WO2012080685A1

WO2012080685A1 - Extract of cassia alata against stretchmarks

Info

Publication number: WO2012080685A1
Application number: PCT/FR2011/053058
Authority: WO
Inventors: Agnès DUCROCQ
Original assignee: Teane Cosmetiques
Priority date: 2010-12-17
Filing date: 2011-12-19
Publication date: 2012-06-21
Also published as: FR2968997A1; FR2968997B1

Abstract

The invention relates to an extract of Cassia alata, comprising an amount of flavonoid greater than or equal to 1%, and to the use thereof in cosmetic or pharmaceutical compositions. In particular, the extract according to the invention is appropriate for the treatment of stretchmarks.

Description

Cassia alata extract against stretch marks

The present invention relates to an extract of Cassia alata and its use in cosmetic and pharmaceutical compositions. The compositions according to the invention is more particularly intended to treat a modification of the phenotype of fibroblasts and in particular that resulting in the appearance of stretch marks.

The space surrounding the cells comprises a set of macromolecules, polysaccharides or glycosaminoglycans (GAGs), proteins, salts and water, constituting an extracellular matrix responsible for the cohesion of the tissues. The main structural proteins of this extracellular matrix are collagen and elastin. The constituents of the extracellular matrix are synthesized and secreted in particular by fibroblasts and decomposed by MMP enzymes (Matrix MetalloProteinase) whose activity is inhibited by endogenous TIMP (Tissue Inhibitor of MetalloProteinase) antagonists. TIMPs play a key role in maintaining the balance between extracellular matrix formation and its degradation in various physiological processes.

Collagen (type I and III) gives the tissues their flexibility and is essential for healing processes.

Elastin is a glycoprotein secreted by the cells of the dermis and endowed with elastic properties.

The appearance of stretch marks seems, in general, related to a degradation of the extracellular matrix, in particular by an activation of the fibroblast phenotype in myofibroblasts. Several mechanisms promoting these degradation and activation, acting separately or simultaneously, have been highlighted. Some are detailed below.

A first mechanism would be linked to a first hormonal peak, which leads to an increase in the synthesis of glycosaminoglycans (GAG) and collagen of the extracellular matrix, generating, by its ability to retain water molecules, a problem of structural disorganization. . This structural disorganization has the effect of deteriorating the organization of the matrix and in particular that of the collagen and elastin fibers, causing them to rupture when they undergo tension forces due for example to growth, pregnancy or to a problem of weight. This structural disorganization also causes a loss of elasticity of the skin with a decrease in fibrillin. Fibrillin is a glycoprotein secreted by fibroblasts and a main component of microfibrils, molecules joining together in fibers (elastic or not), characteristics of the connective tissue. It plays a role in the adhesion of the different constituents of the extracellular matrix.

A second mechanism is linked to the presence of mechanical stress. It is especially the case in pregnant women, adolescents or subjects suffering from obesity. Mechanical stress leads to an activation of the phenotype of fibroblasts that turn into myofibroblasts. Since these myofibroblasts are responsible for the contraction of tissues around wounds during a tissue lesion in order to promote their healing, they lead to tissue healing where there is in fact no tissue lesion (a phenomenon subsequently identified by "over-healing"). During the process, the contractile forces operated by the myofibroblasts induce tension resulting in fiber failure. This over-healing then takes on the appearance of a stretch mark.

A third mechanism is linked to an excess of corticosteroids, especially during endogenous stress or the use of corticosteroids. When the stress is prolonged, the protein catabolism causes a destruction of the proteins and a defect of synthesis of the collagen. This having the consequence of blocking the proliferation and metabolism of fibroblasts.

Other mechanisms also seem to favor the degradation of the extracellular matrix and therefore the appearance of stretch marks. Thus, inhibition of the expression of genes encoding fibronectin and type I and III collagen would result in degradation of the extracellular matrix.

The aim of the invention is to provide a means of preventing the degradation of the extracellular matrix and the activation of the fibroblast phenotype and thus of reducing the appearance of stretch marks.

For this purpose, the subject of the invention is an extract of Cassia alata comprising at least one flavonoid, and in which the percentage by weight of flavonoid on the total weight of the Cassia alata extract is greater than or equal to 1.0%. preferably 1.5% and more preferably 2.0%.

