Technical field The present invention relates to a method of controlling weight gain of a subject, said method comprising administering a composition comprising or consisting of at least one extract of aerial parts of a Narcissus spp. plant as an active ingredient to said subject. Furthermore, the present invention refers to the use of such composition for controlling weight gain of a subject and to such composition for use in a method for of controlling weight gain of a subject.

The present invention further relates to com postions comprising Narcissus spp. plant extract and use thereof. It further relates to compositions for preventing and/or treating obesity and/or metabolic syndrome comprising Narcissus spp. plant extract. Moreover, the present invention relates to compositions for preventing and/or treating obesity and/or metabolic syndrome comprising a Narcissus spp. plant extract. The Narcissus spp. plant extract, which is the active ingredient of the present invention, may inhibit an increase in the number of adipocytes and lipid accumulation by inhibiting adipocyte differentiation, inhibit excessive secretion of adipocyte-derived lipids, is a safe substance having no skin irritation and cytotoxicity, and is useful for a pharmaceutical composition, a food composition, a skin external preparation composition and a cosmetic composition for the prevention, amelioration and treatment of obesity, metabolic syndrome and, more generally for improving the overall skin properties. Background of the invention

Worldwide, obesity has increased rapidly and is known to be a significant cause of chronic diseases such as hypertension, hyperlipidemia, and diabetes. The World Health Organization has defined obesity as a 21 ^st century epidemic/pandemic, and the prevalence of obesity in the world more than doubled between 1980 and 2014. Although the mortality rate from obesity has increased worldwide, obesity is preventable (WHO, 2014). In Korea, 32.5% of adults are obese, and 2 out of 5 adult men and 1 out of 4 adult women are obese, which is a serious problem that threatens national health (Health and Nutrition Examination Survey, 2014).

Obesity refers to a phenomenon in which excess calories are accumulated as fats in the body by ingesting more calories than the calories consumed. The World Health Organization (WHO) reported that about 400 million people in the world over the age of 15 are classified as obese, and 1.6 billion people are overweight (September 2006). In line with this trend, obesity has emerged as a severe social problem, not just an individual disease. Obesity is known to be caused by genetic factors, environmeltal and/or lifestyle factors resulting from westernized dietary habits, and psychological factors resulting from stress, but the exact cause or mechanism of obesity has not been clearly identified.

The goals of obesity treatment are broadly divided into two. One goal is to lose weight by burning excess fat, and a further goal is to improve metabolic imbalance. Abdominal obesity is closely related to symptoms such as insulin resistance, type 2 diabetes, hypertension, and lipid metabolism, and acts as a strong risk factor for early arteriosclerosis, ischemic heart disease, and cerebrovascular disease (Kopleman P.G., Nature, 404, 2000; Manson et al., New England J. Med., 333, 1995; Must et al., JAMA, 282, 1999). Thus, currently, the treatment of obesity aims not only at losing weight but also at ameliorating metabolic abnormalities by early eliminating factors that cause cardiovascular disease. Studies focused on suppressing obesity by controlling dietary intake control and energy consumption have also been actively conducted. Hypothalamus, motor nervous, autonomic nervous, and peripheral nervous systems are all involved in regulating food intake behaviors, and the central nervous system, especially the hypothalamus, plays an important role in the etiology of obesity. Typical factors secreted from the hypothalamus include neuropeptide Y, POMC/CART, melanocortin receptor, norepinephrine, serotonin, and the like. Current strategies for developing obesity therapeutic agents include reducing food intake, inhibiting calorie absorption, promoting exothermic reactions, regulating energy metabolism, and regulating signal transduction through the nervous system (Mi-Jung Park, Korean J Pediatr 48(2), 2005).

Among obesity therapeutic drugs known to date, the most representative drugs include Xenical™ (Roche Pharmaceuticals, Switzerland), Reductil™ (Abbott, USA), Exolise™ (Arkopharma, France), and the like, but cause adverse effects such as cardiac diseases, respiratory diseases, neurological diseases and the like. The persistence of efficacy thereof is low. Accordingly, the search for safer and more effective anti-obesity substances is ongoing.

Caffeine is a well known slimming ingredient (also designatable as slimming agent) which can be incorporated in many formulation forms such as topical, nutraceutical compositions. Precisely, caffeine is an alkaloid, enables to prevent the excessive accumulation of fat in adipose tissue, to stimulate the lipolysis, to degrade triglycerides and, thus, it takes part in the reduction of fat-related skin damages such as cellulitis for example. Fat stored in adipocytes is used as an important energy source in the body, but as obesity progresses, the number of adipocytes increases and adipocytes differentiate. As adipocytes differentiate, the synthesis of triglycerides increases. It is known that triglycerides accumulated and stored in adipocytes increase the size of adipocytes, and the diameter of adipocytes may increase about 20 times due to the storage of fat therein, and as a result, the cell volume increases several thousand times. This size of adipocytes may be controlled by dietary control, but the process in which new preadipocytes differentiate into adipocytes is not effectively controlled by dietary control. Thus, for the fundamental treatment or inhibition of obesity, it is important to control the adipocyte differentiation process of adipocytes.

Another way to tackle obesity, is to stimulate the “browning” of white adipose tissue (WAT). In contrary to white adipose tissue, the brown adipose tissue (only present in the first few months of human life) contain cells with smaller fat droplets and are more energetically active due to their greater number of mitochondria. Brown adipocytes express a protein called uncoupling protein 1 (UCP-1 ) localized to the mitochondria membranes where it short-circuits the pathway to produce energy. This energy is then dissipated for heat production in response to cold. Thereby, heat is produced while energy is consumed which eventually leads to the elimination of fat deposits. Thus, activating the browing of white adipose tissue through the stimulation of UCP-1 expression would lead to an increase in fat burning without additional exercise. Interestingly, an adipose tissue similar to brown adipose tissue can be seen in adults when they are subjected to low temperatures and exercise. This brown adipose tissue-like is called “beige adipose” tissue. Beige fat arises from white fat (precursors or mature cells). Despite this common origin, beige fat is thermogenic, like brown fat, so it plays a different metabolic role than white fat. The term “browning” describes the emergence of beige adipocytes in WAT, a reversible process that represents adaptation to increased thermogenic demand and exercise.Thanks to the plasticity of the adipose tissue, improving obesity state may be expected.

Moreover, the expansion of adipose tissue in obesity is accompanied by the accumulation of immune cells that contribute to a state of chronic inflammation and dysregulated metabolism such as the insuline resistance, the impairment of adipocyte function. Adipose tissue macrophages represent the most abundant class of immune cells in adipose tissue and are involved in the regulation of several regulatory physiological processes, such as tissue remodeling and insulin sensitivity. It has been shown that macrophages recruited from blood monocytes are critical components of the generation of adipose tissue inflammation, but their proliferation plays a role in the early stages of obesity and in sustaining adipose tissue inflammation (Russo and Lumeng, Immunology 2018).

Consequently, a disproportionately increase of pro-inflammatory macrophages in WAT is associated with obesity and compromises the adipose tissue homeostasis by promoting the adipocyte hypertrophy, the altered secretion profile of adipocytes, the metabolic dysfunction and the excessive deposition of collagen fibers around adipocytes, so called peri-adipocyte fibrosis, which reinforce the macrophage increase in adipose tissue and perpetuate a vicious cycle with the maintenance of fibro-inflammation in adipose tissue of an obese or an overweight person. Additionally, it is also known that the adipose tissue of obese or an overweight person is mainly constituted by enlarged adipocytes. It has been reported that adipocyte enlargement was significantly decreases the dermal elasticity (Ezure et al., Experimental dermatology, DO1 10.1111 ; 2015). More generally, it has been shown that obesity is an aggravating factor for skin properties (Mori et al., Lipids in Health Disease, DO1 10.1186; 2017). Indeed, the authors showed a reduction of the moisturizing and barrier functions of the skin, and an inflammation-like symptom including redness and roughness. However, adipocytes contribute to various skin functions and their ability to perform many of their functions is influenced by their stored lipids. Indeed, it is agreed that dermal fibrosis involves the deposition of excessive extracellular matrix and the loss of adipocytes.

Meanwhile, Narcissus spp. plants are perennial plants belonging to the Narcissus family and are collectively referred to as narcissus. Narcissus is planted as bulbs in winter and blooms mainly in spring. Bulbs of narcissus are toxic and are used as a disinfectant for boils or swelling, flowers thereof are used to produce perfumed oil, and scaly stems thereof are used as a therapeutic agent as an expectorant of whooping cough. It has been reported that microniosomes, including narcissus bulbs, exhibit a wound healing effect by promoting the proliferation and migration of fibroblasts (Ramaesh M et al., Daru 2018 Sep 12. DOI: 10.1007/s40199-018-0211 -7) and have an anticancer effect (Rezadoost MH et al. , Mol Biol Rep. 201946(5):5131-5142). In addition, KR-A 10-2016-0114794 discloses that a narcissus bulb extract has the effects of improving skin elasticity, reducing wrinkles, and reducing skin irritation, and KR-B 10-1807978 discloses a composition containing a Narcissus spp.-derived peptide that activates Sirt6. However, the adipocyte differentiation regulatory effect suggested by the present invention has not yet been reported.

