniculum vulgare Mill., Forsythia suspensa, Fragaria dodonei Ard., Frangula purshiana Cooper, Fraxinus excelsior, Fraxinus ortus, Fucus serratus, Fucus vesiculosus, Fumaria officinalis, Galeopsis segetum Neck., Galium odotarum, Galium verum, Gardenia jasminoides J. Ellis, Gastrodia elata Blume, Gelidium corneum JV Lamouroux, Gentiana lutea, Geranium robertianum, Geum urbanum,Ginkgo biloba, Glycine max, Glycyrrhiza glabra, Glycyrrhiza uralensis, Gracilaria gracilis, Grindelia camporum Greene, Grindelia robusta Nutt., Grindelia squarrosa Dunal, Gymnema sylvestris, Haematococcus pluvialis, Hamamemis virginiana, Harpagophytum procumbens, Harpagophytum zeyheri Decne., Hedeoma pluegioides Pers., Helianthus annuus, Helienthus tuberosus, Helichrysum arenarium, Helichrysum stoechas, Herniara glabra, Hibiscus sabdariffa, Hieracium pilosella, Himanthalia elongata, Hordeum vulgare, Houttuynia cordata Thunb., Huperzia serrata, Hyssopus officinalis, Ilex paraguariensis A. St.-Hill, Illicum verum, Impatients balsamina, Inula britannica, Inula helenium, Jasminum grandiflorum, Jasmium officinale, Juniperus communis, Justicia adhatoda, Kavalama urens, Krameria lappacea, Lagerstroemia speciosa, Laminaria digitata, Laminaria hyperborea, Lamium album, Larix decidua, Larix occidentalis, Laurus nobilis, Lavandula augustofolia, Lavandula latifolia, Ledum palustre,Leonurus cardiaca, Lepidium meyenii Walp., Lepidium sativum, Lespedeza capitata, Levisticum officinale, Lindera aggregata, Linus usitatissimum, Liquidambar styraciflua, Lotus corniculatus, Lycium chinense, Lycium barbarum, Lycopersicon esculentum, Lycopodium clavatum, Lycopus europaeus, Lythrum salicaria, Macadamia ternifolia F. muell, Macrocystis pyrifera, Magnolia officinalis, Malpighia glabra, Malus pumila, Malus domestica, Malus sylvestris, Malva sylvestris, Mangifera indica, Maranta arundinacea, Marrubium vulgare, Marsdenia cundurango, Marsdenia sylvestris, Mastocarpus stellatus, Matricaria chamomilla, Medicago sativa, Melaleuca alternifolia, Melaleuca cajuputi Powell, Melaleuca leucadendra, Melaleuca quinquenrvia, Melaleuca viridiflora, Melilotus altissimus Thuill., Melilotus officinalis, Mentha arvensis, Mentha x piperita, Menyanthes trifoliata, Mesembryanthemum crystallinum, Monarda double, Morinda citrifolia, Morinda officinalis, White mulberry, Black mulberry, Murraya koenigii,Musa x paradisiaca, Myrciaria dubia, Myristica flagrans Houtt., Myroxylon balsamum, Myrtus communis, Nardostachys jatamansi, Nasturtium officinale R. Br., Nelumbo nucifera Gaertn., Nepeta cataria, Nepeta tenuifolia Benth., Nigella sativa, Ocimum basilicum, Oenothera biennis, Ononis spinosa, ophiopogon japonicus, Opuntia ficus-indica, Origanum compactum Benth., Origanum majorana, Origanum vulgare, Orthosiphon aristatus, Oryza sativa, Paeonia lactiflora, Paeonia x suffruticosa Andrews, Palmaria palmata, Panax ginseng, Panax quinquefolius, Panicum miliacium, Papaver rhoeas, Parietaria officinalis, Passiflora edulis Sims, Pastinaca sativa, Paullinia cupana Kunth, Pelargonium graveolens, Perilla frutescens, Persea americana, Persicaria bistorta, Persicaria maculosa Gray, Petroselinum crispum, Peucadanum ostruthium, Peumus boldus Molina, Phaseolus vulgaris, Phellodendron amurense, Photinia melancarpa, Phyllanthus emblica, Physalis alkekengi, Phymatolithon calcareum, Picea abies,Allspice, Allspice racemosa, Pimpinella anisum, Pimpinella major, Pimpinella saxfraga, Pinus mugo Turra, Pinus pinaster Aiton, Pinus sylvestris, Pistacia lentiscus, Plantago arenaria, Plantago lanceolata, Plantago major, Plantago ovata, Platycodon grandiflorus, Plectranthus barbatus Andrews, Pogostemom cablin, Polygala senega, Polygala sibirica, Polygala tenuifolia Willd., Polygonum aviculare, Populus nigra, Populus tremula, Populus tremuloides, Porphyra umbilicalis, Portulaca oleracea, Potentilla erecta, Primula veris, Prunella vulgaris, Prunus africana, Prunus armeniaca, Ribes nigrum, Ribes uva-crispa, Rosa canina, Rosa gallica, Rosa moschata, Rosa rubiginosa, Rosmarinus officinalis, Rubus caesius, Rubus fruticosus, Rubus idaeus, Rumex actetosa, Rumex acetosella, Rumex crispus, Rumex patienta, Ruscus aculeatus, Saccharina japonica, Saccharina latissima, Salix alba, Salix fragilis, Salix pentandra, Salix purpurea, Salvia officinalis L.,Salvia officinalis subsp. lavandulifolia Gams, Salvia sclarea, Sambucus nigra, Sanguisorba officinalis, Sanicula elata Buch.-Ham. Ex D. Don, Santalum album, Santolina chamaecyparissus, Saposhnikovia divaricata, Sargassum fusiforme, Satureja hortensis, Satureja montana, Saussurea costus, Scrophularia ningpoensis Helmsl., Scutellaria baicalensis Georgi, Secale cereale, Sedum acre, Sedum roseum, Senna alexandrina Mill., Senna obustifolia, Smilax cordifolia Humb., & Bonpl., Smilax glabra Roxb., Smilax officinalis Kunth, Smilax purhampuy Ruiz, Smilax purhampuy Ruiz, Smilax regelli Killip et CV Morton, Smilax vanillidora Apt, Solanum melongena, Solanum tuberosum, Solidago virgaurea, Sorbus aucuparia, Spatholobus suberctus Dunn., Spinacia oleracea, Spirulina major Kützing, Spirulina maxima Geitler, Spirulina platensis Geitler, Stavhys officinalis, Stemmacantha carthamoides Dittrich, Stypholobium japonicum, Syzgium aromaticum, Tagetes erecta, Tamarindus indica, Tanacetum parthemium, Terminalia chebula Retz., Theobroma cacao, Thymus saturejoides Coss., Thymus serpyllum, Thymus vulgaris, Thymus zygis, Tilia cordata Mill., Tilia platyphyllos Scop., Tilia tomentosa Moench, Tilia euopaea, Tribulus terrestris, Trichosanthes kirilowii Maxim., Trifolium arvense, Trifolium campestre Schreb., Trifolium pratense, Trifolium repens, Trigonella caerulea, Trigonella foenum-graecum, Tricitum aestivum, Tricitum durum Desf., Tricitum spelta L., Tricitum turgidum, Tropaeolum majus, Turnera diffusa Willd., Ulmus glabra Huds., Ulmus glabra Huds., Ulmus pumila, Ulmus rubra Muhl., Ulva lactuca, Uncaria gambir Roxb., Uncaria rhynchophylla Miq., Uncaria tomentosa DC., Undaria pinnatifida Suringar, Urtica dioca, Urtica urens, Vaccinium macrocarpon, Vaccinium oxycoccos, Vaccinium vitis-idae, Valeriana jatamansi Jones, Valeriana officinalis, Vanilla planifolia Jacks, Verbascum densiflorum Bertol., Verbascum thapsus, Verbena officinalis, Veronica officinalis, Viburnum opulus, Vigna angularis Ohwi & H. Ohashi, Vinca major, Vinca minor, Viola palustris, Viola tricolor, Vitex agnus-castus, Vitex trifolia, Vitis vinifera, Zea mays, Zingiber officinale Roscoe, Ziziphus jujuba Mill.

[0065] The compositions according to the invention can be in any form, in particular in powder, gel, emulsion or liquid form, especially in tablet, capsule, gel, stick, sachet, ampoule, dropper or injectable form.

[0066] The compositions according to the invention can be used as nutritional products or health products, in particular as medicines.

[0067] Nutritional products are defined as all products having a nutritional and / or physiological effect, including, in particular, food supplements, foods, dietetic products, etc. These products are administered orally, gastrically, or intravenously.

[0068] A health product is defined as any product that has a beneficial effect on health, whether for prevention or treatment, and whether that effect is physiological or pharmacological, including medications and pharmaceuticals. These products are typically administered orally, via the stomach, intravenously, or topically.

[0069] The compositions according to the invention can be used to prevent and / or combat disorders of carbohydrate and / or lipid metabolism in humans or animals.