The extract according to the invention makes it possible to act on the mechanisms favoring the degradation of the extracellular matrix and of the activation of the fibroblast phenotype and thus of reducing the appearance of stretch marks as evidenced by the experiments detailed in the examples below. . In particular, the extract according to the invention allows:

to limit the proliferation of the cells as much as possible in order to avoid disorganization of the extracellular matrix,

to limit the contraction of the lattice and thus to avoid over-cicatrisation, to control the synthesis of GAG, in particular in order to avoid an increase of it, to control and especially to promote the synthesis of glycoproteins and fibronectin as much as possible to avoid disruption of the extracellular matrix, and finally

to control, in particular to reduce, the amount of smooth muscle actin in order to avoid the activation of the fibroblast phenotype. The extract is obtained from Cassia alata which is an uncommon species of the family Caalpiniaceae. The species Cassia angustifolia, Cassia acutifolia and Cassia senna are common. Cassia alata is a large grassy bush whose leaves are 30 to 60 cm long. The pinnate leaves are arranged alternately with 8 to 12 pairs, are truncated in length and have a length of 5 to 15 cm. The inflorescences appear on small stems and the buds are wrapped in yellow bracts. The Cassia alata is also called Senna alata, zebra moth, breakage breaker, winged breaker or dartrier. Cassia alata is widespread in tropical regions such as India, Indonesia, Africa, America or even Madagascar.

Preferably, the extract is obtainable by extraction from leaves of Cassia alata. Advantageously, Cassia alata is native to Madagascar.

The Cassia alata extract is advantageously in the form of a dry powder. Preferably, the powder is at least 95% dry, that is to say comprises at most 5% water by total mass of the extract.

Such an extract notably comprises flavonoids, mono or di-saccharide sugars, phenolic derivatives such as para-hydroxybenzene acid, anthraquinones and fatty acids.

Preferably, the ratio of the amount by weight of free flavonoid to the amount of glycosylated flavonoid is greater than or equal to 0.1, preferably 0.2 and more preferably 0.3.

Flavonoids, due to the presence of one or more phenol groups, can under certain conditions undergo O-glycosilation. The extract then comprises a fraction of flavonoid in free form (no O-glycosilation) and a fraction in glycosylated form (O-glycosilation of at least one phenolic O).

The subject of the invention is also an extract of Cassia alata obtainable by extraction of Cassia alata by means of a water / ethanol mixture in which the proportion by volume of water / ethanol is between 40/60 and 90/60. 10, preferably between 40/60 and 80/20 and more preferably between 40/60 and 75/25 inclusive. Advantageously, the water / ethanol volume is 50/50 or 70/30, as illustrated in the examples.

The extract obtained with the aid of this extraction process making it possible to act on the mechanisms promoting the degradation of the extracellular matrix and of the activation of the fibroblast phenotype and therefore of reducing the appearance of stretch marks as evidenced by the experiments detailed below. The extraction process makes it possible in particular to obtain an extract as defined above, for example an extract comprising at least one flavonoid and in which the percentage by weight of flavonoid on the total weight of Cassia alata extract is greater than or equal to 1.0%, preferably 1.5% and more preferably 2.0%.

The extract is prepared from known extraction processes using the water / ethanol mixture in the proportions indicated above. Such extraction processes include maceration, remacerization, digestion, shaking maceration, vortex extraction, ultrasonic extraction, countercurrent extraction, percolation, repercolation, extraction. under reduced atmosphere or evacuation, the diacolation, solid / liquid extraction at reflux. Fresh or dried plants, preferably the leaves can be used indifferently.

In the application, "flavonoids" is intended in particular catechin, rutin, quercetin, kaempferol and their substituted derivatives (such as by sugars: derivatives gentiobiosides or sophorosides). Advantageously, the contents indicated in flavonoids are those in kaempferol.

The invention also relates to a composition comprising an extract of Cassia alata as defined above and a cosmetically or pharmaceutically acceptable vehicle.

Indeed, the compositions comprising the extract according to the invention are intended more particularly for a cosmetic, dermatological or pharmaceutical application.

The compositions according to the invention may especially be in the form of a gel, a lotion, an oil, a cream, an emulsion, a milk, a spray, a foam, a bubble bath, a bath-shower composition, an alcoholic solution, a hydro / alcoholic solution, waxes / fat, stick preparations, powders or ointments.