Therefore, there is still a need to provide an extract of Naricissus spp. plant capable to exert, not only, a slimming effect, but also to regulate the impaired metabolic and endocrine functions of the adipose tissue, and thus, more generally a product capable to improve the overall skin properties, particularly its physiology and its aspect. Accordingly, the present inventors have made efforts to find a natural product-derived substance that has excellent anti-obesity, anti-fat effects, an homeostasis regulating effect on adipose tissue, without having side effects, and as a result, have found that a Narcissus spp. plant extract (e.g., an extract of the aerial parts of Narcissus spp. plant) exhibits an excellent anti-obesity effect, for example, by controlling the number of produced adipocytes through the regulation of adipocyte differentiation and releasing excess energy accumulated, thereby completing the improvement of the overall skin properties.

Summary of the invention

Surprisignly, it has been found that an extract of the aerial parts of Narcissus spp. plant can be used as a slimming ingredient. Further, it has surprisignly been found that a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant can be used for preventing and/or treating obesity, for preventing and/or treating fat-related disorders in adipose tissue, for preventing and/or alleviating or treating the fat-related skin disorders or damages. Hence, the at least one extract of the aerial parts of Narcissus spp. plant is useful to comply with the improvement of the overall skin properties.

Accordingly, an aspect of the present invention is a method of controlling weight gain of a subject, said method comprising administering a composition comprising or consisting of at least one extract of aerial parts of a Narcissus spp. plant as an active ingredient to said subject.

The method may be any method, including a cosmetic method (also: non-pharmaceutical, non-therapeutic) or a therapeutic (also: pharmaceutical) method.

One object of the present invention is to provide a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant as an active slimming ingredient. Thus, in a preferred embodiment, the extract of aerial parts of a Narcissus spp. is an active slimming ingredient.

Another object of the present invention is to provide a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant for use for preventing and/or treating obesity or fat-related disorders, for preventing and/or alleviating or treating the overweight-related skin damages seleted from cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight- related skin.

Another object of the present invention relates to a cosmetic use of a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant as an active ingredient for promoting or restoring the adipose tissue homeostasis, for treating or alleviating the overweight-induced skin damages selected from cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight-related skin.

Another object of the present invention is to provide a pharmaceutical composition for preventing and/or treating obesity and/or metabolic syndrome comprising a Narcissus spp. plant extract (e.g.,an extract of the aerial parts of Narcissus spp. plant). In an embodiemnt of the present invention, the method is a method of preventing, ameliorating, or treating obesity and/or metabolic syndrome.

Another object of the present invention is to provide a skin external preparation composition for preventing and/or treating obesity comprising a Narcissus spp. plant extract.

Still another object of the present invention is to provide a food composition for preventing or ameliorating obesity and/or metabolic syndrome comprising a Narcissus spp. plant extract.

Yet another object of the present invention is to provide a cosmetic composition for preventing or ameliorating obesity comprising a Narcissus spp. plant extract (e.g., an extract of the aerial parts of Narcissus spp. plant).

Still another object of the present invention is to provide a food or nutraceutical composition comprising (or consisting of) an extract of the aerial parts of Narcissus spp. plant for preventing or ameliorating obesity or fat-related disorders, for preventing and/or alleviating or treating the overweight-related skin damages selected from cellulites, lymphedema, striae and tissue fibrosis, and/or for preventing or ameliorating metabolic syndrome.

A further object of the present invention is to provide a cosmetic method for promoting or restoring the adipose tissue homeostasis, for preventing and/or alleviating or treating the overweight-induced skin damages selected from cellulites, lymphedema and striae, and/or for promoting the firmness and the texture of the overweight-related skin by administering to a subject in need, preferably in subject’s area in need, a sufficient amount of a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant as an active slimming ingredient.

Still yet another object of the present invention is to provide a method of preventing, ameliorating, or treating obesity and/or metabolic syndrome using a composition comprising (or consisting of) a Narcissus spp. plant extract.

Detailed description of the invention

The present invention relates to compositions for preventing, ameliorating, and treating obesity or fat-related disorders and/or metabolic syndrome comprising a Narcissus spp. plant extract (e.g., an extract of the aerial parts of Narcissus spp. plant) as an active ingredient. More specifically, the present invention relates to a pharmaceutical composition, a skin external preparation composition, a cosmetic composition and a food (or nutraceutical) composition, which each comprise a Narcissus spp. plant extract (e.g., an extract of the aerial parts of Narcissus spp. plant) as an active ingredient. The compositions are highly safe for humans without having skin irritation and cytotoxicity, and may inhibit adipocyte differentiation, reduce the number of adipocytes, and may effectively inhibit lipid accumulation and excessive secretion of adipocyte-derived lipids. In addition, the compositions enable to regulate the impaired metabolic and endocrine functions of the adipose tissue. It will be understood that, in a composition consisting of Narcissus spp., the composition is the extract.

An aspect of the present invention relates to a composition comprising (or consisting of) at least one Narcissus spp. plant extract (e.g., extract of the aerial parts of Narcissus spp. plant) as an active slimming ingredient. An aspect of the present invention provides a pharmaceutical composition for preventing and/or treating obesity or metabolic syndrome comprising at least one extract of a Narcissus spp. plant extract (e.g., an extract of the aerial parts of Narcissus spp. plant).

According to an embodiment of the invention, the Narcissus spp. plant is selected from the group consisting of Narcissus tazetta L, Narcissus jonquilla L, and Narcissus Pseudo- Narcissus L. In a preferred embodiment of the invention, the Narcissus spp. plant is Narcissus jonquilla L.

As used herein, the term "extract" refers to products such as liquid products obtained by immersing materials including plants in various solvents, and then performing extraction and fractionation in a room temperature or elevated temperature state for a predetermined time, or solid products obtained by removing the solvents from the liquid products. In addition to the above-described products, the term “extract” may be interpreted as including all dilutions of the products, concentrates thereof, crude products thereof, and purified products thereof.

In the present invention, the “Narcissus spp. plant extract” is obtained by extraction from the leaf, flower, stem, root and the like of the Narcissus spp. plant, preferably the flower, leaf, and stem of the Narcissus spp. plant. Prefreably, it is at least one part of the aerial part of the Narcissus spp. plant. Preferably, the “Narcissus spp. plant extract” is obtained by extraction from the aerial parts of the Narcissus spp. plant, preferably from the leaf, flower, stem and the like of the Narcissus spp. plant.

According to an embodiment of the present invention, the aerial part of the Narcissus spp. plant may be selected from the leaves, the stems, the flowers, or a combination of two or more thereof. Preferably, the aerial part of the Narcissus spp. plant comprises stems and/or flowers.

In an embodiment of the present invention, the aerial part of Narcissus spp. is characterized in that:

(i) it is an aqueous, a hydroalcoholic, or an alcoholic extract; and/or

(ii) it comprises at least 0.05% by weight (also “wt%), preferably at least 0.1 % by weight, more preferably at least 0.15% by weight, particularly at least 0.2% by weight of dry matter, referred to the total weight of the extract.

In the present invention, the Narcissus spp. plant extract may be obtained by extraction with water or any organic solvent. At this time, the organic solvent may preferably be water, a polar solvent, or a non-polar solvent, but the solvent is not limited thereto as long as an extract having the effects of inhibiting adipocyte differentiation, inhibiting lipid accumulation of adipocytes and excessive secretion of adipocyte-derived lipids, restoring the adipose tissue homeostasis, alleviating the overweight skin damages and promoting the firmness of the overweight-related skin may be obtained.

In this context, an alcohol contained in a hydroalcoholic or alcoholic extract may be any alcohol. Preferably, an alcohol contained in a hydroalcoholic or alcoholic extract is selected from the group consisting of ethanol, methanol, propanol, butanol, pentanol, phenol, glycerol, 1 ,3-butylene glycol, propane diol, or a mixture of two or more thereof, in partilcar wherein an alcohol contained in a hydroalcoholic or alcoholic extract is ethanol; At this time, the organic solvent may preferably be water, a polar solvent, or a non-polar solvent, but the solvent is not limited thereto as long as an extract having the effects in the spirit of the disclosure of the present invention may be obtained. More preferably, the solvent may be water, C1-C4 lower alcohol (e.g., selected from ethanol, methanol, propanol, butanol), pentanol, phenol, glycerol, 1 ,3-butylene glycol, propane diol or a mixture of two or more thereof. Preferably, the solvent may be a mixture of water and ethanol or a mixture of water and methanol. More preferably, the solvent may be an alcohol selected from methanol and ethanol. Optionally, the solvent may be a mixture of water and ethanol.

In a preferred embodiemnt, the at least one extract of aerial parts of Narcissus spp. is an aqueous extract which is obtained by extracting the aerial parts of Narcissus spp. with hot water of a temperature of 25 to 200°C, of 50 to 175°C, of 60 to 150°C, of 70 to 140°C, of 80 to 130°C, or of 90 to 120°C.