[0070] They are particularly well-suited for preventing and / or managing type 2 diabetes in humans and animals. Indeed, they help prevent the development of chronic hyperglycemia, reduce fasting blood glucose and glycated hemoglobin, circulating and hepatic triglycerides, body mass and fat mass, increase HDL cholesterol ("good cholesterol"), and improve tolerance to ingested carbohydrates and insulin sensitivity. They can be used preventively during the treatment of type 2 diabetes and as a first-line treatment when initiating MHD (moderate-dose diabetes), thus delaying the introduction of standard oral antidiabetic medications. They are also particularly well-suited for the treatment of type 2 diabetes and its complications, notably non-alcoholic steatohepatitis (NASH), alone or in combination with other pharmacological treatments.

[0071] The compositions according to the invention can also be used in the prevention and / or control of type 1 diabetes and / or non-alcoholic fatty liver diseases, in particular non-alcoholic steatohepatitis (NASH), and / or cardiovascular diseases, in particular coronary heart disease, cerebrovascular diseases, peripheral arteriopathies, deep vein thrombosis, and / or diseases related to insulin resistance such as Alzheimer's disease (Bedse G et al. Front Neurosci 2015; 9:204).

[0072] For such uses, the compositions according to the invention can be used in combination with at least one antidiabetic therapeutic agent selected from among biguanides including metformin, dipeptidyl peptidase-IV (DPP-IV) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, thiazolidinediones (TZDs), sulfonylureas, rapid and long-acting insulins, glycosidase inhibitors (acarbose, miglitol, voglibose), sodium glucose co-transporter-2 (SGLT2) inhibitors, molecules of the fibranor family such as elafibranor, or molecules targeting nuclear receptors and in particular RORs (α, β, γ) and Rev-Erbs (α, β) receptors.

[0073] The compositions according to the invention can also be used to act on other cardiovascular risk factors or metabolic syndrome.

[0074] In particular, the compositions according to the invention can be used to prevent and / or treat dyslipidemia. They exhibit a cholesterol-lowering effect and reduce total cholesterol, LDL cholesterol, circulating triglycerides, and hepatic triglycerides. They also exhibit HMG-CoA reductase inhibitory activity.

[0075] For such uses, the compositions according to the invention can be used in combination with a hypolipidemic therapeutic agent selected from: statins, fibrates, nicotinic acid, ion exchange resins, cholesterol absorption inhibitors, omega-3 polyunsaturated fatty acids, tiadenol, and FXR (Farnesoid X Receptor) nuclear receptor agonists.

[0076] Finally, the compositions according to the invention can be used specifically to prevent or combat obesity and overweight and / or metabolic syndrome and / or pathological blood pressure problems.

[0077] The invention is now illustrated by examples of extracts and compositions, as well as by test results demonstrating the effectiveness of the compositions according to the invention, these examples and tests not being limiting. I. EXAMPLES Example 1: Example of a dry extract of Chrysanthellum indicum

[0078] The aerial parts of the plant, fresh or dried, are mechanically ground into a coarse powder. This powder is then macerated for 10 to 24 hours at room temperature in a 70 / 10 water / ethanol mixture. The resulting mixture is then continuously leached at 50°C in a percolator with a 70 / 10 water / ethanol mixture, at a plant-to-extract ratio of 3:1. The extract is then washed liquid-liquid with a non-polar organic solvent such as di- or trichloromethane. After concentration by low-pressure evaporation at 35°C, a liquid is obtained which, when freeze-dried for 24 hours, yields a beige powder soluble in a water / alcohol mixture. This powder (dry extract) can be used directly or mixed with a suitable solvent before use. Example 2: Example of a dry extract of Vaccinium myrtillus

[0079] Blueberry powder obtained from fruit Vaccinium myrtillus, The plant material is macerated for 10 to 24 hours at room temperature in a 30 / 50 water / ethanol mixture. The resulting mixture is then continuously leached at 50°C in a percolator with a 30 / 50 water / ethanol mixture, with a plant / extract ratio of 10:1. The extract is then washed liquid-liquid with a non-polar organic solvent such as di- or trichloromethane. After concentration by low-pressure evaporation at 35°C, a liquid is obtained which, when freeze-dried for 24 hours, yields a purple powder soluble in a water / alcohol mixture. Example 3: Example of a dry extract of Cynara scolymus

[0080] Artichoke in powder form obtained from leaves of Cynara scolymusThe plant material is macerated for 10 to 24 hours at room temperature in water. The resulting mixture is then continuously leached at 50°C in a percolator with water, using a plant-to-extract ratio of 2:1. The extract is then washed liquid-liquid with a non-polar organic solvent such as di- or trichloromethane. After concentration by low-pressure evaporation at 35°C, a liquid is obtained which, when freeze-dried for 24 hours, yields a water-soluble beige powder. Example 4: Example of a dry extract of Olea europaea

[0081] Whole, air-dried olive leaves are ground at -80°C using a knife mill to obtain a fine, homogeneous powder. This powder is then macerated for 10 to 24 hours in a 70 / 30 water / ethanol mixture. The maceration is carried out in a closed system with nitrogen bubbling at room temperature, or under 800 watts of microwave power, or at a 20 kHz ultrasonic frequency for 2 x 3 minutes. The resulting mixture is then continuously leached at 50°C in a percolator with a 70 / 30 water / ethanol mixture, at a plant-to-extract ratio of 10:1. The extract is then subjected to liquid-liquid washes using a non-polar organic solvent such as di- or trichloromethane. After concentration by evaporation at low pressure at 35°C, a liquid is obtained which, when freeze-dried for 24 hours, gives a green colored powder in a water / alcohol mixture. Example 6: example of a composition according to the invention in the form of tablets, comprising four plant extracts

[0082] The composition of Example 6 is presented in the form of orally administered tablets. It comprises, expressed as a percentage by weight relative to the total weight of the composition, 30.1% dry extract of aerial parts of Chrysanthellum indicum, 30.1% dry extract of leaves Cynara scolymus, 3.0% dry fruit extract Vaccinium myrtillus and 0.3% dry fruit extract Black pepper. It also includes excipients, in particular microcrystalline cellulose and magnesium stearate.

[0083] The composition for 3 tablets is indicated in the Table 1 following. Table 1. Example of composition in the form of tablets List of ingredients For 3 tablets Dry extract of aerial parts of Chrysanthellum indicum 600 mg Dry extract of leaves Cynara scolymus 600 mg Dry extract of fruit Vaccinium myrtillus 60 mg Dry extract of fruit Black pepper 6 mg Microcrystalline cellulose 700 mg Magnesium stearate 26 mg Example 7: example of a composition according to the invention in the form of capsules, comprising five plant extracts

[0084] The composition of Example 7 is presented in the form of orally administered capsules. It comprises, expressed as a percentage by weight relative to the total weight of the composition, 37.0% dry extract of aerial parts of Chrysanthellum indicum, 37.0% dry extract of leaves Cynara scolymus, 3.7% dry fruit extract Vaccinium myrtillus, 0.004% dry fruit extract Black pepper, and 22.2% dry extract of leaves of Olea europaea.

[0085] The composition for 3 capsules is indicated in the Table 2 following. Table 2. Example of composition in capsule form List of ingredients Per 3 capsules Dry extract of aerial parts of Chrysanthellum indicum 200 mg Dry extract of leaves Cynara scolymus 200 mg Dry extract of fruit Vaccinium myrtillus 20 mg Dry extract of fruit Piper nigrum 0.02 mg Dry extract of leaves of Olea europaea 120 mg Example 8: Example of a composition according to the invention in tablet form, comprising five plant extracts

[0086] The composition of Example 8 is presented in the form of orally administered tablets. It comprises, expressed as a percentage by weight relative to the total weight of the composition, 22.0% dry extract of aerial parts of Chrysanthellum indicum,22.0% dry extract of leaves Cynara scolymus, 2.2% dry fruit extract Vaccinium myrtillus, 13.2% dry extract of leaves of Olea europaea, and 0.2% dry fruit extract Piper nigrum. The composition also includes, in addition to the zinc mixture, vitamins B9, PP, B5, H, B12, D, B6, B2, and chromium. It also contains excipients, notably dicalcium phosphate, microcrystalline cellulose, and magnesium stearate.

[0087] The composition for 1 tablet is indicated in the Table 3 following. Table 3. Example of composition in tablet form List of ingredients In mg per tablet Reference Intake per tablet Dry extract of aerial parts of Chrysanthellum indicum 220,0 - Dry extract of leaves Cynara scolymus 220,0 - Dry extract of fruit Vaccinium myrtillus 22,0 - Dry extract of leaves of Olea europaea 132,0 - Dry extract of fruit Piper nigrum 2,0 - Dicalcium phosphate 198,0 - Microcrystalline cellulose 153,44 - Magnesium stearate 20,0 - Zinc bisglycinate 12,99 33% Vitamin B9 - folic acid 7,30 33% Vitamin PP - nicotinamide 5,30 33,1% Vitamin B5 - calcium pantothenate 2,24 33,3 Vitamin H - biotin 1,66 33,2% Vitamin B12 0,83 33,2% Vitamin D3 0,64 32% Vitamin B6 - pyridoxine hydrochloride 0,56 32,9% Vitamin B1 - Thiamine Hydrochloride 0,48 32,7% Vitamin B2 - riboflavin 0,45 32,1% Chromium picolinate 0,11 32,5% Example 9: Example of a composition according to the invention in tablet form, comprising four plant extracts

[0088] The composition of Example 9 is presented in the form of orally administered tablets. It comprises, expressed as a percentage by weight relative to the total weight of the composition, 23.9% dry extract of whole plants of Chrysanthellum indicum, 23.9% dry extract of leaves Cynara scolymus, 23.9% dry fruit extract Vaccinium myrtillus and 0.2% dry fruit extract Piper nigrum. The formula also contains vitamin B1, vitamin B3, pantothenic acid (vitamin B5), zinc, and chromium. Excipients include microcrystalline cellulose and dicalcium phosphate. Coating agents include talc, sugar, shellac, povidone, and beeswax.