The compositions according to the invention may also comprise at least one of the formulating agents or additives conventional in the following cosmetic and / or dermatological compositions: a UV filter, a softener, a dye, a film-forming active agent, a surfactant, a perfume , preservative, emulsifier, oil, glycol, vitamin, fatty substance, wax, consistency agent, thickener, supergrading agent, stabilizer, polymer, silicone compound, fat , a lecithin, a phospholipid, a biogenic substance, an antioxidant, a film-forming agent, a swelling agent, a self-tanner, a preservative or a perfume.

Preferably, the weight percentage of Cassia alata extract relative to the total weight of the composition is between 0.001% and 10%, preferably between 0.05% and 5% and more preferably between 0.01% and 3%. , terminals included.

Advantageously, the composition further comprises an extract of Centella asiatica.

The extracts are obtained from Centella asiatica which is a species of the family Apiaceae and is also known as Hydrocotyl asiatica L. and various vernacular names, Gotu kola, Antanan, Pegaga, and Brahmi. Centella asiatica is composed of fine green to pink stems forming stolons. The soft green leaves are snappy and have a petiole of about 20 cm. The small hermaphroditic flowers (- 3 mm) are pink and green, arranged in umbels close to the surface of the soil. Each flower is partially contained in a bract. It has 5 stamens and 2 styles. Centella asiatica is widespread in Asia and Oceania.

Advantageously, the percentage by weight of Centella asiatica extract on the total weight of the composition is between 0.001% and 10%, preferably between 0.05% and 5% and more preferably between 0.01% and 3%, terminals included.

As demonstrated in the examples, the combination of the active ingredients of the Cassia alata extract according to the invention with those of an extract of Centella asiatica makes it possible to obtain a particularly effective action on collagen lattices by inhibiting their contraction and therefore to avoid the phenomenon of over-healing due to the activation of the fibroblast phenotype in myofibroblasts.

In addition, the subject of the invention is a process for producing an extract of Cassia alata, comprising at least one step of extracting the extract from Cassia alata by means of a water / ethanol mixture in which the proportion by volume water / ethanol is between 40/60 and 90/10, preferably between 40/60 and 80/20 and more preferably between 40/60 and 75/25 inclusive.

The process according to the invention makes it possible to obtain an extract of Cassia alata which is particularly rich in polyphenols and which makes it possible to act on the mechanisms promoting the degradation of the extracellular matrix and of the activation of the fibroblast phenotype and thus to reduce the appearance of Stretch marks as evidenced by the experiments detailed below.

The invention also relates to the use of an extract according to the invention or a composition according to the invention for a cosmetic application and more particularly for use in the preventive and / or curative treatment of stretch marks.

The preventive action is defined as any action of the extract or composition acting on the inhibition of fibroblast differentiation into myofibroblasts and / or to maintain the integrity and cohesion of the extracellular matrix. Matrix integrity is maintained through inhibition of GAGs and metalloproteases with elastase activity.

The curative action concerns the action of the extract or the composition on a degraded matrix by providing the macromolecules essential for its restoration such as GAGs, proteoglycans, collagen and elastin fibers. The invention is particularly applicable to pregnant women, adolescents or subjects suffering from obesity.

It also relates to an extract of Cassia alata for its application as a medicament in the treatment of diseases involving the differentiation of fibroblasts into myofibroblasts such as idiopathic pulmonary fibrosis.

The invention will be better understood on reading the description which will follow, given solely by way of nonlimiting example and with reference to the drawings in which:

- Figure 1 is a graph illustrating the viability of fibroblasts after application of different compositions;

- Figures 2 to 4 are graphs illustrating the proliferation of fibroblasts after application of different compositions;

FIG. 5 is a graph illustrating the diameter of a lattice of collagen after application of different compositions;

FIG. 6 is a graph illustrating the quantification of GAG glycosaminoglycans after application of various compositions;

FIG. 7 is a graph illustrating the quantification of glycoproteins after application of different compositions;

FIG. 8 is a graph illustrating the expression of the MMP-2 enzyme after application of various compositions,

FIG. 9 presents the results of an immunofluorescence analysis of the effects of different compositions on the synthesis of fibronectin;

FIG. 10 is a graph illustrating the quantification of smooth muscle actin after application of different compositions; and

- Figure 11 illustrates the results of a treatment of stretch marks with two creams containing or not a combination of extracts according to the invention.