For instance, the temperature used in this context may in the range of 50 to 70°C, of 60 to 90°C, of 90 to 100°C, of 100 to 110°C, of 110 to 120°C, or of 100 to 150°C.

In a preferred embodiment, extracting the aerial parts of Narcissus spp. with hot water (also designatable as “the hot water extraction) is conducted under reflux.

Such extraction under reflux may be conducted 1 time (i.e., once), 2 times (i.e., twice),

3 times, 4 times, 5 times, or more that 5 times. The expression “times” in this context may also be designated as “in extraction cycles” In a preferred embodiment, extracting the aerial parts of Narcissus spp. with hot water is conducted 1 time, 2 times or 3 times, in particular

3 times. Extraction under reflux may be conducted for a time sufficient for extraction. For instance, one extraction (cycle) may be conducted for a time range of from 1 min to 24 h, of from 5 min to 12 h, of from 10 min to 6 h, of from 15 min to 3 h, of from 15 min to 1 h, or of from 15 min to 45 h, or of from 20 min to 35 h. The total time for extraction may be performed within 5 min to 24 h, of from 10 min to 12 h, of from 15 min to 12 h, of from 30 min to 6 h, of from 90 min to 5 h, of from 2 h to 4 h, of from 2 h to 3 h.

In a preferred embodiment, extracting the aerial parts of Narcissus spp. with hot water is conducted at 90 to 120°C, 3 times under reflux, wherein each reflux may last 20 to 35 min, and the procedure optionally is conducted during 2 hours.

In addition, a method for obtaining the extract is not particularly limited as long as it may provide an extract having the effects of inhibiting adipocyte differentiation and inhibiting lipid accumulation of adipocytes or excessive secretion of adipocyte-derived lipids, restoring the adipose tissue homeostasis, alleviating the overweight skin damages and promoting the firmness of the overweight-related skin. In addition, a method for obtaining the extract is not particularly limited as long as it may provide an extract having the effects in the spirit of the disclosure of the present invention. Examples of the extraction method may include hot water extraction, cold water extraction, ultrasonic extraction, and reflux cooling extraction methods. Extraction may preferably be performed by the ultrasonic extraction method.

The ultrasonic extraction is a method of extracting useful components from various natural materials at room temperature by a physical force rather than chemical force using a vibrating element having a vibration frequency of 20,000 times or more per second. Unlike solvent extraction, vegetable oil extraction, or steam distillation extraction, the ultrasonic extraction has the advantage of being able to extract high concentrations of active ingredients from natural materials at room temperature without destroying the active ingredients.

In one exemplary embodiment, the ultrasonic extraction may be performed on the dried powder of the aerial part of a Narcissus spp. plant using a 60% to 80% (by volume) ethanol solution at room temperature for 24 to 72 hours. Preferably, the ultrasonic extraction may be performed using a 50% to 90% (by volume), preferably a 65% to 75% (by volume) ethanol solution at room temperature for 36 to 60 hours. More preferably, the ultrasonic extraction is performed using a 60 to 80% (by volume), preferably 70% ethanol solution at room temperature for 20 to 50 hours, preferably for 25 to 45 hours, more preferably for 40 hours. In one embodiment, if the ethanol concentration and the extraction time are lower than the lower limits of the above-described ranges, the active ingredient of the present invention, contained in the aerial part of the Narcissus spp. plant, will not be sufficiently extracted. If the ethanol concentration and the extraction time are higher than the upper limits of the above-described ranges, there will be no significant difference in the amount of the active ingredient extracted, impurities will be extracted in addition to the active ingredient, and the efficiency of the extraction process will be reduced.

In another specific embodiment, the hot-water extract is performed on the dried powder of the aerial parts of the Narcissus spp. plant in purified water at high temperature, preferably 100 to 150°C, more preferably 100 to 130°C, even more preferably 110 to 130°C, most preferably 121 °C, for 20 minutes to 1 hour, preferably 20 minutes to 50 minutes, more preferably 20 minutes to 40 minutes, most preferably 30 minutes. The obtained Narcissus spp. plant extract may be concentrated under reduced pressure using, but not limited to, a vacuum concentrator or a rotary vacuum evaporator. In addition, after vacuum concentration, the extract may be dried through, but not limited to, freeze drying, reduced-pressure, vacuum drying, boiling drying, or spray drying. As used herein, the term “dry extract’ may be understood in the broadest sense as a dry matter (physical form) without the solvent.

As used herein, the expression “adipose tissue homeostasis” means that the adipose tissue having its normal or healthy state in terms of cell proliferation, cell death, and its metabolic function.

As used herein, the term “cellulites” also known as “orange peel”, is characterized by an uneven skin profile affecting the tissue around the thighs, buttocks and hips, the areas where adipose tissue is deposited in the largest amounts in a subject. The dimply appearance is caused by the extension of the fat tissue into the fibrous connective tissue. Larger fat deposits exacerbate this problem as the pressure from the fat onto the connective tissue increases. As used herein, the term “striae or striae distensae”, also known as stretch-marks, is a skin defect caused by excessive stretching of the skin in areas with large amounts of adipose fat tissue, such as the breasts, buttocks, abdomen, hips, thighs and underams. They appear first as erythematous linear bands, which turn purple and then white overtime, becoming atrophic and depressed. Overweight, particularly obesity is one of the fastest bringers of striae as it involves rapid growth which the skin is less likely to keep up this evolution.

The Narcissus spp. plant extract which is an active ingredient of the present invention has the general beneficial effects of restoring or promoting the adipose tissue homeostasis, treating or alleviating the overweight-induced skin damages, particularly by controlling adipogenesis by inhibiting adipocyte differentiation, reducing the number of (mature) adipocytes, inhibiting the accumulation and excessive secretion of (adipocyte-related) lipids, promoting lipolysis of adipocytes, by promoting the conversion of white adipocytes into brown adipocytes, by controlling the structure of the dermal extracellular matrix, by counteracting the inflammation of the adipose tissue and by controlling the secretion of adipokines. Indeed, by achieving the aforementioned activities and functions, the extract of the aerial parts of Narcissus spp. according to the present invention can be used as an ingredient to comply with the slimming purposes, more generally to improve the overall skin properties, particularly its physiology and aspect. In one specific example, it was confirmed that an ethanol extract of an aerial part of a Narcissus spp. plant has the effects of inhibiting an increase in the number of adipocytes by inhibition of adipocyte differentiation and inhibiting lipid accumulation and secretion by inhibiting the production of adipocyte-derived lipids (FIGS. 1 and 10). Therefore, the composition comprising the Narcissus spp. plant extract according to the present invention is effective in inhibiting adipocyte differentiation, inhibiting accumulation of adipocyte-derived lipids, and inhibiting excessive secretion of adipocyte-derived lipids, and thus is useful for the prevention, amelioration and treatment of obesity and metabolic syndrome.

As used herein, the term "obesity" refers to a condition in which the number of adipocytes is above average and lipids are excessively accumulated in adipocytes.

As used herein, the term "metabolic syndrome" refers to a disease caused by obesity or at least over-weight, or at least having a high correlation with them (e.g. obesity). For example, the metabolic syndrome may be, but is not necessarily limited to, any one selected from among fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis, and lipid-related metabolic syndrome. The lipid-related metabolic syndrome refers to a disease in which various metabolic syndromes such as diabetes and obesity appear simultaneously in a single person.

In the present invention, "ameliorating obesity" refers to suppress, reduce, and eliminate the increase in the number of adipocytes and excessive accumulation of lipids in adipocytes due to excessive adipocyte differentiation in a subject.

In the present invention, "ameliorating metabolic syndrome" refers to suppress, reduce, and eliminate metabolic syndrome caused by an increase in the number of adipocytes and excessive accumulation of lipids in adipocytes due to excessive adipocyte differentiation in a subject.

As used herein, the term “overweight-related skin damages” refers to the damages caused by the over fat-accumulation within the adipose tissue. For example, such damages may include cellulitis, striae, lymphedema, sagginess or softening and tissue fibrosis selected from keloids, scleroderma and hypertrophic scarring. In the context of the invention, the term “fat” and “lipid” have the same meaning and may be understood interchangeably. As used herein, “treating or alleviating the overweight-related skin damages” refers to suppress, reduce or eliminate the aforementioned overweight-related skin damages.

As used herein in teh context of gene regulation, the term “controlling or regulating” refers to the upregulation and/or downregulation of the expression of at least one gene.

The content of the Narcissus spp. plant extract (e.g., the extract of the aerial parts of Narcissus spp. Plant), which is contained in the above composition, may be, but is not specifically limited to, an amount of 0.00001 to 100% by weight, preferably 0.0001 to 15% by weight, and more preferably 0.001 to 15% by weight, and even more preferably 0.001 to 10% by weight, based on the total weight of the composition.