[0089] The composition for 3 tablets is indicated in the Table 4 following. Table 4. Example of tablet composition List of ingredients For 3 tablets Reference Intake per 3 tablets Dry extract of fruit Vaccinium myrtillus 600 mg - Dry extract of whole plants Chrysanthellum indicum 600 mg - Dry extract of leaves Cynara scolymus 600 mg - Dry extract of fruit Piper nigrum 5 mg - Vitamin B1 1.1 mg 100% Vitamin B3 (inositol hexanicotinate) 16 mg (nicotinic acid) 100% Pantothenic acid (vitamin B5) 6 mg 100% Zinc (zinc bisglycinate) 5 mg 50% Chromium (chromium picolinate) 40 µg 100% Microcrystalline cellulose 600 mg - Dicalcium phosphate 75 mg - Example 10: Example of a composition according to the invention in the form of a powder to be reconstituted in water, packaged in stick form, comprising four plant extracts

[0090] Example 10's composition is presented as a powder to be reconstituted with water, packaged in orally administered sticks. It comprises, expressed as a percentage by weight relative to the total weight of the composition, 36.3% dry extract of whole plants of Chrysanthellum indicum, 24.2% dry extract of roots of Cynara scolymus, 36.3% dry fruit extract Vaccinium myrtillus and 2.4% dry fruit extract Piper longum. The formula also contains vitamin B1, vitamin B3, pantothenic acid (vitamin B5), zinc, and chromium. It provides natural blueberry flavoring. Malic acid is used as an acidifier. Silicon dioxide acts as an anti-caking agent, xanthan gum as a thickener, and calcium phosphate as a stabilizer.

[0091] Its composition is indicated in the Table 5 following. Table 5. Example of a powder composition to be reconstituted in water and packaged in stick form List of ingredients For 3 sticks Reference Intake per 3 sticks Dry extract of fruit Vaccinium myrtillus 1500 mg - Dry extract of whole plants Chrysanthellum indicum 1500 mg - Dry extract of roots of Cynara scolymus 1000 mg - Dry extract of fruit Piper longum 100 mg - Vitamin B1 1.1 mg 100% Vitamin B3 (inositol hexanicotinate) 16 mg (nicotinic acid) 100% Pantothenic acid (vitamin B5) 6 mg 100% Zinc (zinc bisglycinate) 5 mg 50% Chromium (chromium picolinate) 40 µg 100% Example 11: Example of a composition according to the invention in the form of a powder to be reconstituted in water, packaged in stick form

[0092] The composition of Example 11 is presented as a powder to be reconstituted in water, packaged in sticks for oral administration. It comprises, expressed as a percentage by weight relative to the total weight of the composition, 37.0% dry extract of aerial parts of Chrysanthellum indicum, 37.0% dry extract of leaves Cynara scolymus, 3.7% dry fruit extract Vaccinium myrtillus, 0.2% dry fruit extract Piper nigrum, and 22.2% dry extract of leaves of Olea europaea.The formula also includes vitamin B12 and chromium. It contains natural strawberry flavoring. Silicon dioxide is used as an anti-caking agent. This formula does not contain any other anti-caking agents or thickeners.

[0093] The composition of such a product is indicated in the Table 6 following. Table 6. Example of a powder composition to be reconstituted in water and packaged in stick form List of ingredients For 3 sticks Reference Intake per 3 sticks Dry extract of fruit Vaccinium myrtillus 120 mg - Dry extract of aerial parts of Chrysanthellum indicum 1200 mg - Dry extract of leaves Cynara scolymus 1200 mg - Dry extract of fruit Piper nigrum 6 mg - Dry extract of leaves of Olea europaea 720 mg - Vitamin B3 (inositol hexanicotinate) 2,5 µg 100% Chromium (chromium picolinate) 20 µg 50% Example 12: Example of a composition according to the invention in capsule form

[0094] The composition of Example 12 is presented in the form of orally administered capsules. It comprises, expressed as a percentage by weight relative to the total weight of the composition, 31.6% dry extract of aerial parts of Chrysanthellum indicum, 47.4% dry extract of roots of Cynara scolymus, 15.8% dry fruit extract Vaccinium myrtillusand 2.6% piperine. The composition also includes vitamin B3 and zinc. As an emulsifier, it contains non-GMO soy lecithin; as thickeners, colloidal silica and mono- and diglycerides of fatty acids. The capsule is made of fish gelatin, with glycerin and a colorant, red iron oxide.

[0095] The composition of such a product is indicated in the Table 7 following. Table 7. Example of composition in capsule form List of ingredients Per 2 capsules Reference Intake per 2 capsules Dry extract of fruit Vaccinium myrtillus 100 mg - Dry extract of aerial parts of Chrysanthellum indicum 200 mg - Dry extract of roots of Cynara scolymus 300 mg - Piperine 15 mg - Vitamin B3 8 mg (nicotinic acid) 50% Zinc (zinc gluconate) 10mg 100% Example 13: Example of a composition according to the invention in capsule form

[0096] The composition of Example 13 is presented in the form of orally administered capsules. It comprises, expressed as a percentage by weight relative to the total weight of the composition, 10.4% dry extract of whole plants of Chrysanthellum Indicum, 20.7% dry extract of leaves of Cynara scolymus,62.1% dry extract of leaves Vaccinium myrtillus and 2.6% piperine. It contains corn starch as a bulking agent. Silicon dioxide and magnesium stearate are used as anti-caking agents. The capsule is of vegetable origin.

[0097] The composition of such a product is indicated in the Table 8 following. Table 8. Example of composition in capsule form List of ingredients Per capsule Reference Intake per 1 capsule Dry extract of leaves Vaccinium myrtillus 300 mg - Dry extract of whole plants Chrysanthellum indicum 50 mg - Dry extract of leaves Cynara scolymus 100 mg - Piperine 15 mg - Example 15: Examples of compositions according to the invention in tablet form comprising synthetic molecules or molecules obtained from plant-based raw materials

[0098] Example 15 is presented as film-coated tablets for oral administration. The active ingredients per tablet are: 50 mg apigenin-7-O-glucuronide, 50 mg dicaffeoylquinic acid, 100 mg monocafeoylquinic acid, 10 mg piperine, and 250 mg oleuropein. The other ingredients used as excipients are: pregelatinized starch, sodium starch glycolate (type A), stearic acid, povidone K90, and colloidal anhydrous silica.

[0099] The active substances can be synthetic or derived from plant raw materials or from plant extracts by purification by high-performance liquid chromatography. II. IN VIVO EVALUATION OF THE EFFECTIVENESS OF THE COMPOSITION

[0100] Experiments in vivoStudies on mice were conducted to demonstrate the effects of the compositions according to the invention, particularly on fasting blood glucose, glycated hemoglobin, glucose tolerance, insulin sensitivity, body mass and fat mass, and circulating and hepatic lipids. Similarly, molecular biology assessments were performed. Finally, the compositions were compared to reference pharmacological treatments already on the market or under development.

[0101] The experiments were conducted on db / db mice. These mice have a mutation in their leptin receptors, leading to dysregulation of leptin cell signaling. Leptin receptors are highly expressed in the hypothalamus. Mice with this receptor mutation cannot effectively regulate their energy stores. This results in elevated insulin levels from the first days of life (10-14 days) and obesity starting at 3-4 weeks, accompanied by elevated blood glucose levels. These mice are insulin resistant, hypertriglyceridemic, and glucose intolerant. They constitute a relevant and predictive model, particularly for the study of insulin sensitivity, triglyceridemia, type 2 diabetes and one of its complications, non-alcoholic fatty liver disease (NASH) (Aileen JF King Br J Pharmacol 2012; 166(3):877-894; Sanches SC et al. Biomed Res Int 2015). II.1 Trials A

[0102] The experimental time was 9 weeks with a 1-week "Run-in" followed by 8 weeks of supplementation with plant extracts and composition X. Male mice were 10 weeks old at the start of treatment.

[0103] Nine X compositions were tested. These compositions were directly incorporated into the rodents' diet, ensuring their multi-target efficacy and large-scale use, as intravenous or intraperitoneal injections are limited to a small number of individuals due to their method of administration. This also avoids daily force-feeding, which disrupts various physiological processes.

[0104] The compositions tested were as follows: ▪ C1: Chrysanthellum indicum (whole plant) + piperine (1% and 0.1% of the diet, respectively); ▪ C2: Cynara scolymus(leaves) + piperine (1% and 0.1% of the diet, respectively); ▪ C3: Vaccinium myrtillus (fruits) + piperine (1% and 0.1% of the diet, respectively); ▪ C4: Chrysanthellum indicum (whole plant) + Cynara scolymus (leaves) + Vaccinium myrtillus (fruits) + piperine (respectively 1%, 1%, 1% and 0.1% of the diet); ▪ C5: piperine (0.1% of the diet); ▪ C6: Chrysanthellum indicum (whole plant) + Cynara scolymus (leaves) + Vaccinium myrtillus (fruits) (respectively 1%, 1% and 1% of the diet); ▪ C7: Chrysanthellum indicum (whole plant) + Cynara scolymus (leaves) + Vaccinium myrtillus (fruits) + piperine (respectively 1%, 1%, 1%, 0.001% of the diet); ▪ C8: Olea europaea (leaves) (0.6% of the diet); ▪ C9: Chrysanthellum indicum (whole plant) + Cynara scolymus (leaves) + Vaccinium myrtillus (fruits) + piperine + Olea europaea (leaves) (respectively 1%, 1%, 1%, 0.001%, 0.6% of the diet).