Example 1 Process for the Production of Different Compositions

The various compositions A, B, C, A, B 'and C have the following characteristics.

Composition A comprises 2.50% flavonoids, based on the total weight of the dry extract of Cassia alata. Composition A comprises a ratio of the amount of free flavonoids on the amount of glycosylated flavonoids equal to 0.55. Composition A is obtained by extraction of Cassia alata by means of a water / ethanol mixture in which the water / ethanol proportion is substantially equal to 50/50.

Composition B comprises 1.60% of flavonoids, relative to the total weight of the dry extract of Cassia alata. Composition B comprises a ratio of the amount of free flavonoids on the amount of glycosylated flavonoids equal to 0.35. The composition B is obtained by extraction of Cassia alata by means of a water / ethanol mixture in which the water / ethanol proportion is substantially equal to 70/30.

Composition C comprises 0.55% by weight of flavonoids on the total weight of Cassia alata extract. Composition C comprises a ratio of the amount of free flavonoids on the amount of glycosylated flavonoids less than 0.1. The composition C is marketed by the company COGNIS, Monheim (Germany), under the trade name DN Age.

The compositions A, B and C are used at the concentrations (in% by weight of solvent) in extract as indicated in the various examples.

The compositions A, B 'and C respectively comprise the composition A, B, C and

0.01% by total weight of Centella asiatica extract on the total weight of each composition A, B 'and C. The extract of Centella asiatica was obtained from Greenpharma, Orleans (France).

Compositions A and B were prepared by implementing a method according to the invention described below.

Leaves of Cassia alata are harvested, here 10kg of leaves. Then, they are grinded. Then, the crushed leaves are mixed with a water / ethanol mixture in which the water / ethanol proportion is substantially equal to 50/50 (extract of composition A) and 70/30 (extract of composition B).

The mixture is heated for 1 h at 85 ° C with stirring. In order to separate the crushed leaves from the water / alcohol mixture containing the extract, the crushed leaves are filtered off and the water / alcohol mixture containing the extract is filtered on plates. Then, concentrate the water / alcohol mixture containing the extract. Then, the concentrated extract is pasteurized for 20 minutes by autoclaving at 121 ° C. Finally, the extract is spray dried.

EXAMPLE 2 Effects of the extracts according to the invention on the various mechanisms involved in the treatment of stretch marks and comparison with a commercial extract of Cassia alata

1. Experimental model

The experiments relating to the toxicity and to the effects on proliferation of the various compositions are determined in vitro on human dermal fibroblasts.

Effectiveness on the prevention of stretch marks is determined using a collagen lattice model by following lattice contraction over time, differentiating into myofibroblasts and quantifying the synthesis of GAG glycosaminoglycans. The effects of the various compositions on the synthesis of extracellular matrix proteins (collagen, fibronectin, fibrillin) and matrix metalloproteinases MMP (gelatinases A and B) are determined in a 3D fibroblast culture model.

2. Experimental protocols

Cellular culture

Human dermal fibroblasts are cultured in DMEM medium + 10% fetal calf serum until the beginning of the experiments.

Toxicity / Proliferation

Human dermal fibroblasts are seeded in 96-well plates. At about 80% confluency, the cells are incubated in the presence of 6 increasing concentrations of the different compositions. The concentrations are carried out by dilutions in cascade at ½ according to the solubility limit of the extracts of the different compositions. Measurement of lactate dehydrogenase (LDH) activity, released into the culture medium following rupture or damage to the plasma membrane (cytotoxic effect), will be monitored following the reduction of a yellow tetrazolium salt to a compound red colored family of formazans by absorbance measurement at 492 nm.

Lattis of collagen

In order to obtain human dermal fibroblasts cultured in a 0.15% collagen gel, 1 ml of a concentrated 10X DMEM mixture containing sodium bicarbonate is added to 5 ml of a 3 mg collagen solution. ml. The pH is buffered to 7.4 with 0.1 N sodium hydroxide. The cell suspension is added to have 150,000 cells per ml of lath and the final volume is reduced to 10 ml with sterile water. The suspension is then placed in petri dishes 60 mm in diameter untreated for cell culture, at a rate of 4 ml per dish. After polymerization (30 min at + 37 ° C.), the lattice is detached and then covered with 6 ml of DMEM containing 1% fetal calf serum (FCS). The treatment with the different compositions is then carried out. The lattice contraction is observed daily for 7 days and photographed using a Scion camera coupled with Image J (NIH) software for analysis and quantification.