A further aspect of the invention relates to a cosmetic or pharmaceutical composition comprising: a. at least one extract of the aerial parts of Narcissus spp. of as defined above (e.g. , as an active slimming ingredient); and b. at least one further cosmetically and/or pharmaceutically acceptable ingredient other than the extract of Narcissus spp., preferably wherein the composition is a composition for topic use selected from the forms selected from the group consisting of a solution, a suspension, an emulsion, a cream, a paste, a gel, a lotion, a powder, a microcapsule, a microgranule, a soap, a surfactant- containing water, an oil, an ointment, and a spray, or wherein the composition is a food or a nutraceutical composition which is administered orally. Another aspect of the present invention relates to a method for promoting or restoring the adipose tissue homeostasis, for preventing and/or alleviating or treating the overweight- induced skin damages selected cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight-related skin by administering to a subject in need, preferably in subject’s area in need, a sufficient amount of a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant as an active slimming ingredient as defined above.

It will be understood that the definitions and preferred embodiments made in the context of the method and composition of the present invention mutatis mutandis apply to the cosmetic method of the present invention.

Another aspect of the invention relates to a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant for use for preventing and/or treating obesity or fat-related disorders, for preventing and/or alleviating or treating the overweight-related skin damages selected from cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight-related skin.

In an embodiment of the present invention, the composition (pharmaceutical) is for use for preventing and/or treating a metabolic syndrome selected from the group consisting of fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis, and lipid- related metabolic syndrome.

It will be understood that the definitions and preferred embodiments made in the context of the methoid and composition of the present invention mutatis mutandis apply to the use of the composition or to the composition for use of the present invention.

Accordingly, in a preferred embodiemnt, the method of the present invention is:

(a) for preventing and/or treating obesity or fat-related disorders, for preventing and/or alleviating or treating the overweight-related skin damages selected from cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight-related skin; and/or

(b) for preventing and/or treating a metabolic syndrome, in particular wherein the metabolic syndrome is one or more selected from the group consisting of fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis, and lipid- related metabolic syndrome.

Another aspect of the invention relates to a cosmetic use of a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant as an active ingredient for promoting or restoring the adipose tissue homeostasis, for preventing and/or alleviating or treating the overweight-induced skin damages selected from cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight-related skin.

In an embodiment of the invention, the cosmetic use comprises: preventing the lipid accumulation by regulating the adipocyte differentiation, inhibiting excessive secretion of adipocyte-derived lipids, stimulating adipocytes lipolysis, promoting the conversion of white adipocytes into brown adipocytes by increasing the expression of UCP-1 and/or TFAM, controlling the structure of the dermal extracellular matrix by controlling the expression of MMP-1 , MMP-9, collagen 1 and elastin, counteracting or preventing the tissue fibrosis by controlling the expression of MMP-1 , MMP-9, collagen 1 and elastin; counteracting or preventing the inflammation of the adipose tissue by inhibiting the secretion of IL-6, counteracting or preventing the inflammation-induced ectopic collagen-l depots formation in the adipose tissue by inhibiting the synthesis of procollagen-l by preadipocytes, controlling the secretion of adipokines from adipose tissue, and a combination of two or more thereof.

In an embodiment, the cosmetic use of the composition of the invention is characterized in that:

A. the Narcissus spp. plant is selected from the group consisting of Narcissus tazetta L, Narcissus jonquilla L, and Narcissus Pseudo-Narcissus L, preferably Narcissus jonquilla L

B. the aerial part is selected from the group consisting of the leaves, the stems, the flowers, or a combination of two or more thereof, preferably the stems and the flowers;

C. it is an aqueous, a hydroalcoholic, or an alcoholic extract, preferably an alcoholic extract, more preferably an ethanolic extract; and/or

D. the use is as defined above.

As used herein, the term "pharmaceutical composition" means a composition prepared for preventing and/or treating disease and may be formulated into various forms according to each conventional method. For example, the composition may be formulated into oral dosage forms such as discutient, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., and parenteral dosage forms such as diluents or excipients such as lubricants, wetting agents, flavoring agents, emulsifying agents, suspending agents, preservatives, surfactants, etc. In addition, it can be formulated and used in the form of external preparations, suppositories, skin external preparations, and sterile injectable solutions. As a specific example, the composition of the present invention may be used orally in an oral dosage form. As another specific example, the composition of the present invention may be used by a method such as direct application or dispersion to a area such as a thigh, buttocks, or abdomen where a large number of adipocyte are distributed. The above application and dispersion are not limited to the above area and may be applied to any area in which adipocytes are developed.

In addition, according to each formulation, a pharmaceutically acceptable carrier, such as a buffering agent, a painless agent, a solubilizing agent, an isotonic agent, a stabilizer, a base agent, and the like, may be prepared by additionally including a carrier known in the art.

As used herein, the term “pharmaceutically acceptable carrier” may refer to a carrier or a diluent that does not interfere with the biological activity and properties of an active ingredient to be injected without stimulating organisms. The type of carrier which can be used in the present invention is not particularly limited, and any pharmaceutically acceptable carrier commonly used in the art may be used. Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, etc. These may be used alone or in combination with two or more thereof. The carrier may include a non-naturally occurring carrier.

The composition of the present invention may be administered in a pharmacologically effective amount. The above pharmacologically effective amount refers to an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects. Effective dosage levels depend on the patient's health status, type of disease, severity, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and rate of excretion, duration of treatment, factors including drugs used in combination or concurrently, and other factors well known in the medical field. Specifically, it is generally 0.01 mg to 5000 mg per 1 kg of the body weight of the administered subject and may be dividedly administered once a day or several times a day at predetermined time intervals according to the judgment of a doctor or pharmacist, but is not limited thereto.

In addition, the pharmaceutical composition of the present invention may be used alone or in combination with other pharmaceutically active compounds exhibiting a prophylactic or therapeutic effect of obesity and/or metabolic diseases (equivalent designatable as disorders) or in an appropriate set.

The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. It is important to administer an amount that can achieve the maximum effect in a minimum amount without causing side effects by taking all of these factors into consideration, and it can be easily decided by a person skilled in the art.

For example, but not limited thereto, in addition to the pharmaceutical composition comprising a Narcissus spp. plant extract (e.g., an extract of the aerial parts of Narcissus spp. plant) of the present invention as an active ingredient, it can be used in combination with commonly used antiobestic agent such as locasein that acts on the central nervous system to reduce appetite through activation of the central nervous system to suppress appetite, orlistat that inhibits fat absorption as an antiobestic agent of non-central nervous system, and Liraglutide that is an analogue of GLP-1 (Glucagon-Like Peptide 1 ) as an appetite control substance, and like.

As used herein, the term “administration” refers to introducing the pharmaceutical composition of the present invention to a subject in any suitable manner, and the injection route of the composition of the present invention may be administered via oral or parenteral various routes as long as it can reach the desired tissue.

The method of administration of the pharmaceutical composition according to the present invention is not particularly limited thereto, and may be in accordance with a method commonly used in the art. As a non-limiting example of the administration method, the composition may be administered orally or parenterally. Specifically, the composition of the present invention may be used by a method such as direct application or dispersion to a area such as a thigh, buttocks, or abdomen where a large number of adipocytes are distributed.

The pharmaceutical composition according to the present invention can be prepared in various formulations according to the intended administration method.

The frequency of administration of the composition of the present invention is not particularly limited thereto, but may be administered once a day or several times by dividing the dose.

In another aspect, the present invention provides a method for preventing and/or treating lipid-related diseases (equivalent designatable as disorders) comprising administering a pharmaceutical composition containing a Narcissus spp. plant extract (e.g., an extract of the aerial parts of the Narcissus spp. plant) to a subject.

The Narcissus spp. plant extract and its preventive and therapeutic effects on obesity and metabolic diseases (equivalent designatable as disorders) are as described above.

As used herein, the term "subject" may mean all animals including humans who have or are likely to develop obesity and/or metabolic diseases (equivalent designatable as disorders). The animals may be mammals such as cattle, horses, sheep, pigs, goats, camels, antelopes, dogs, cats, etc. in need of treatment for symptoms similar to humans, but are not limited thereto. Humans are preferred. A subject in the context of the present invention may be of any age. For instance, a subject may be an adult, an adolescent, or a child, preferably an adult.

The term “controlling weight gain” may be understood in the broadest sense as having an influence on body weight and increase in weight. Preferably, controlling weight gain is reducing weight gain. In one embodiment, controlling weight gain is minimizing or (essentially) preventing weight gain. In one embodiment, controlling weight gain is reducing weight of the subject of interest. In one embodiment, controlling weight gain is having a slimming effect (i.e., serving as an active slimming ingredient). In one embodiment, controlling weight gain is preventing, ameliorating, or treating obesity and/or metabolic syndrome, and/or restoring the adipose tissue homeostasis, and/or alleviating the overweight skin damages and/or promoting the firmness of the overweight-related skin may be obtained.

The prevention and/or treatment method of the present invention may specifically include administering the composition in a pharmaceutically effective amount to a subject who has or is at risk of developing obesity and/or metabolic disease. The administration method is as described above.

The prevention may refer to any action of inhibiting or delaying the onset of obesity and/or metabolic diseases (e.g., syndrome and metabolic disorders of the adipose tissue, the overweight-related skin damages), by administering the composition for preventing and/or treating obesity and/or metabolic diseases (equivalent designatable as disorders) according to the present invention to a subject.