[0105] Piperine refers either to synthetic piperine or to an extract of Piper standardized to 95% piperine. For the other plants, these were dry extracts obtained from plant raw materials.

[0106] The experiments took place in several stages. Consequently, several "Control" groups ad libitum were carried out. The results from these groups were pooled. Compositions C1, C2, C3, C4, C5, C8, and C9 induced a similar decrease in food intake. Therefore, a "Control" group Per Fed ", i.e. consuming the same daily amount of food as groups C1, C2, C3, C4, C5, C8 and C9, was carried out in such a way as to be able to compare the results with equivalent food intake.

[0107] The experimental evaluations focused in particular on: Body mass measurement; fasting blood glucose measurement; and blood glucose response during an oral carbohydrate tolerance test. After fasting starch gavage (3 g / kg), blood glucose response to starch was measured by tail biopsy just before gavage (t0), and then after 30, 60, 90, and 120 minutes. The area under the curve (AUC) was calculated. An increased AUC indicates carbohydrate intolerance, while a decreased AUC indicates improved carbohydrate tolerance.

[0108] For compositions C7 to C9, an insulin sensitivity test was also performed. This test consisted of an intraperitoneal injection of insulin (2 U / kg) in the fasting state. The change in blood glucose levels in response to the insulin injection was measured at the tail end by biopsy just before the injection (t0), and then after 30, 60, 90, and 120 minutes. The area under the curve (AUC) was calculated. A decrease in the AUC indicates a better response to the insulin injection and therefore improved insulin sensitivity. Conversely, an increase in the AUC indicates poorer insulin sensitivity and therefore insulin resistance.

[0109] The assessments presented were carried out just before supplementation (t = 0) and at the end of supplementation (t = 8 weeks).

[0110] The results obtained are presented in tables: Table 9regarding the effect on insulin sensitivity after 8 weeks of treatment, Table 10 Regarding the effect on fasting blood glucose after 8 weeks of treatment, Table 11 Regarding the effect on carbohydrate tolerance after 8 weeks of treatment, Table 12 for the effect on body mass after 8 weeks of treatment. Insulin sensitivity

[0111] Table 9. Effect of compositions on insulin sensitivity after 8 weeks of treatment Compositions AUC (week 8 - week 0, in mg / min / dL) (mean ± SEM) Control at will 19 186 ± 3460 C7 2082 ± 2082 ** C8 8970 ± 2959 C9 -6520 ± 4685 ** Average values ​​± SEM. Control ad libitum, n = 20; C7, n = 11; C8, n = 10; C9, n = 9. Composition versus Control, Test t Student's t-value for unpaired data, ** p < 0.01.

[0112] The results presented in the Table 9 are also illustrated on the Figure 1These results demonstrate a highly significant and important effect of the C7 and C9 compositions on insulin sensitivity. The improvement in insulin sensitivity with the C7 and C9 compositions according to the invention is particularly relevant for the prevention and treatment of type 2 diabetes and its complications. Indeed, insulin resistance is one of the major mechanisms of progression in type 2 diabetes (Samuel VT et al. Cell 2012; 148:852-71). Furthermore, by acting on this parameter, the C7 and C9 compositions according to the invention are particularly well-suited for other conditions in which insulin resistance is a significant contributing factor. This is particularly the case with one of the complications of type 2 diabetes, non-alcoholic fatty liver disease (NASH; Samuel VT et al. Cell 2012; 148:852-71), and with Alzheimer's disease (Bedse G et al. Front Neurosci 2015; 9:204). Fasting blood glucose

[0113] Table 10. Effect of the compositions on fasting blood glucose after 8 weeks of treatment Compositions Fasting blood glucose (in mg / dL) Control at will 534 ± 10 Control Per Fed 518,2 ± 38 C1 410,4 ± 33 * C2 448 ± 34 C3 384 ± 40* C4 335 ± 38** C5 449 ± 11 C6 536 ± 15 C7 571 ± 14 * C8 400 ± 61 C9 220 ± 78 ** Average values ​​± SEM. Control ad libitum, n = 32; Control Per Fed, n = 10; C1, n = 9; C2, n = 9; C3, n = 9; C4, n = 8; C5, n = 9; C6, n = 14; C7, n = 12; C8, n = 12; C9, n = 9. Composition versus Control, Test t Student's t-test for unpaired data, * p < 0.05, ** p < 0.01.

[0114] Compositions C1, C2, C3, C4, C5, C8, and C9 caused a decrease in food intake. Therefore, a group Per Fed consuming the same amount of food was carried out. The results show that the caloric restriction imposed on the animals had no effect on fasting blood glucose (comparison with ad libitum control). versus Per Fed control). Compositions C1, C3, C4, and C9 induced a significant decrease in fasting blood glucose, with the most pronounced effect observed with composition C4 ( Chrysanthellum indicum 1%, Cynara scolymus 1%, Vaccinium myrtillus 1%, piperine 0.1%) and C9 ( Chrysanthellum indicum 1%, Cynara scolymus 1%, Vaccinium myrtillus 1%, piperine 0.001%, Olea europaea 0.6%).

[0115] Composition C6 ( Chrysanthellum indicum 1%, Cynara scolymus 1%, Vaccinium myrtillus1%) had no effect on fasting blood glucose. The addition of piperine (0.1%), even though it (C5) did not induce a significant decrease in fasting blood glucose, to the C6 combination to obtain the C4 combination, surprisingly resulted in a significant and substantial decrease in fasting blood glucose. Similarly, the addition of Olea europaea (0.6%; C8) to the combination C7 ( Chrysanthellum indicum 1%, Cynara scolymus 1%, Vaccinium myrtillus 1%, piperine 0.001%) to obtain the C9 composition also made it possible to significantly lower blood glucose to a level almost similar to that of non-diabetic mice. Carbohydrate tolerance

[0116] Table 11. Effect of compositions on carbohydrate tolerance after 8 weeks of treatment Compositions AUC (week 8 - week 0, in mg×min / dL) (mean ± SEM) Control at will 10 954 ± 2000 Control Per Fed 20 355 ± 6554 C1 3367 ± 3039 * C2 1901 ± 3949 * C3 -2418 ± 3260 ** C4 -11 537 ± 4168 ** C5 3610 ± 2086 * C6 13 068 ± 3064 C7 8639 ± 2844 C8 -8889 ± 5436 ** C9 -24 568 ± 10 440 ** Average values ​​± SEM. Control ad libitum, n = 22; Control Per Fed, n = 10; C1, n = 9; C2, n = 8; C3, n = 10; C4, n = 8; C5, n = 9; C6, n = 14; C7, n = 12; C8, n = 10; C9, n = 9. AUC: “aera under the curve”. Composition versus Control, Test t Student's t-test for unpaired data, * p < 0.05, ** p < 0.01.

[0117] Compositions C1, C2, C3, C4, C5, C8, and C9 caused a decrease in food intake. Therefore, a group Per Fed consuming the same amount of food was carried out. The results show that the caloric restriction imposed on the animals had no effect on carbohydrate tolerance (comparison with ad libitum control). versus Per Fed control). Compositions C1, C2, C3, C4, C5, C8, and C9 induced a significant decrease in AUC, reflecting improved carbohydrate tolerance. The most pronounced effect was observed with the C4 and C9 combinations. Body mass

[0118] Table 12. Effect of compositions on body mass after 8 weeks Compositions Body mass (in g, average ± SEM) Control at will 36,9 ± 1,2 Control Per Fed 30,6 ± 1,2 C1 33,9 ± 2,4 C2 37,4 ± 2,2 * C3 37,0 ± 2,7 * C4 36,3 ± 1,7 * C5 32,7 ± 1,5 C6 29,3 ± 1,8 *** C7 34,5 ± 1,6 C8 26,9 ± 2,0 C9 25,0 ± 2,1 * Average values ​​± SEM. Control ad libitum, n = 34; Control Per Fed, n = 10; C1, n = 9; C2, n = 9; C3, n = 9; C4, n = 8; C5, n = 9; C6, n = 14; C7, n = 12; C8, n = 10; C9, n = 9. Composition versus Control, Test t Student's t-test for unpaired data, * p < 0.05, ** p < 0.01, *** p < 0.0001.