Histological analyzes

At two points of collagen lattice contraction kinetics, biopsies are taken and histological paraffin sections are obtained. The synthesis of the macromolecules of the dermis is determined after staining with Masson trichrome and alkaline blue PAS, respectively. Quantification of macromolecule synthesis is determined by computer analysis using Image J software (NIH) after observation and photography using an optical microscope coupled to a camera. The activation of fibroblasts in myofibroblasts is determined by in situ immuno-detection of the actin alpha isoform of smooth muscle cells.

3D culture of fibroblasts

In order to obtain human dermal fibroblasts cultured in a 0.15% collagen matrix, 1 ml of a concentrated 10X DMEM mixture containing sodium bicarbonate is added to 5 ml of a 3 mg collagen solution. ml. The pH is buffered to 7.4 with 0.1 N sodium hydroxide. The cell suspension is added to have 150,000 cells per ml of lath and the final volume is reduced to 10 ml with sterile water. The suspension is then placed in 60 mm diameter petri dishes treated for cell culture, at a rate of 4 ml per dish. After polymerization (30 min at + 37 ° C.), the 3D gel is covered with 6 ml of DMEM containing 1% FCS. The treatment with the different compositions is then carried out.

Biochemical analyzes

After 48 hours of incubation, conditioned media and cell lysates will be recovered. Expression levels will be determined in conditioned media either by Western blotting for type I collagen, fibronectin, fibrillin, or by gelatin gel zymography for matrix metalloproteinases MMP-2 and MMP-9. The measurement of elastase activity will be determined on the media conditioned using a synthetic substrate (MeOSuc-Ala-Ala-Pro-Valparanitroanilide).

Toxicity of the compositions tested

FIG. 1 illustrates the viability of fibroblasts after application of compositions A, B, C (curves A, B and C) and of a composition comprising an extract of Centella asiatica (AC curve) relative to control fibroblasts as a function of concentration of Cassia alata extract and Centella asiatica. Control is provided by a water-ethanol solution (H20 / EtOH curve). The higher the toxicity, the less the composition is likely to act without altering the viability of the cells. The compositions were tested at different concentrations expressed in% by weight of solvent.

For concentrations below 0.01, none of the compositions exhibits any particular toxicity. For concentrations greater than 0.01, composition A causes the death of nearly 50% of the fibroblasts. For concentrations greater than 0.05, the CA composition also causes the death of nearly 50% of the fibroblasts. Whatever the concentration, composition B has no particular toxicity. For concentrations greater than 0.01, composition B shows no toxicity and even increases the viability of fibroblasts of nearly 50% for a concentration of 0.1.

Effect on the proliferation of fibroblasts

Figures 2, 3 and 4 illustrate the proliferation of fibroblasts after application respectively of compositions A, A '(Figure 2), B, B' (Figure 3) and C, C (Figure 4). The compositions were tested at different concentrations expressed as% by weight of solvent. It is preferable to limit cell proliferation as much as possible to avoid disruption of the extracellular matrix.

Effect of Cassia alata

In FIGS. 2 and 4, compositions A and C make it possible to limit the proliferation of fibroblasts. This effect is particularly significant for a concentration of 0.01%.

On the other hand, in FIG. 3, the composition B has little or no effect on the proliferation activity.

Effect of Centella asiatica

For each composition B, B 'and C, C, the addition of Centella asiatica slightly favors the proliferation of fibroblasts. Thus, according to a general trend, the combination of Cassia alata and Centella asiatica slightly favors the proliferation of fibroblasts.

However, for the compositions A, A ', if the addition of Centella asiatica slightly favors the proliferation of fibroblasts for Cassia alata concentrations lower than 0.01%, for Cassia alata concentrations greater than or equal to 0.01 %, the addition of Centella asiatica favors the inhibition of fibroblast proliferation. Effect on the contraction of a lattice of collagen

FIG. 5 illustrates the collagen lattice diameter after 6 days of incubation in% of control (Ctrl) after application of a composition comprising 0.008% by weight of Cassia alata extract to the total weight of the composition. The control corresponds to a lattice of collagen in which no Cassia alata extract was applied: either the solvent alone (1st stick) or the solvent with Centella asiatica extract (2Nd stick). lattis is a phenomenon occurring during healing. By seeking to limit the contraction of lattice, we try to avoid over-healing.