In addition, the treatment may refer to any action of improving or benefitting the symptoms of obesity and/or metabolic diseases (e.g., syndrome and metabolic disorders of the adipose tissue and/or the overweight-related skin damages) by administering the composition of the present invention to a subject suspected of developing obesity and/or metabolic disease. The pharmaceutical composition comprising the Narcissus spp. plant extracts is as described above.

The composition of the present invention may contain a pharmaceutically acceptable carrier, excipient or diluent in addition to the above-described active ingredients for administration. The carrier, excipient and diluent may include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl Cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

A suitable dosage of the composition of the present invention may vary depending on the condition and weight of the patient, the severity of the disease, the form of the drug, and the time, but may be appropriately selected by a person skilled in the art. Specifically, the dosage of the Narcissus spp. plant extracts may be 50 to 500 mg/Kg.

In another embodiment, the present invention provides a skin external preparation for preventing or ameliorating obesity comprising the Narcissus spp. plant extract.

The Narcissus spp. plant extract and its preventive and therapeutic effects on obesity are as described above.

The skin external preparation of the present invention can be used for the purpose of preventing and ameliorating obesity, and the skin external preparation can be generally used for areas such as thighs and buttocks in which cellulite formed by excessive adipocyte differentiation and accumulation of lipids in adipocyte is excessively distributed. It can be applied to any area in which adipocytes are developed, not limited to the above area.

The skin external preparation according to the present invention may be formulated by containing a medium or base that is acceptable cosmetically or dermatologically. These are all formulations suitable for topical application, such as solutions, gels, solids, dough anhydrous products, emulsions obtained by dispersing the oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules, the form of ionic (liposomes) and nonionic vesicle dispersant, or the form of a cream, skin, lotion, powder, ointment, spray, pack or conceal stick. It may be used in the form of a foam or an aerosol composition further containing a compressed propellant. These compositions can be prepared according to conventional methods in the art.

In addition, the skin external preparation according to the present invention includes fatty substances, organic solvents, solubilizers, thickeners, gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic Or nonionic emulsifiers, fillers, sequestrants, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles, or adjuvants commonly used in the field of cosmetics or dermatology as any other ingredients commonly used in cosmetics. The adjuvant is introduced in an amount generally used in the field of cosmetology or dermatology.

The content of Narcissus spp. plant extracts contained in the above composition is not specifically limited, but can be contained in an amount of 0.00001 to 100% by weight, preferably 0.0001 to 15 wt%, and more preferably 0.001 to 15% by weight, and even more preferably 0.001 to 10% by weight, based on the total weight of the composition.

In another embodiment, the present invention provides a food or nutraceutical composition for preventing or ameliorating obesity and/or metabolic syndrome comprising the Narcissus spp. plant extract.

The Narcissus spp. plant extract and its preventive and therapeutic effects on obesity and metabolic syndrome are as described above.

When the composition of the present invention is used as a food additive, the Narcissus spp. plant extracts may be added as it is or may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health, or therapeutic treatment) and may further include food additives acceptable for food. Since the composition of the present invention uses an extract derived from a natural product as an active ingredient, there is no problem in terms of stability, so there is no significant limitation on the amount of mixing.

The food or nutraceutic composition of the present invention may include all foods in a conventional sense and may be mixed with terms known in the art, such as functional foods and health functional foods.

As used herein, the term 'functional food" refers to a food manufactured and processed using raw materials or ingredients having functions useful for the human body according to the (Korean) Health Functional Food Act No. 6727, and the term "functional" refers to ingestion for the purpose of obtaining useful effects for health purposes such as controlling nutrients or physiological effects on the structure and function of the human body.

In addition, as used herein, the term "health functional food" refers to a food manufactured and processed using a specific ingredient as a raw material or a food manufactured and processed by extracting, concentrating, refining, mixing specific ingredients contained in food ingredients as raw materials for the purpose of health supplementation, It refers to a food designed and processed to sufficiently exert biological control functions such as biological defense, biological rhythm control, disease prevention and recovery, etc. by the above ingredients, and the health food composition can perform functions to prevent diseases (equivalent designatable as disorders) and prevent diseases (equivalent designatable as disorders), etc.

There is no limitation on the type of food or nutraceutic in which the composition of the present invention can be used for the prevention and/or amelioration of obesity and/or metabolic diseases (equivalent designatable as disorders). In addition, the composition comprising the Narcissus spp. plant extracts of the present invention as an active ingredient may be prepared by mixing suitable other auxiliary ingredients and known additives that may be contained in food according to the choice of a person skilled in the art. Examples of foods that can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, and the like. Furthermore, foods can be prepared by adding the extract and fraction thereof according to the present invention as a main component to other extracts, tea, jelly, juice, and the like.

In addition, foods that can be applied to the present invention include, for example, special nutritional foods (e.g., milk formula, infants/baby food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (e.g., ramen, noodles, etc.), health supplement foods, seasoned foods (e.g., soy sauce, soybean paste, red pepper paste, mixed sauce, etc.), sauces, sweets (e.g., snacks), dairy products (e.g., fermented milk, cheese, etc.), other processed foods, kimchi, pickles (various kimchi, pickles, etc.) ), beverages (e.g., fruit, vegetable beverages, soy milk, fermented beverages, etc.), natural seasonings (e.g., ramen soup, etc.).

The content of Narcissus spp. plant extracts contained in the above composition is not specifically limited, but can be contained in an amount of 0.00001 to 100% by weight, preferably 0.0001 to 15% by weight, more preferably 0.001 to 15% by weight, and even more preferably 0.001 to 10% by weight, based on the total weight of the composition. When the health functional food composition of the present invention is used in the form of a beverage, it may contain various sweetening agents, flavoring agents, natural carbohydrates, and the like as an additional component, as in ordinary beverages. In addition to the above, the health functional food composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agent used in carbonated beverages, etc. In addition, it may contain flesh for the manufacture of natural fruit juice, fruit juice beverage, and vegetable beverage. In another embodiment, the present invention provides a cosmetic composition for preventing or ameliorating obesity comprising a the Narcissus spp. plant extract (e.g., an extract of the aerial parts the Narcissus spp. plant). The Narcissus spp. plant extract and its preventive and therapeutic effects on obesity are as described above.

The cosmetic composition of the present invention can be used for the purpose of preventing and ameliorating obesity. The cosmetic composition can be generally used for areas such as thighs and buttocks in which cellulite formed by excessive adipocyte differentiation and accumulation of lipids in adipocyte is excessively distributed, and the cosmetic composition is not limited to the area and can be applied to any area in which adipocytes are developed.

In the present invention, the component contained in the "cosmetic composition" may include ingredients commonly used in cosmetic compositions in addition to the active ingredient. For example, it contains the conventional adjuvant such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and the carrier. The cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, pack, massage cream and spray may be formulated, but is not limited thereto. In more detail, it may be prepared in the form of a flexible lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

When the formulation of the present invention is the paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide, etc. can be used as the carrier ingredient.

When the formulation of the present invention is the solution or turbid fluid, the solvent, solubilizing agent or emulsifying agent can be utilized as a carrier ingredient, and for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-buthylglycol oil, glycerol aliphatic ester, polyethylene glycol or aliphatic ester of sorbitan, etc. can be utilized as the carrier ingredient.

When the formulation of the present invention is suspension, the liquid diluents such as water, ethanol or propylene glycol, suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, ortragacant, etc. can be utilized as the carrier ingredient.

When the formulation of the present invention is the powder or spray, the lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder can be utilized as a carrier ingredient, and in particular when it is a spray, a propellant such as chlorofluorohydrocarbon, propane/butane or dimethyl ether can be additionally included.

When the formulation of the present invention is the surfactant-containing cleansing, the aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulphosuccinic monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanoline derivative or ethoxylated glycerol fatty acid ester, etc. can be utilized as the carrier ingredient. When the cosmetic composition of the present invention is the soap, cleansing formulation containing a surfactant or cleansing formulation containing no surfactant, it may be applied to the skin and then wiped off, removed, or washed off with water. As a specific example, the soap is liquid soap, powder soap, solid soap and oil soap, the surfactant-containing cleansing formulation is a cleansing foam, cleansing water, cleansing towel and cleansing pack, and the surfactant-free cleansing formulation is a cleansing cream, cleansing lotion, cleansing water and cleansing gel, but is not limited thereto.

The content of Narcissus spp. plant extracts contained in the above composition is not specifically limited, but can be contained in an amount of 0.00001 to 100% by weight, preferably 0.0001 to 15 wt%, more preferably 0.001 to 15% by weight, and even more preferably 0.001 to 10% by weight, based on the total weight of the composition.

The above-described composition comprising the Narcissus spp. plant extract of the present invention may be considred as a natural medicinal plant as a raw material. Therefore even when used as a pharmaceutical composition, food or nutraceutical composition, skin external preparation composition or cosmetic composition, side effects may be less compared to general synthetic compounds, and so it is safely included and can be usefully used.