[0119] Compositions C1, C2, C3, C4, C5, C8, and C9 caused a decrease in food intake. Therefore, a group Per Fed consuming the same amount of food was carried out. The results show that the caloric restriction imposed on the animals induced a significant decrease in body mass (comparison with an ad libitum control). versus Per Fed control, p < 0.05). Compositions C2, C3, C4, C6, and C9 also induced a significant decrease in body mass. While combination C6 had no effect on fasting blood glucose, it induced a substantial and significant decrease in body mass, giving it interesting properties in the prevention and treatment of obesity. Combination C9 had the most pronounced effect. Synergistic effect

[0120] Furthermore, the synergistic effect was evaluated using the Colby SR method described in "Calculation of the synergistic and antagonistic responses of herbicide combinations," Weeds, 1967, 15:20-22. This method was notably used in patent EP03812880. For each combination, the synergy factor was calculated. A factor > 1 indicates the existence of a synergistic effect. A factor < 1 indicates the existence of an antagonist. The calculations performed are: Taux d ′ efficacité attendu = A + B − A * B / 100 Facteur de synergie FS = 1 * taux d'efficacité observé % / taux d ′ efficacité attendu %

[0121] The calculations were based on the following combinations: Calculation of FS for the Chrysanthellum indicum 1% combination / Cynara scolymus 1% / Vaccinium myrtillus 1% / piperine 0.1% (composition C4) where A = Chrysanthellum indicum 1% / Cynara scolymus 1% / Vaccinium myrtillus 1% (C6) and B = piperine (C5) ; Calculation of FS for the Chrysanthellum indicum 1% combination / Cynara scolymus 1% / Vaccinium myrtillus 1% / piperine 0.001% / Olea europaea 0.6% (composition C9) where A = Chrysanthellum indicum 1% / Cynara scolymus 1% / Vaccinium myrtillus 1% / piperine 0.001% (composition C7) and B = Olea europaea 0.6% (composition C8).

[0122] THE Table 13 The following gives the results for the combination C6 + C5 = C4. Table 13. Synergy factors for the combination C6 + C5 = C4 Observed efficacy rate (as a percentage of the control group) Expected efficiency rate with C4 Synergy factor C6 C5 C4 Fasting blood glucose after 8 weeks of treatment +2,6% -13,3% -35,3% -11,0% 3,20 Oral carbohydrate tolerance test, AUC (week 8 - week 0) +9,5% -82,3% -156,7% -82,3% 1,94

[0123] The results presented in the Table 13 are illustrated on the Figures 2 And 3 . A significant synergistic effect with the C4 composition according to the invention is demonstrated, both on fasting blood glucose and on carbohydrate tolerance (AUC).

[0124] THE Table 14 The following gives the results for the combination C7 + C8 = C9. Table 14. Synergy factors for the combination C7 + C8 = C9 Observed efficacy rate (as a percentage of the control group) Expected efficiency rate with C9 Synergy factor C7 C8 C9 Fasting blood glucose after 8 weeks of treatment +5,7% -26,1% -59,4% -21,9% 2,71 Oral carbohydrate tolerance test, AUC (week 8 - week 0) +4,6% -204,5% -388,7% -209,3% 1,86 Oral insulin sensitivity test, AUC (week 8 - week 0) -89,1% -53,2% -129,3% -94,9% 1,36

[0125] The results presented in the Table 14 are illustrated in the Figures 4 , 5 and 6A significant synergistic effect with composition C9 according to the invention is demonstrated, both on fasting blood glucose, carbohydrate tolerance (AUC), and insulin sensitivity (AUC). This is despite the fact that composition C7 already had a significant and important effect on improving insulin sensitivity. 11.2 Tests B

[0126] Another composition, C10, was developed and tested. in vivo : Chrysanthellum indicum (aerial part, dry extract) + Cynara scolymus (leaves, dry extract) + Vaccinium myrtillus (fruits, dry extract) + Piper nigrum (fruits, dry extract) + Olea europaea (leaves, dry extract).

[0127] More specifically, the C10 composition was tested in vivocompared to metformin, the reference therapeutic molecule in the treatment of type 2 diabetes, using the same model as Trial A (db / db mice). Using this predictive diabetic mouse model and incorporating the C10 composition directly into the rodents' diet ( Chrysanthellum indicum 1%, Cynara scolymus 1%, Vaccinium myrtillus 0.1%, Piper nigrum 0.001% and Olea europaea 0.6% of the diet), this ensures its "multi-target" effectiveness and its large-scale use, intravenous or intraperitoneal injections being limited to a small number of people given their method of administration.

[0128] The experimental time was 7 weeks, with a 1-week run-in followed by 6 weeks of supplementation with the C10 composition. Male mice were 6 weeks old at the start of treatment. Assessments were performed just before supplementation (t = 0), weekly for certain parameters, and at the end of supplementation (t = 6 weeks).

[0129] The experimental evaluations focused in particular on: Measurement of food intake (t1, t2, t3, t4 and t5 weeks); Measurement of body mass (t0, t1, t2, t3, t4, t5, t6 weeks); Measurement of fat and lean mass by MRI (Magnetic Resonance Imaging; t0 and t6 weeks); Measurement of fasting blood glucose (t0, t1, t2, t3, t4, t5, t6 weeks); Measurement of glycated hemoglobin (HbA1c; t6 weeks); Insulin sensitivity (test identical to that performed in Trial A; t0 and t6 weeks); Carbohydrate tolerance (test identical to that performed in Trial A; t0 and t6 weeks); Measurement of serum and liver triglycerides (t6 weeks); Measurement of serum HDL cholesterol (t6 weeks).

[0130] All of these assessments are perfectly familiar to those in the profession.

[0131] The results are presented in the Table 15Next. It is important to consider that the amount of metformin ingested daily by the mice was approximately 26% greater than the total amount of molecules present in composition C10 according to the invention. In other words, the dose of metformin administered was greater than the total dose of molecules present in composition C10. Settings Control Metformin C10 Food intake (g / day) 9.6 ± 0.5 10.0 ± 0.6 10.7 ± 0.8 Body mass (g) 44.7 ± 2.0 40.8 ± 2.1 36.3 ± 1.7 a< Body fat (%) 26.1 ± 1.5 23.2 ± 1.7 19.1 ± 1.1 a< Lean mass (%) 17.0 ± 0.5 16.5 ± 0.5 16.5 ± 0.6 Fasting blood glucose (mg / dL) 437 ± 26 474 ± 24 160 ± 20 a,b< HbA1c (%) 8.33 ± 0.53 7.59 ± 0.24 4.25 ± 0.20 a,b< Area under the curve measured during an oral insulin sensitivity test (AUC, mg.min / dL) 50940 ± 2968 32778 ± 3166 14109 ± 1856 a,b< Area under the curve measured during an oral carbohydrate tolerance test (AUC, mg.min / dL) 61050 ± 2757 65614 ± 1577 28823 ± 5333 a,b< Serum triglycerides (mg / dL) 231.23 ± 18.29 256.23 ± 28.19 177.80 ± 19.60 b< Hepatic triglycerides (µmol / mg tissue) 41.10 ± 1.80 38.39 ± 4.84 21.39 ± 2.21 a,b< HDL cholesterol (mg / dL) 74.34 ± 4.10 99.21 ± 6.03 111.72 ± 8.39 a< Mean values ​​± SEM. Control, n = 10; Metformin, n = 11; C10, n = 10. Test t Student's t-test for unpaired data. a< : C10 versus Control, p < 0.05. b < : C10 versus Metformin, p < 0.05.

[0132] There Figure 7 illustrates more particularly the effects of metformin and the C12 composition according to the invention on insulin sensitivity.

[0133] The results illustrated in the Table 15demonstrate an extremely important and surprising effect of the C10 composition according to the invention on a range of risk factors for metabolic syndrome, overweight, obesity, diabetes, non-alcoholic fatty liver disease (NASH), and cardiovascular diseases, namely: ▪ Reduction of body weight through a decrease in fat mass, without affecting lean mass; ▪ A decrease in fasting blood glucose and glycated hemoglobin; ▪ An improvement in carbohydrate tolerance; ▪ An improvement in insulin sensitivity; ▪ A decrease in liver and serum triglycerides; ▪ An increase in HDL cholesterol ("good cholesterol").

[0134] Not only does the composition according to the invention reduce a whole range of risk factors, but it also improves them to a level almost equivalent to that of non-diabetic mice (healthy mice). In other words, the invention prevents the onset and progression of type 2 diabetes.

[0135] THE Figures 8 And 9 illustrate the effects of the C10 composition according to the invention on changes in body mass and fasting blood glucose compared to the control group. The C10 composition according to the invention significantly limits mass gain and prevents an increase in blood glucose.

[0136] Furthermore, its effects are far superior to those of metformin, the main antidiabetic drug (Ferrannini E et al. Eur Heart J 2015; Jun 10; example: GLUCOPHAGE®), and it demonstrates the absence of side effects on circulating lipids, unlike OCA (obeticholic acid, an FXR agonist for the treatment of type 2 diabetes and NASH (non-alcoholic steatohepatitis)) developed by INTERCEPT, which drastically reduces circulating HDL cholesterol (-0.2 g / L, p < 0.01) ("good cholesterol"). On the contrary, the composition according to the invention increases circulating HDL cholesterol levels by 50.3%.