Effect of Cassia alata

The compositions A, A 'inhibit the contraction of lattice. Compositions B and B 'slightly inhibit lattice contraction. In contrast, compositions C and C promote the contraction of lattice.

Effect of Centella asiatica For the compositions according to the invention A and B, the addition of Centella asiatica (composition A and B ') promotes inhibition of lattice contraction. Conversely, the combination of Centella asiatica with the commercial composition C promotes the contraction of the lattice.

This analysis demonstrates a very particular behavior of Centella asiatica when it is combined with the extracts according to the invention.

Effect on the synthesis of glycosaminoglycans (GAG)

FIG. 6 illustrates the quantification of glycosaminoglycans GAG after 6 days of incubation in% of the control after application of a composition comprising 0.008% by weight of Cassia alata extract on the total weight of the composition. The control (Ctrl) corresponds to a medium in which no Cassia alata extract was applied: either the solvent alone (1 st stick) or the solvent with Centella asiatica extract (2Nd stick). It is preferable to control, in particular to inhibit, the synthesis of GAGs as much as possible in order to avoid disruption of the extracellular matrix due to the retention of water molecules by GAGs if efficacy is sought on the prevention of stretch marks.

Effect of Cassia alata

The compositions A, A 'inhibit at least 50% the synthesis of GAG. Compositions B and B 'have little or no effect on GAG synthesis. On the contrary, the commercial composition C and the composition C promote the synthesis of GAGs.

Effect of Centella asiatica

The addition of Centella asiatica has little or no effect on GAG synthesis.

Effect on glycoprotein synthesis

FIG. 7 illustrates the quantification of the glycoproteins after 6 days of incubation in% of the control after application of a composition comprising 0.008% by weight of Cassia alata extract on the total weight of the composition. The control (Ctrl) corresponds to a medium in which no composition has been applied. It is preferable to control, in particular to promote, the synthesis of glycoproteins as much as possible to avoid disorganization of the extracellular matrix.

Effect of Cassia alata

The compositions A, A 'strongly favor the synthesis of glycoproteins. On the other hand, compositions B, B ', C and C favor only weakly the synthesis of glycoproteins.

Effect of Centella asiatica

The addition of Centella asiatica does not seem to have any effect on the synthesis of glycoproteins (composition B, Β ', C and C). In contrast, for composition A, the addition of Centella asiatica significantly favors the presence of glycoproteins. Thus, the combination of a Cassia alata extract obtained by an extraction process according to the invention with a water / ethanol volume ratio of 50-50 with an extract of Centella asiatica therefore has an unexpected effect.

Effect on the expression of the enzyme MMP-2

FIG. 8 illustrates the expression of the MMP-2 enzyme (Matrix MetalloProteinase type 2) in% of the control after application of a composition comprising 0.008% by weight of Cassia alata extract to the total weight of the composition. The control (Ctrl) corresponds to a medium in which no composition has been applied. The MMP-2 enzyme plays a key role in maintaining the balance between extracellular matrix formation and its degradation in various physiological processes. It is preferable to control the enzyme synthesis as much as possible to avoid disruption of the extracellular matrix due to an increase or decrease in the amount of the enzymes in the extracellular matrix.

Effect of Cassia alata

Compositions A, A block the expression of MMP-2 by at least 50%. In contrast, compositions B, B 'and C, C have little or no influence on the expression of MMP-2.

Effect of Centella asiatica

Whatever the composition, the addition of Centella asiatica has no effect on the expression of MMP-2. Effect on the synthesis of fibronectin

Tests on the effect of the various compositions on the synthesis of fibronectin are presented in FIG. 9. For each composition, a composition comprising 0.006% by weight of Cassia alata extract is applied to the total weight of the composition. The results of these tests were visualized by immunoflurescence. Fibronectin contributes to the organization of extracellular matrix and cell adhesion. Thus, it is preferable to control, in particular to promote, the synthesis of fibronectin as much as possible to avoid disorganization of the extracellular matrix.

Effect of Cassia alata

In the absence of Centella asiatica, all compositions inhibit the synthesis of fibronectin.