The present invention also refers to use of a composition comprising or consisting of at least one extract of aerial parts of a Narcissus spp. plant as an active ingredient for controlling weight gain of a subject, preferably wherein the use is conducted as described herein. It will be understood that the definitions and preferred embodiments made in the context of the method and composition of the present invention mutatis mutandis apply to the use of the present invention. The use may be any use, including a cosmetic use (also: non- pharmaceutical, non-therapeutic) or a therapeutic (also: pharmaceutical) use.

The present invention also refers to a composition comprising or consisting of at least one extract of aerial parts of a Narcissus spp. plant as an active ingredient for use in a method of controlling weight gain of a subject, in particular wherein the subject suffers from or is at risk of a disease associated with over-weight, in particular for treating or preventing obesity or metabolic syndrome, preferably wherein the method is conducted as described herein.

It will be understood that the definitions and preferred embodiments made in the context of the method and composition of the present invention mutatis mutandis apply to the composition for use of the present invention.

Advantageous Effects

The Narcissus spp. plant extract (e.g., extract of the aerial parts of Narcissus spp. plant) which is the active ingredient of the present invention is highly safe to humans without having skin irritation and cytotoxicity, and may inhibit adipocyte differentiation, reduce the number of adipocytes, and accumulation and excessive secretion of lipids, and thus may be effectively used for a pharmaceutical composition, a food or nutraceutical composition, a skin external preparation composition and a cosmetic composition for the prevention, amelioration and treatment of obesity and/or metabolic syndrome. In particular, the Narcissus spp. plant extract (e.g., extract of the aerial parts of Narcissus spp. plant) may be effectively applied for the purpose of inhibiting the accumulation and excessive secretion of lipids in areas with abundant adipocytes, including areas such as thighs, underarms, abdomen, hips and buttocks, where cellulite produced due to excessive adipocyte differentiation is excessively distributed. More generally, the extract of the aerial parts of Narcissus spp. plant of the present invention may be effective in managing the adipose tissue inflammation and homeostasis in overweight context. In addition, the extract of the aerial parts of Narcissus spp. plant may be effective in restoring the adipose tissue homeostasis.

Description of Drawings

FIG. 1 shows the results of measuring the effect of Narcissus spp. extracts according to the present invention on the inhibition of lipids accumulation in 3T3-L1 adipocytes. The results demonstrate the inhibition effect of Narcissus spp. extracts on the inhibition of the differentiation of 3T3-L1 preadipocytes into adipocytes. These results demontrate the effects of Narcissus tazetta L. extract, Narcissus Pseudo-Narcissus L extract, and Narcissus jonquilla L. extract compared to caffeine.

FIG. 2 shows the results of quantifying the effect of Naricissus spp. extracts according to the present invention on lipolysis of differentiated 3T3-L1 adipocytes. FIG. 2 demonstrates the effect of Narcissus tazetta L., Narcissus Pseudo-Narcissus L and Narcissus jonquilla L. extracts compared to caffeine. These results demonstrate the lipolytic effect of Narcissus spp. extracts.

FIG. 3 shows the results of measuring the effect of a Narcissus tazetta L., Narcissus jonquilla L. or Narcissus Pseudo-Narcissus L extract according to the present invention on the inhibition of triglycerides accumulation in 3T3-L1 adipocytes.

FIG. 4 shows the results of measuring the effect of a Narcissus jonquilla L. extract according to the present invention, in comparison to the caffeine, on the release of glycerol by 3T3-L1 adipocytes. The results demonstrate the lipolytic effect of Narcissus jonquilla L. extract that is is stronger than caffeine.

FIG. 5 shows the results of measuring the effect of a Narcissus jonquilla L. extract according to the present invention on the release of glycerol by human fully mature adipocytes. The results confirm the lipolytic effect, as demonstrated in Fig. 4, of Narcissus jonquilla L. extract on fully mature adipocytes.

FIG. 6 and 7 show the results of measuring the effect of a Narcissus jonquilla L. extract according to the present invention on the fibro-inflammation of human pre-adipocytes in inflammatory condition by quantifying IL-6 and procollagen-l releases.

FIG. 8 shows the results of measuring the effect of a Narcissus jonquilla L. extract according to the present invention on the expression of the biological markers (collagen I, Elastin, MMP-1 and MMP-9) by the immature 3T3-L1 adipocytes. These markers are important for the physiology and structure of the skin. It is known that these markers are also deregulated in a tissue fibrosis context such as keloids, scleroderma and hypertrophic scarring.

FIG. 9 shows the results of measuring the effect of a Narcissus jonquilla L. extract according to the present invention on the browning promoting effect in 3T3-L1 adipocytes by the stimulation of 2 mitochondrial markers UCP-1 and TFAM.

FIG. 10 shows the results (microscopic images) of performing Oil-red 0 staining to observe the effects of a Narcissus spp. extracts (Narcissus tazetta L, Narcissus jonquilla L. or Narcissus Pseudo-Narcissus L extract) according to one embodiment of the present invention on the inhibition of the differentiation of 3T3L1 preadipocytes into adipocytes. A-D show cell images. E-F show Oil-Red 0 staining. A and E show control (day 0-9), B and F show activity of 50 pg/mL Narcissus tazetta extract, C and G show activity of 50 pg/mL Narcissus jonquilla extract, and D and FI show activity of 50 pg/mL Narcissus Pseudo- Narcissus extract. hereinafter, the present specification will be described in detail with reference to examples to understand the present invention. However, the examples according to the present specification can be modified in various forms, and it is not to be interpreted that the scope of the present specification is limited to the examples described below. The examples of the present specification are provided to more completely explain the present invention to a person skilled in the art.

Example 1 : Production of Narcissus spp. plant extracts

An aerial part of each of Narcissus tazetta L., Narcissus jonquilla L. and Narcissus Pseudo- Narcissus L. plants was washed clean, dried in shade at 20°C to 35°C, and then pulverized to powder having a particle size of 1 mm or less. Thereafter, 100 g of the powder of the aerial part (e.g., stem, leaf, and flower) of each Narcissus spp. plant was immersed in a 70% ethanol solvent, and then subjected to ultrasonic extraction for 48 hours, and the resulting extract was filtered through filter paper (Advantec No.2). The filtrate was concentrated under reduced pressure to obtain an ethanol extract of the aerial part of each Narcissus spp. plant.

For the following examples, the Narcissus spp. extracts obtained according to the example 1 are used for all of the experiments. It could be assumed that all of the Narcissus spp. extract obtained in the example 1 may reasonably exert the effects as described in the present disclosure.

All data were expressed as mean ± standard deviations. *<0.05, **<0.01 , ***<0.001 were indicated statistically significant.

Example 2: Adipocyte differentiation inhibitory effect of Narcissus spp. plant extracts To evaluate the adipocyte differentiation inhibitory effect of each of the Narcissus spp. plant extracts, the following experiment was conducted.

Specifically, (immature) adipocytes (3T3-L1 ) purchased from ATCC (American Tissue Culture Collection, USA) were prepared and cultured in a DMEM medium containing 10% by weight BCS (Bovine Calf Serum). For differentiation into adipocytes, the (immature 3T3- L1 ) adipocytes were seeded into a 6-well plate at a density of 1 x10 ⁵ cells and then cultured in 10% by weight BCS-containing DMEM medium at 37°C under 5% CO2 until the cells reached confluence in each well. Then, the cells were further cultured for 2 days and were treated with an MDI cocktail (0.5 mM isobutylmethylxanthin, 1 mM dexamethason and 1 pg/mL insulin). After 3 days, the medium was replaced with a medium containing 1 pg/mL of insulin, and after 3 days again, was replaced with a DMEM medium containing 10% by weight FBS (fetal bovine serum). From the time point when differentiation was induced by treatment with the MDI cocktail, the cells were also treated with the test sample (Narcissus spp. extracts) or caffeine, and then retreated with the same concentration of the test sample every time the culture medium was replaced. To measure the amount of lipids accumulated in the differentiated cells, the lipids were stained by Oil Red 0 staining and dissolved with isopropyl alcohol, and then the optical density at 540 nm was measured.

As a result, as can be seen in FIG. 1 , it could be confirmed that, when immature 3T3-L1 adipocytes were treated with MDI, differentiation into adipocytes was induced and lipids were accumulated in the cells, and that the Narcissus spp. plant extracts inhibited differentiation into adipocytes in a concentration-dependent manner, so that lipids were not accumulated in the cells.

Furthermore, it was demonstrated that the inhibitory effect of Narcissus jonquilla L extract is, for example, 80 times higher than caffeine at 5 ppm for Narcissus jonquilla extract vs. 400 ppm for the caffeine for obtaining 80% of reduction of the lipids in differentiated 3T3-L1 adipocytes. Taken together, these experimental results demonstrate the efficacy of the Narcissus spp. plant extract in exerting a slimming effect and controlling the weight gain.

Example 3: Lipolysis-stimulating effect of Narcissus spp. plant extract As described in Example 2 above, immature 3T3-L1 adipocytes were treated with MDI to induce differentiation into adipocytes. After 9 days of induction of differentiation, DMEM medium containing 10% by weight FBS was treated with various concentrations of the Narcissus spp. plant extracts or caffeine. To measure the amount of lipids accumulated in the differentiated cells (3T3-L1 adipocytes), the lipids were stained by Oil Red O staining and dissolved with isopropyl alcohol, and then the optical density at 540 nm was measured and quantified.