[0137] Furthermore, the effect of the composition according to the invention is superior to that of the drug candidate developed by GENFIT, GFT 505 (Elafibranor), on glycated hemoglobin (HbAlc), the main diagnostic indicator of type 2 diabetes and its morbid complications: C10 composition, HbAlc = 4% versusGFT 505, HbA1c = 6% for the highest dose (same db / db mouse model and similar experimental design; Hanf R et al. Diab Vasc Dis Res 2014; 11:440-7). A further 1% reduction in HbA1c decreases the risk of myocardial infarction by 14%, cardiovascular disease by 37%, and amputation by 43%. Furthermore, the composition according to the invention delays, or even stops, the degeneration of pancreatic beta cells, the cells responsible for insulin secretion in response to increased blood glucose levels. Indeed, type 2 diabetes progressively induces the degradation of pancreatic beta cells, partly due to chronic hyperglycemia. This results in an increase in insulin secretion in the early stages of the disease to lower blood glucose (increased insulinemia), followed by a progressive decrease in its secretion (lower circulating insulinemia), due to the progressive destruction of Beta cells (Leahy JL et al.J Clin Invest 1985;77:908-915). The results obtained strongly support an effect of the C10 composition on pancreatic beta cells. Indeed, after six weeks of supplementation, insulin levels were higher in the group with the C10 composition according to the invention. versus Control (27.40 ± 4.11 versus 9.64 ± 2.53 ng / mL, p < 0.01, respectively), reflecting a very different stage of diabetes: advanced diabetes in the Control group with destruction of Beta cells (low insulin, high fasting blood glucose, high HbAlc) and early-stage or even no diabetes in the group of composition C10 according to the invention with functional Beta cells (high insulin, low blood glucose, low HbAlc).

[0138] Thus, the invention perfectly addresses the need for new preventative and therapeutic solutions that take into account the multifactorial nature of cardiometabolic disorders. This invention represents a major advancement in significantly curbing the development of metabolic diseases and their morbid impact.

[0139] Molecular biology measurements were also performed at the liver level. These assessments were conducted after six weeks of treatment and after animal sacrifice. In particular, hepatic AMPK (AMP-activated protein kinase) levels were determined by Western blot. AMPK is considered a metabolic sensor. A ubiquitous enzyme, AMPK participates in the coordinated regulation of energy metabolism, food intake, and tissue sensitivity in response to numerous metabolic and hormonal signals. These properties therefore make it a major pharmacological target for metabolic (diabetes, insulin resistance, obesity) and cardiological (cardiac ischemia, diabetic complications) conditions (Coughlan KA et al. Diabetes Metab Syndr Obes 2014;7:241-53).Increasing AMPK levels is a key strategy in identifying and validating treatments for type 2 diabetes and its complications (particularly non-alcoholic fatty liver disease), and more generally for pathologies related to metabolic disorders.

[0140] The results show at the hepatic level that the C10 composition according to the invention induces a net increase in the amount of AMPK (Control n = 9, 1.00 ± 0.22 versus C10 n = 9, 1.96 ± 0.73, p < 0.001, Mann-Whitney U test). The results are illustrated by the western blot. Figure 10 .

[0141] The experimental protocol, which can be carried out by any person skilled in the art, is indicated in the following lines. → AMPK Protein extraction

[0142] 50 mg of frozen tissue (liver) were placed in 20 volumes of NP-40 buffer (Tris HCl 50 mM, pH 7.4, NaCl 150 mM, NaF 1 mM, Na3VO4 1 mM, Nonidet P-40 1%, Sodium deoxycholate 0.25%) in the presence of 1 µL of protease inhibitor cocktail (P8340, Sigma Aldrich) and phosphatase inhibitor tablets (#88667 Thermo Fisher Scientific, USA). The tissues were homogenized on ice using a glass potter and then centrifuged at 14,000 g for 10 minutes at 4°C before collecting the supernatant. The protein content of the supernatant was measured using a Bio-Rad DC kit (Bio-Rad, USA) and then all samples were brought back to the same standard concentration before being diluted a second time in Laemmli 2X buffer and then heated to 90°C for 3 minutes. Blotting

[0143] For each assay, a molecular weight ladder and an internal control were loaded alongside 15 µg of each sample onto a polyacrylamide gradient gel (4-15% Mini-PROTEAN® TGX Stain-Free™ Gel, BioRad, USA). The gels were then subjected to a 300V current for 18 to 20 minutes in an electrophoresis buffer (Tris 25 mM, Glycine 192 mM, SDS 0.1%) before the proteins were transferred to a PVDF membrane using a semi-liquid transfer system (Transblot, Bio-Rad, USA) with a 25V, 2.5A DC current for 7 minutes. The membranes were then incubated in Tween-Tris saline buffer (TTBS: 50 mM Tris base pH 7.5, 150 mM NaCl, and 0.01% Tween 20) enriched with 5% BSA for 1 hour at room temperature. The membranes were then rinsed with TTBS and incubated overnight at 4°C with anti-AMPKα antibodies (D63G4, Cell Signaling, USA).After incubation, the membranes were washed again with TTBS and then exposed to a secondary anti-rabbit antibody conjugated to horseradish peroxidase at a concentration of 1:3000 for 1 hour at room temperature. The membranes were then washed three times in TTBS before being exposed to a chemiluminescence solution (Clarity Western ECL; Bio-Rad, USA) for 1 minute. The membranes were then scanned on a Bio-Rad Chemidoc system, and the intensity of the bands was measured using the provided image analysis software (ImageLab V4.1, Bio-Rad, USA). II.3 Test C

[0144] One of the main drawbacks of many therapeutic molecules currently on the market is their acute hypoglycemic effect, with a high risk of hypoglycemia. To test the acute hypoglycemic effect of the C10 composition according to the invention, the composition was administered by gavage (400 mg / kg) to six healthy C57BL / 6N mice. Blood glucose levels were measured by tail biopsy before and after gavage (t0, t15 minutes, t30 minutes). In addition, according to a crossover protocol, the same mice received a saline solution by gavage, with blood glucose measurements (t0, t15 minutes, t30 minutes). The results are illustrated in the Figure 11 demonstrates the absence of an acute hypoglycemic effect of the C10 composition according to the invention. III. IN VITRO EVALUATION OF THE EFFICACY OF THE COMPOSITION

[0145] Experiments in vitrowere also carried out to demonstrate the effects of the C10 and C11 compositions according to the invention. The C12 composition of combination of molecules according to the invention was also tested: dicaffeoylquinic acid + apigenin-7-O-glucuronide + monocafeoylquinic acid + oleuropein + piperine (ratio 1 / 1 / 1 / 1 / 0.001).

[0146] Various enzymatic activity tests were performed to determine whether the compositions according to the invention inhibited strategic enzymes in carbohydrate and lipid metabolism: alpha-glucosidase, DDP-IV, and HMG-CoA reductase. Action on all of these strategic targets allows for comprehensive management of type 2 diabetes and its complications (diabetic foot, retinopathy, vision loss, nephropathy, cardiovascular events, non-alcoholic fatty liver disease, or NASH). → HMG-CoA reductase

[0147] For the control of circulating lipids, the goal is to reduce serum cholesterol concentration by primarily targeting the inhibition of cholesterol biosynthesis (inhibition of 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A or HMG-CoA reductase). Pravastatin is one of the reference molecules for lowering LDL cholesterol and total cholesterol. It is marketed under various brand names, including ELISOR®, PRAVASTATIN MYLAN, VASTEN®, and PRAVASTATIN TEVA. → Alpha-glucosidase

[0148] Alpha-glucosidase is an enzyme that catalyzes the final step in the carbohydrate digestion process. Alpha-glucosidase inhibitors (examples of drugs in this category: GLUCOR®, DIASTABOL®) are used to lower postprandial blood glucose, which is considered an independent risk factor for macrovascular complications in diabetes (Kim JS et al. Biosci Biotechnol Biochem 2000; 64:2458-61). → DPP-IV (dipeptidyl peptidase-IV)

[0149] DPP-IV inhibitors are considered one of the most promising strategies for managing type 2 diabetes (von Geldern TW et al. Drug Development Research 2006; 67:627-42). DPP-IV rapidly inactivates the hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide), also known as incretins. Inhibition of DPP-IV increases the action of GLP-1 and GIP, thereby physiologically stimulating insulin secretion and inhibiting glucagon secretion by the pancreas, and consequently lowering blood glucose levels. Furthermore, DPP-IV inhibition promotes gastric emptying and produces a central anorexigenic effect. Therefore, DPP-IV inhibition allows for better glucose regulation in people with diabetes.Clinical studies also show that DPP-IV inhibitors are highly effective and well-tolerated in managing hyperglycemia in people with type 2 diabetes, without weight gain or hypoglycemic episodes (Green BD et al. Diabetes Vase Dis Res 2006; 3:159-65). One of the reference inhibitors is diprotin A.

[0150] The experimental protocol for evaluating the inhibitory potential of compositions C10, C11, and C12 was as follows: Preparation of extracts, mixtures of extracts and mixtures of pure synthetic molecules

[0151] For the HMG-CoA reductase and glucosidase inhibition tests, the plant extracts were diluted in ultrapure water / ethanol mixtures, the proportions of which varied according to the type of extract, in order to obtain homogeneous solutions.

[0152] After homogenization, the samples were centrifuged at 4000 rpm for 10 minutes and the supernatants were collected (Fisher Bioblock Scientific 1-15 centrifuge, Sigma Aldrich®). The molecules were diluted in either ultrapure water / DMSO 90 / 10 (v / v) or ultrapure water / ethanol 50 / 50 (v / v).

[0153] The mixtures of several plant extracts were diluted in a 50 / 50 (v / v) water / ethanol ratio and then homogenized using ultrasound for 15 minutes (a Hielscher® UP50H ultrasonic probe at maximum power was used). Finally, they were centrifuged at 4000 rpm for 10 minutes, and the supernatants were collected (Fisher Bioblock Scientific 1-15 centrifuge, Sigma Aldrich®).