Effect of Centella asiatica

The presence of Centella asiatica (composition A) does not modify the However, the presence of Centella asiatica modifies the behavior of compositions B and C: composition B 'significantly promotes the synthesis of fibronectin as well as composition C to a lesser extent.

Effect on smooth muscle actin (alphaSMA)

FIG. 10 illustrates the quantification of smooth muscle actin (alphaSMA) in% of the control after application of a composition comprising 0.006% by weight of Cassia alata extract to the total weight of the composition. The control (Ctrl) corresponds to a medium in which no composition has been applied. Smooth muscle actin has the main functions of cell motility, cytokinesis, phagocytosis, adhesion, cell morphology and provide structural support. It is therefore sought to inhibit the amount of smooth muscle actin in order to avoid the activation of the fibroblast phenotype in myofibroblasts.

Effect of Cassia alata

Significant inhibition of the amount of smooth muscle actin for the compositions A, A 'is observed. Slight inhibition is also observed for compositions B, B '. In contrast, the composition C, C have the effect of increasing the amount of actin.

Effect of Centella asiatica

Whatever the composition, the addition of Centella asiatica has little or no effect on the amount of smooth muscle actin.

Example 3 Comparison between a cream formulated from excipients containing or not a combination of extracts of Cassia alata.

Mode of realization

Clinical tests were randomly conducted in double blind on ten subjects in hospital with a cream formulated with excipients not containing the active ingredients of Cassia alata and Centella asiatica (cream # 1) and with a cream containing these combined extracts at concentrations greater than 0.1% in the cream (cream No. 2).

Effects observed on the appearance of stretch marks by subjects

The subjects were asked about the state of their stretch marks after treatment with creams n ° 1 and n ° 2 according to well-defined criteria of stretch marks, reduced length of stretch marks and stretch marks. The results concerning the opinion of the subjects on the creams that they tested are referenced in the table below: Attenuated stretch marks Length Stretch marks diminished Stretch marks finer

CREAM 1 CREAM 2 CREAM 1 CREAM 2 CREAM 1 CREAM 2

Strongly agree 3 2 Strongly agree; 1; 1 Strongly agree; 1 0

Okay 1; 6 OK 2 ^; 5 Agreement 3 6

Disagree 5 1 Disagree 6d 3 Disagree 5 3

Strongly disagree 1 1 Strongly disagree 1; 1 Not at all 1 1 total 10 10 10! 10 10 at least Agree 40: 80% at least Agree; 30%; at least agree; 40% §0% at least No acco 60%; 20% at least No accc 70%; 40% at least No Ace 60% 40%

FIG. 11 illustrates using sectoral graphs (A, B, C) the results obtained in the table above.

The results obtained with Cream No. 1 are shown in FIG. 11:

A1 illustrates the results for attenuated stretch marks,

B1 illustrates the results for the diminished length of stretch marks,

C1 illustrates the results for the finest stretch marks.

The results obtained with Cream No. 2 are shown in FIG. 11:

A2 illustrates the results for attenuated stretch marks,

B2 illustrates the results for the diminished length of stretch marks,

C2 illustrates the results for the finest stretch marks.

Conclusion

The results obtained show a very marked improvement in the stretch marks in the subjects having tested cream No. 2 containing the combination of extracts of Cassia alata and Centella asiatica as described in the invention, unlike the subjects who used cream n ° 1 not including any of these extracts.

Claims

1. Cassia alata extract comprising at least one flavonoid, wherein the weight percentage of flavonoid on the total weight of Cassia alata extract is greater than or equal to 1% and the ratio of the amount of free flavonoid to the amount of flavonoid glycosylated is greater than 0.1.

2. A composition comprising an extract of Cassia alata according to claim 1 and a cosmetically or pharmaceutically acceptable vehicle.

3. Composition according to claim 2, wherein the weight percentage of Cassia alata extract on the total weight of the composition is between 0.001% and 10%.

4. Composition according to claim 2 or 3, further comprising an extract of Centella asiatica.

5. Composition according to claim 4, wherein the percentage by weight of Centella asiatica extract on the total weight of the composition is between 0.001% and 10%.

6. Use of a Cassia alata extract according to claim 1, or a composition according to any one of claims 2 to 4, for the preventive and / or curative treatment of stretch marks.

7. Cassia alata extract for its application as a medicine in the treatment of diseases involving the differentiation of fibroblasts into myofibroblasts such as idiopathic pulmonary fibrosis.