As a result, as can be seen in FIG. 2, it could be confirmed that the Narcissus spp. plant extracts concentration-dependently stimulated the degradation of lipids accumulated in the adipocytes. Moreover, caffeine is harboring a similar effect, but only at high concentration compared to the Narcissus spp. extracts. In view of the above, it was experimentally found that Narcissus spp. extracts of the present invention can be used as an active slimming ingredient.

Example 4: Triglyceride inhibitory effect of Narcissus spp. plant extract As described in Example 2 above, immature 3T3-L1 adipocytes were treated with MDI to induce differentiation into adipocytes. Then, the amount of triglycerides produced in the cells was determined using a triglyceride determination kit (Sigma, USA).

As a result, as can be seen in FIG. 3, it could be confirmed that the amount of triglycerides in the group treated with the Narcissus spp. plant extract decreased in a concentration- dependent manner, confirming its ability to induce the slimming effect and controlling the overweight gain.

Example 5: Glycerol release stimulating effect of Narcissus jonquilla L. extract As described in Example 2 above, immature 3T3-L1 adipocytes were treated with MDI to induce differentiation into adipocytes. Then, the release of glycerol by the cells was determined using a glycerol assay kit. As a result, as can be seen in FIG. 4, it could be confirmed that the release of glycerol in the group treated with the Narcissus jonquilla L. extract increases in a concentration-dependent manner. In parallel, caffeine induces similar effect at highly concentration compared to the Narcissus jonquilla L extract, demonstrating the slimming benefit effect of the extract of Narcissus jonquila L. compared to caffeine.

Example 6: Narcissus jonquilla L. extract stimulates the lipolysis of fully mature human adipocytes

Cells were isolated from adipose tissue of an obese woman of 27-year-old, body mass index (BMI) = 33.5 kg/m ² , by collagenase digestion under gentle agitation. Adipocytes were washed with a sucrose solution and then incorporated into a peptide hydrogel. Adipocytes capsules of 25 pi were formed and cultivated in specific medium with Narcissus jonquilla L. extract for 24 h before medium collection for glycerol release evaluation. It is agreed in the art that the encapsulated fully mature adipocytes 3D model gets closer to the physiological properties of the cells and allows a suitable response to pro-lipolytic stimuli. As a result, as can be seen in FIG. 5, it could be confirmed that the release of glycerol in the group treated with the Narcissus jonquilla L. extract increases in a concentration-dependent manner, demonstrating that the extract of Narcissus jonquilla L. can be used as an active slimming ingredient

Example 7: Evaluation of the effects of the Narcissus jonquilla L. extract on fibro- inflammatory preadipocytes

Preadipocytes were isolated from human female obese adipose tissue (39-year-old,

BMI = 31.6 kg/m ² ). Preadipocytes were cultured for 24 h in 100 mI of DMEM-10% by weight Fetal Bovine Serum (FBS) in 96-well plates. To induce the preadipocytes differentiation in fibro-inflammatory environment, cells were treated with a proadipogenic cocktail including insulin, glucocorticoid, 3-isobutyl-1 -methylxanthine (IBMX), and thiazolinedione and with a pro-inflammatory cocktail consisting in activated macrophage-conditioned medium (ACMC) for 14 days. During the last 24 h of culture, the cells were replaced in fresh DMEM/F12 medium to collect cells secretions. Dexamethasone 100 nM was used as anti-inflammatory response control. All conditions were performed in triplicate. The media were changed every 2 days for 14 days.

The aforementioned model of human preadipocytes cultured in an inflammatory context, using macrophages conditioned medium (ACMC), is highly relevant, in the art, to evaluate the beneficial properties of the extract of Narcissus jonquilla L, mainly to assess its ability to reverse the deleterious effects of an inflammatory adipose tissue observed in obesity and in metabolic disorders.

As a result, as can be seen in FIGS. 6 and 7, it could be confirmed that the release of IL-6 and procollagen-l in the group treated with the Narcissus jonquilla L. extract decreases in a concentration-dependent manner. In other words, the ACMC inflammatory environment induced a high increase in IL-6 secretion compared to the differentiation control condition. The secreted IL-6 increase was partially reversed by the dexamethasone, which is a well- known anti-inflammatory molecule. The Narcissus jonquilla L. extract induced a high decrease in IL-6 secretion. This effect is better and significantly different than the dexamethasone. The ACMC inflammatory environment induced a high increase in procollagen-l secretion compared to the differentiation control condition. The dexamethasone induced a decrease in the procollagen-l secretion compared to the ACMC condition. It was demonstrated that the Narcissus jonquilla L. extract induced a higher decrease in the procollagen-l secretion. Taken together, these experimental results demonstrate that the extract of Narcissus jonquilla L. can be used for counteracting or preventing the inflammation of the adipose tissue and tissue fibrosis. Example 8: Protective effect of Narcissus jonquilla L. extract on the dermal ECM As described in Example 2 above, immature 3T3L1 adipocytes were treated with MDI with or without 50 ppm of Narcissus jonquilla L. extract to induce differentiation for 21 days into enlarged adipocytes. After 21 days of induction of differentiation, supernatants from differentiated adipocyes were collected. Basal fibroblasts were treated 48h with conditioned medium (CM) of differentiated adipocytes treated or not with Narcissus jonquilla L. extract before mRNA extraction. Then, the expression of ECM related gene level (Col1a1 , Elastin, MMP-1 , and MMP-9) were quantified using real-time PCR.

As a result, as can be seen in FIG. 8, it could be confirmed that the Narcissus jonquilla L. extract increased the expression of collagen 1 and elastin decreased by CM of enlarged adipocytes. However, Narcissus jonquilla L. extract inhibited the MMP-1 and MMP-9 expression increased by CM of enlarged adipocytes. Taken together, these results demonstrate the ability of Narcissus jonquilla extract in controlling the dermal ECM components, ameliorating the firmness and elasticity of the skin.

Example 9: Browning promoting effect of Narcissus jonquilla L. extract As described in example 2 above, immature 3T3-L1 adipocytes were treated with MDI to induce differentiation into adipocytes. After 9 days of induction of differentiation, DMEM medium containing 10% by weight FBS was treated with various concentrations of Narcissus Jonquilla extract. To measure the expression of UCP-1 and TFAM, real-time PCR was used for quantification of mRNA levels. As a result, as can be seen in FIG. 9, it could be confirmed that the Narcissus jonquilla L. extract upregulated the UCP-1 and TFAM mRNA expression level in the adipocytes. Taken together, these results demonstrate the ability of Narcissus jonquilla L. extract as a slimming ingredient.

Example 10: Test for identifying the safety of Narcissus spp. plant extract to the human skin 10 1

Preparation of skin external formulation containing Narcissus spp. extract To identify as to whether Narcissus spp. plant extract, which is proven to be excellent in inhibiting the adipocyte's lipid production as described above, is safe or not for human skin, skin external formulations containing Narcissus spp. plant extract were prepared, and then a skin safety verification test was carried out.

Skin external formulation containing Narcissus spp. plant extract was prepared by the formulations in Table 1 below.

For skin external formulation, purified water, glycerin, and butylene glycol were mixed and dissolved at a temperature of 70°C (aqueous phase). The remaining components except for the above three components and trimethanolamine were dissolved at a temperature of 70°C (oil phase). The oil phase was added to the aqueous phase and stirred with a homomixer (Tokushu Kika, Japan) to prepare an emulsion, and trimethanolamine was added thereto. Then, bubbles produced in the mixture were removed, after which the mixture cooled to room temperature, thereby preparing the skin external formulation. Table 1

10-2. Cumulative irritation test

Each of the skin external formulations prepared in Example 10-1 above was applied every other day to the forearms of 30 healthy adults and allowed to stand for 24 hours. The test was repeated so that each subject was treated with 9 fresh patches in total, so as to confirm whether Narcissus spp. plant extract irritates the skin.

As a patch method, Finn chamber (Epitest Ltd, Finland) was used. After loading each of the above skin external formulations of 15ul each into the chamber, the patch was carried out. The level of reaction each time on the skin was graded using the following empirical formula 1 , and the result was shown in the following Table 2 Empirical formula 1

Average response degree = [[Response index X Response degree / Total number of subjects X Highest score (4 points)] X 100] / Number of examinations Regarding the response degree, 1 point was provided for ±, 2 points for +, and 4 points for ++. When the average response degree was less than 3, the composition was determined to be safe for use on the skin.

Table 2

As a result of Table 2, in the test group, the subjects corresponding to ±, +, and ++ numbered 1 , 0 and 0, respectively, and no skin response appeared. As a result of calculating the [(1 X2)/(20X4)]X100/9=0.13, the mean reaction degree for the Test group is 0.13, test group is all less than 3, suggesting that the composition of the present invention is safe for use on human skin.