[0154] In the case of the DPP-IV test, samples were diluted either in Trisma-HCl buffer (pH8.0; 100 mM) or in ultrapure water / DMSO 90 / 10 (v / v). HMG-CoA reductase inhibition assay

[0155] This test measures the effectiveness of enzyme activity inhibition by observing a decrease in absorbance over time at λ=340nm. The reaction mechanism is as follows: HMG-CoA + 2NADPH + 2H+ → mevalonate + 2NADP+ + CoA-SH

[0156] The disappearance of the NADPH substrate (absorbing at 340 nm) is therefore monitored over time. A decrease in the change in absorbance at 340 nm over time compared to the control reaction without inhibitor (100% activity) indicates enzyme inhibition. The first step is to prepare the solutions using the Sigma® kit: The supplied 5X buffer must be diluted to a concentration of 1X in ultrapure water; NADPH is solubilized by the addition of 1X buffer, then dispensed into 100µL tubes; the starting enzyme solution is dispensed into 25µL aliquots.

[0157] The buffer and NADPH were kept at -20°C and the enzyme aliquots were stored at -80°C until use.

[0158] The manipulations were performed directly in 96-well microplates (NUNC96 or SARSTEDT96). Buffers, substrates, inhibitors, and the enzyme were added in a specific order (see below). For each microplate, a blank, a control, and various assays were performed. Each element was prepared in duplicate (or even triplicate): Preparation of the blank: 24 µL of the solvent used for the samples, 12 µL of HMG-CoA, 158 µL of 1X buffer, 4 µL of NADPH; incubation at 37°C, 3 to 5 min; Preparation of the negative control: 24 µL of the solvent used for the samples, 12 µL of HMG-CoA, 158 µL of 1X buffer, 4 µL of NADPH; incubation at 37°C, 3 to 5 min; addition of 2 µL of enzyme; Preparation of the test: 24 µL of the potentially inhibitory sample, 12 µL of HMG-CoA, 158 µL of 1X buffer, 4 µL of NADPH; incubation at 37°C, 3 to 5 min; Add 2 µL of enzyme.

[0159] After plate preparation, kinetic monitoring was performed in a microplate reader (BMG Labtech) over 16 minutes and 25 seconds, with values ​​taken every 25 seconds at λ=340nm, for a total of 40 cycles. From this, the inhibition percentages could be calculated. α-glucosidase inhibition test

[0160] α-glucosidase inhibition assays were performed by spectrophotometrically monitoring, at λ=405 nm, the formation of the yellow para-nitrophenol (PNP) product from the synthetic substrate: para-nitrophenyl-α-D-glucopyranoside (PNPg), according to the following hydrolysis reaction, catalyzed by α-glucosidases: PNPg + H₂O → PNP + glucose

[0161] A decrease in the change in absorbance, at λ=405 nm, over time compared to the control reaction without inhibitor (100% activity) indicates inhibition of the enzyme.

[0162] The recombinant human enzyme produced in Saccharomyces cerevisiae (maltase) (Sigma Aldrich ®, G0660) was diluted in phosphate buffer (0.1 M, pH 6.8) to go from a stock solution theoretically at 120 U / mL, to a solution with an activity of 1.6 U / mL, used for the tests.

[0163] During the α-glucosidase inhibition assays, the procedures were performed directly in 96-well microplates (NUNC96 or SARSTEDT96). Buffers, substrates, inhibitors, and the enzyme were added in a specific order (see below). For each prepared microplate, a blank, a control, and various assays were performed. Each element was prepared in duplicate (or even triplicate): Preparation of the blank: 100 µL of phosphate buffer (0.1 M, pH 6.8), 20 µL of the solvent used for the samples, incubation at 37°C, 10 to 15 min, then addition of 20 µL of PNPg at 2.5 mM (solubilized in phosphate buffer); Preparation of the negative control: 100 µL of phosphate buffer (0.1 M, pH 6.8), 20 µL of the solvent used for the samples, 20 µL of enzymes at 1.6 U / mL, incubation at 37°C, 10 to 15 min, then addition of 20 µL of PNPg at 2.5 mM (solubilized in phosphate buffer); Test procedure: 100 µL of phosphate buffer (0.1 M, pH 6.8), 20 µL of the potentially inhibitory sample, 20 µL of enzyme at 1.6 U / mL, incubation at 37°C, 10 to 15 min, then addition of 20 µL of PNPg at 2.5 mM (solubilized in phosphate buffer).

[0164] After plate preparation, kinetic monitoring was performed in a microplate reader (BMG Labtech) over 30 minutes, with values ​​taken every 2 minutes at λ=405nm, for a total of 16 cycles. From this, the inhibition percentages could be calculated. DPP-IV Inhibition Test

[0165] DPP-IV inhibition assays are performed by spectrophotometrically monitoring, at 385 nm, the formation of the p-nitroaniline product from the synthetic substrate, Gly-L-Pro-p-Nitroanilide, according to the following DPP-IV-catalyzed hydrolysis reaction: Gly-L-Pro-p-Nitroanilide + H₂O → p-nitroaniline + Gly-L-pro

[0166] A decrease in the change in absorbance at 385 nm over time compared to the control reaction without inhibitor (100% activity) indicates enzyme inhibition. The enzyme used was at a concentration of 0.045 U / mL (with U = µmol / min), so it needed to be diluted. Because the dilution was large, two successive dilutions were necessary.

[0167] First dilution (obtaining a solution at 5.10⁴ U / mL): D 1 = 5.10 − 4 ∗ 450 0,045 = 5 μ ⁢ L (Final volume: 450 µL; Volume (Stock enzyme solution) = 5 µL)

[0168] Second dilution (obtaining a solution at 5.10 -6 < U / mL) D 2 = 5.10 − 6 ∗ 1000 5.10 − 4 = 10 μ ⁢ L (Vfinal: 1000 µL ; V(D1)=10 µL)→ solution D2 was the usable solution.

[0169] The manipulations were performed directly in 96-well microplates (NUNC96 or SARSTEDT96). Buffers, substrates, inhibitors, and the enzyme were added in a specific order (see below). For each prepared microplate, a blank, a control, and various assays were performed. Each element was prepared in duplicate (or even triplicate): Preparation of the blank: 25 µL of the sample, 25 µL of substrate (Gly-L-pro-p-nitroanilide solubilized in Tris-HCl buffer (100 mM, pH 8.0) at a concentration of 1.6 mM); preparation of the negative control: 25 µL of the diluent used for the sample, 25 µL of substrate, incubation at 37°C for 10 min, 50 µL of enzyme at 5.10 -6 < U / mL (prepared in Tris-HCl buffer 100 mM, pH 8.0); preparation of the test: 25 µL of potentially inhibitory sample, 25 µL of substrate, incubation at 37°C for 10 min, 50 µL of enzyme at 5.10 -6 < U / mL;

[0170] After plate preparation, kinetic monitoring was performed in a microplate reader (BMG Labtech) over 30 minutes, with values ​​taken every minute at λ=385 nm, for a total of 31 cycles. From this, the percentages of inhibition could be calculated. Calculation of inhibition percentages

[0171] In general, regardless of the test, for a given concentration of an inhibitor, a curve with the equation: absorbance = f(time) (in minutes) was generated. Similarly, controls (without inhibitor) and blanks (without enzymes) were systematically performed. Of the various curves obtained, only the linear portions at the beginning of the kinetics were retained, as they corresponded to the conditions allowing the determination of the initial velocities. Thus, the slope in absorbance / minute was proportional to the rate of product appearance (glucosidase and DPP-IV) or substrate disappearance (HMG-CoA reductase, negative slope).

[0172] Depending on the type of test, the percentages of inhibition of the different enzymes were calculated using different methods: The calculation formula is identical for HMG-CoA reductase and α-glucosidase inhibition tests: % inhibition = pente contrôle − pente échantillon pente contrôle ∗ 100. For the DPP4 inhibition test, the formula is slightly different because blanks are taken into account: % inhibition = pente contrôle − pente blanc − pente échantillon − pente blanc pente contr o ^ le − pente blanc ∗ 100.

[0173] Finally, an average percentage inhibition value was calculated for each inhibitor concentration, along with the standard deviation of each value. If the standard deviation values ​​were greater than 10%, duplicate tests were performed until values ​​below 10% were obtained.

[0174] The results obtained on the three enzymes for compositions C10 and C11 according to the invention are summarized in the Table 16 below. Product Cl 50 a< (µg / mL in well) % inhibition Alpha-glucosidase (Human recombinant Saccharomyces Cerevisiae ) DPP-IV b< (DPP-IV human recombinant expressed in SF9 cells) HMG-CoA reductase c< (Catalytic domain of the human enzyme-recombinant GST fusion protein expressed in E. Coli) Acarbose 86,3 Absence of inhibition Absence of inhibition Diprotein A Absence of inhibition 100% Absence of inhibition Pravastatin Absence of inhibition Absence of inhibition 100% Composition C10 4,3 15,3% 48,5% Composition C11 4,9 29,3% 32,5% a < Cl 50: inhibitor concentration at which the enzyme retains only 50% of its activity. b < Sample concentration set at 1.25 mg / mL. c < Sample concentration set at 60 µg / mL.

[0175] The results obtained on the three enzymes for the association of molecules (composition C12 according to the invention) are summarized in the Table 17 below. Product Cl 50 a< (ng / mL in well) % inhibition Alpha-glucosidase (Human recombinant Saccharomyces Cerevisiae) DPP-IV b< (DPP-IV human recombinant expressed in SF9 cells) HMG-CoA reductase c< (Catalytic domain of the human enzyme-recombinant GST fusion protein expressed in E. Coli) Acarbose 86.3 Absence of inhibition Absence of inhibition Diprotein A Absence of inhibition 89.3% Absence of inhibition Pravastatin Absence of inhibition Absence of inhibition 100% Composition C12 19.7 10.3% 30.1% a < Cl 50: inhibitor concentration at which the enzyme has only 50% of its activity. b < Sample concentration fixed at 250 µg / mL. c < Sample concentration fixed at 60 µg / mL.

[0176] It is observed that, unlike the reference inhibitor molecules of each enzyme [acarbose (drug), diprotin A (reference inhibitor), pravastatin (drug) respectively], the compositions C10, C11 and C12 according to the invention are surprisingly the only ones to inhibit the 3 enzymes.

[0177] By acting simultaneously on several regulatory processes, the compositions according to the invention represent an advantageous means of prevention and treatment for diabetes, dyslipidemia, and their complications. Current therapeutic strategies consist of combining several medications to reduce different risk factors individually. However, drug combinations can sometimes lead to serious side effects, such as the simultaneous administration of fibrates and statins, which increases the risk of myopathy (Denke MA J Manag Care Pharm 2003; 9:17-9). Therefore, there is currently a real need for preventive solutions and medications with a "multi-target" mechanism of action that offers advantages in terms of compliance, tolerability, and efficacy.Thus, the compositions according to the invention make it possible to reduce the risk of cardiovascular diseases and to prevent and treat each dysfunction and / or its consequences taken independently.

Claims

1. A composition comprising at least a mixture of molecules comprising at least: - an extract of Chrysanthellum indicum, and - an extract of Cynara scolymus, and - an extract of Vaccinium myrtillus, and - synthetic piperine and / or an extract of Piper containing piperine, said mixture of molecules comprising: - at least one molecule chosen from apigenin-7-0-glucoronide, chrysanthelline A, chrysanthelline B, caffeic acid, luteolin, maritimetin, eriodictyol, isookanine, apigenin, luteolin-7-0-glucoside, maritimein, marein, eriodictyol-7-0-glucoside, flavomarein, apigenin-8-C-α-L-arabinoside-6-C-β-D-glucoside (shaftoside), apigenin-6,8-C-di-β-D-glucopyranoside (vicenin-2), and - at least one molecule chosen from dicaffeoylquinic acid, sulfomonocaffeoylquinic acid, luteolin, luteolin-7-0-glucoside, luteolin-7-0-glucoronide, apigenin-7-0-glucoside, cynaropicrin, and - at least one molecule chosen from monocaffeoylquinic acid, delphinidin-3-galactoside, delphinidin-3-gluycoside, cyanidin-3-galactoside, delphinidin-3-arabinoside, cyanidin-3-glucoside, petunidin-3-galactoside, cyanidin-3-arabinoside, petunidin-3-glucoside, peonidin-3-galactoside, petunidin-3-arabinoside, peonidin-3-glucoside, malvidin-3-galactoside, malvidin-3-glucoside, malvidin-3-arabinoside, and - at least piperine.

2. The composition according to claim 1, characterised in that the mixture of molecules also comprises an extract of Olea europaea.

3. The composition according to either of the preceding claims, characterised in that the Piper is chosen from Piper nigrum, Piper aduncum and / or Piper longum.

4. The composition according to any of the preceding claims, characterised in that the extract of Chrysanthellum indicum is obtained from the complete plant and / or above-ground parts of Chrysanthellum indicum.

5. The composition according to any of the preceding claims, characterised in that the extract of Cynara scolymus is obtained from the complete plant and / or from leaves of Cynara scolymus.

6. The composition according to any of the preceding claims, characterised in that the extract of Vaccinum myrtillus is obtained from the complete plant and / or from fruits of Vaccinum myrtillus.

7. The composition according to any of the preceding claims, characterised in that it has at least one of the following characteristics: - it comprises a quantity of extract of Chrysanthellum indicum allowing the administration of at least 0.00001 g of extract of Chrysanthellum indicum per kg of body weight of the person to whom the composition is administered and per day, and / or - it comprises a quantity of extract of Cynara scolymus allowing the administration of at least 0.00001 g of extract of Cynara scolymus per kg of body weight of the person to whom the composition is administered and per day, and / or - it comprises a quantity of extract of Vaccinium myrtillus allowing the administration of at least 0.00001 g of extract of Vaccinium myrtillus per kg of body weight of the person to whom the composition is administered and per day, and / or - it comprises a quantity of piperine allowing the administration of at least 0.001 mg of piperine per kg of body weight of the person to whom the composition is administered and per day.

8. The composition according to claim 2, characterised in that it comprises a quantity of extract of Olea europaea allowing the administration of at least 0.00001 g of extract of Olea europaea per kg of body weight of the person to whom the composition is administered and per day.

9. The composition according to any of the preceding claims, characterised in that the composition also comprises at least one molecule chosen from oleuropein and hydroxytyrosol.

10. A composition comprising at least a mixture of molecules, characterised in that said mixture comprises at least dicaffeoylquinic acid, apigenin-7-O-glucuronide, monocaffeoylquinic acid, piperine and oleuropein.

11. The composition according to any of the preceding claims, characterised in that it also comprises at least one supplementary element added in addition to the mixture of molecules, said supplementary element being chosen from: - the following vitamins: B1, B2, B3, B5, B6, B8, B9, B12, C, A, D, E, K1 and K2; - the following compounds: obeticholic acid, corosolic acid, polyunsaturated fatty acids in the omega-6 and / or omega-3 family, orotic acid, pangamic acid, para-amino-benzoic acid, amygdalin, beta-glucans, carnitine, dimethylglycine, imeglimin, isoflavones, L-arginine, oxytocin, pectin, pyridoxamine, resveratrol, viniferine, L-citrulline; - the following oligoelements and minerals: arsenic, boron, calcium, copper, iron, fluorine, iodine, lithium, manganese, magnesium, molybdenum, nickel, phosphorus, selenium, vanadium and zinc; - the following microconstituents of a non-essential nature: conjugated linolenic acid, lipoic acid, carotenoids, carnitine, choline, coenzyme Q10, plant sterols, polyphenols in the tannin and lignan family, and taurine; - fructo-oligosaccharides, galacto-oligosaccharides; - lactic ferments; - yeasts; - fungi; - products derived from insects compatible with the food and pharmaceutical sectors; - marijuana and hashish; - enrobing agents; - flavourings; - acidifiers; - anticoagulants; - thickeners; - stabilisers; - emulsifiers; - fillers; - excipients.

12. The composition according to any of the preceding claims, characterised in that it is in powder, gel or emulsion form, or in liquid form.

13. The composition according to any of the preceding claims, characterised in that it is in the form of tablets, pills, capsules, sticks, sachets, ampoules or droppers, or in injectible form.

14. The composition according to any of the preceding claims, for use as a medication.

15. The composition according to any of claims 1 to 14, for use as a medication or a nutrition product in the prevention of and / or combating against pathological ailments of the glucide and / or lipid metabolism in humans or animals.

16. The composition for use according to claim 14 or 15, in the prevention of and / or combating against type 1 and 2 diabetes and / or non-alcoholic fatty liver diseases and / or cardiovascular pathologies and / or pathologies related to insulin resistance.

17. The composition for use according to claim 16, characterised in that the non-alcoholic fatty liver disease is non-alcoholic hepatic steatosis.

18. The composition for use according to claim 16, characterised in that the cardiovascular pathologies are coronary heart diseases, cerebrovascular ailments, peripheral arteriopathies and deep vein thromboses.

19. The composition for use according to claim 16, characterised in that the pathology related to insulin resistance is Alzheimer's disease.

20. The composition for use according to any of claims 16 to 19, characterised in that it is used in combination with at least one antidiabetic therapeutic agent chosen from biguanides including metformin, dipeptidyl peptidase-IV (DPP-IV) inhibiters, glucagon-like peptide-1 (GLP-1) analogues, thiazolidinediones (TZDs), sulfonylureas, fast and slow insulins, sodium glucose co-transporter-2 (SGLT2) inhibiters, glycosidase inhibiters (acarbose, miglitol, voglibose, peptides containing the alanine-proline or proline-alanine sequence), molecules in the fibranor family such as elafibranor, or molecules targeting the nuclear receptors and in particular the ROR receptors (α, β, γ) and Rev-Erb receptors (α, β).

21. The composition for use according to claim 14 or 15, in the prevention of and / or combating against dyslipidaemia.

22. The composition for use according to the preceding claim, characterised in that it is used in combination with a hypolipidaemic therapeutic agent chosen from: statins, fibrates, nicotinic acid, ion exchange resins, cholesterol absorption inhibiters, polyunsaturated omega-3 fatty acids, tiadenol, and agonists of the FXR nuclear receptor (Farnesoid X receptor).

23. The composition for use according to claim 14 or 15, in the prevention of and / or combating against obesity and excessive weight and / or metabolic syndrome and / or pathological blood-pressure problems.