As described in Table 2 above, external skin formulation containing Narcissus spp. plant extract (test groups) did not show any apparent cumulative irritation and were determined to be safe for human skin.

Formulation Example 1 : Cosmetic formulations Formulation Example 1 -1. Preparation of skin softener

As shown in Table 3 below, a skin softener containing Narcissus spp. plant extract as an active ingredient was prepared according to a conventional method.

Table 3

Formulation Example 1-2. Preparation of nourishing softener

As shown in Table 4 below, a nourishing softener containing Narcissus spp. plant extract as an active ingredient was prepared according to a conventional method. Table 4

Formulation Example 1-3. Preparation of nourishing cream

As shown in Table 5 below, a nourishing cream containing Narcissus spp. plant extract as an active ingredient was prepared according to a conventional method.

Table 5

Formulation Example 1-4. Preparation of massage cream

As shown in Table 6 below, a massage cream containing Narcissus spp. plant extract as an active ingredient was prepared according to a conventional method.

Table 6 Formulation Example 1-5: Preparation of pack

As shown in Table 7 below, a pack containing Narcissus spp. plant extract as an active ingredient was prepared according to a conventional method.

Table 7

Preparation Example 2: Preparation of pharmaceutical formulations Preparation Example 2-1 : Preparation of powder formulation

Table 8

The above components were mixed and filled into a sealed bag to produce a powder formulation. Preparation Example 2-2: Preparation of tablet formulation

Table 9 The above components were mixed and then compressed to a tablet according to a conventional method.

Preparation Example 2-3. Capsule formulation

Table 10

The above components were mixed and then filled into a gelatin capsule to a conventional method.

Preparation Example 24 gel formulation Table 11

The above components were mixed, and a gel containing Narcissus spp. plant extract as an active ingredient was prepared according to a conventional method.

Preparation Example 2-5. Ointment production

Table 12

Preparation Example 3: Preparation of Food

Preparation Example 3-1 : Preparation of Flour Food The Narcissus spp. plant extract of the present invention was added 0.5 to 5.0 parts by weight to flour, and the mixture prepared bread, the mixture prepared cakes, cookies, crackers, and noodles.

Preparation Example 3-2: Preparation of Soup and Gravies 0.1 to 5.0 parts by weight of Narcissus spp. plant extract of the present invention were added to soup and gravies, and then meat products, noodle soup, and gravies for health promotion were prepared.

Preparation Example 3-3: Preparation of Ground Beef

10 parts by weight of Narcissus spp. plant extract of the present invention were added to ground beef to prepare to ground beef for health promotion.

Preparation Example 3-4: Preparation of Dairy Products

5 to 10 parts by weight of Narcissus spp. plant extract of the present invention were added to milk, and various dairy products, such as butter and ice cream, were prepared using the milk

Preparation Example 3-5: Preparation of Sausage

As shown below, sausage food products containing Narcissus spp. plant extract of the present invention were manufactured. Pork 65.18w%, chicken 25% by weight, starch 3.5% by weight, soybean protein 1.7% by weight, table salt 1.62% by weight, glucose 1.4% by weight, glycerin 1.5% by weight, and Narcissus spp. plant extract 0.1 % by weight of the present invention were mixed to prepare sausages according to a conventional method.

Preparation Example 3-6: Preparation of healthy beverages The supplementary ingredients were homogeneously mixed with 5 g of Narcissus spp. plant extract of the present invention. The above supplementary ingredients are such as high fructose corn syrup (0.5% by weight), oligosaccharide (2% by weight), sugar (2% by weight), edible salt (0.5% by weight), and water (75% by weight). After flash pasteurization, the healthy beverage was prepared by packaging in a small packaging container such as a glass bottle, plastic bottle, etc.

Preparation Example 3-7: Preparation of vegetable juice

Vegetable juice was prepared by adding 5 g of Narcissus spp. plant extract of the present invention to 1 ,000 ml_ of tomato or carrot juice.

Preparation Example 3-8: Preparation of fruit juice

Fruit juice was prepared by adding 1 g of Narcissus spp. plant extract of the present invention to 1 ,000 ml_ of apple or grape juice.

Further embodiments of the present invention refer to the following:

[Embodiment 1 ]

A pharmaceutical composition for preventing or treating obesity or metabolic syndrome comprising, as an active ingredient, at least one Narcissus spp. plant extract selected from the group consisting of a Narcissus tazetta L. extract, a Narcissus jonquilla L. extract and a Narcissus Pseudo-Narcissus L. extract. [Embodiment 2]

The pharmaceutical composition of embodiment 1 , wherein the metabolic syndrome is one or more selected from the group consisting of fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis, and lipid-related metabolic syndrome. [Embodiment s]

A food composition for preventing or ameliorating obesity or metabolic syndrome comprising a Narcissus spp. plant extract as an active ingredient.

[Embodiment 4] The food composition of embodiment 3, wherein the metabolic syndrome is one or more selected from the group consisting of fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis, and lipid-related metabolic syndrome.

[Embodiment s] A skin external preparation composition for preventing or ameliorating obesity comprising a Narcissus spp. plant extract as an active ingredient.

[Embodiment s]

The skin external preparation composition of embodiment 5, which is applied to a subject’s area having cellulite formed due to excessive adipocyte differentiation and accumulation of lipids in adipocytes.

[Embodiment /]

A cosmetic composition for preventing or ameliorating obesity comprising a Narcissus spp. plant extract as an active ingredient.

[Embodiment s]

The cosmetic composition of embodiment 7, which is applied to a subject’s area having cellulite formed due to excessive adipocyte differentiation and accumulation of lipids in adipocytes.

[Embodiment 9]

Composition comprising or consisting of at least one extract of the aerial parts of Narcissus spp. plant as an active slimming ingredient.

[Embodiment 10]

Use of a composition comprising or consisting of at least one extract of the aerial parts of Narcissus spp. plant as an active slimming ingredient.

[Embodiment 11 ]

Composition according to embodiment 9 or use according to embodiment 10, wherein the Narcissus spp. plant is selected from the group consisting of Narcissus tazetta L, Narcissus jonquilla L., and Narcissus Pseudo-Narcissus L. [Embodiment 12]

Composition according to embodiment 9 or 11 or use according to embodiment 10 or 11 , wherein the aerial part is selected from the group consisting of the leaves, the stems, the flowers, or a combination of two or more thereof.

[Embodiment 13]

Composition according to any of embodiments 9, 11 or 12 or use according to any of embodiments 10 to 12, wherein the Narcissus spp. plant is Narcissus jonquilla L.

[Embodiment 14]

Composition according to any of embodiments 9, 11 to 13 or use according to any of embodiments 10 to 13, wherein the at least one extract of the aerial parts of Narcissus spp. is characterized in that:

(i) it is an aqueous, a hydroalcoholic, or an alcoholic extract; and/or

(ii) it comprises at least 0.05% by weight, preferably at least 0.1 % by weight, more preferably at least 0.15% by weight, particularly at least 0.2% by weight of dry matter, referred to the total weight of the extract.

[Embodiment 15]

Composition according to any of embodiments 9, 11 to 14 or use according to any of embodiments 10 to 14, wherein the alcohol is selected from the group consisting of ethanol, methanol, propanol, butanol, pentanol, phenol, glycerol, 1,3-butylene glycol, propane diol, or a mixture of two or more thereof.

[Embodiment 16] Composition according to any of embodiments 9, 11 to 15 or use according to any of embodiments 10 to 15, wherein the composition comprises 0.0001 to 15% by weight, preferably 0.001 to 15% by weight, more preferably 0.001 to 10% by weight, based on the total weight of the composition.

[Embodiment 17]

A cosmetic or pharmaceutical composition comprising: a. at least one extract of the aerial parts of Narcissus spp. as defined in any one of embodiments 9 to 16 as an active slimming ingredient; and b. at least one further cosmetically and/or pharmaceutically acceptable ingredient other than the extract of Narcissus spp., preferably wherein the composition is a composition for topic use selected from the group consisting of a solution, a suspension, an emulsion, a cream, a paste, a gel, a lotion, a powder, a microcapsule, a microgranule, a soap, a surfactant-containing water, an oil, an ointment, and a spray, or wherein the composition is a food or a nutraceutical composition which is administered orally.

[Embodiment 18]

A composition as defined in any of the embodiments 9 to 17 for use for preventing and/or treating obesity or fat-related disorders, for preventing and/or alleviating or treating the overweight-related skin damages selected from cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight-related skin. [Embodiment 19]

A composition as defined in any of the embodiments 9 to 18 for use for preventing and/or treating a metabolic syndrome. [Embodiment 20]

A composition for use according to embodiment 19, wherein the metabolic syndrome is one or more selected from the group consisting of fatty liver, type 2 diabetes, hyperlipidemia, cardiovascular disease, arteriosclerosis, and lipid-related metabolic syndrome.

[Embodiment 21 ]

Cosmetic use of a composition comprising or consisting of at least one extract of the aerial parts of Narcissus spp. plant as an active ingredient for promoting or restoring the adipose tissue homeostasis, for preventing and/or alleviating or treating the overweight-induced skin damages selected from cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight-related skin.

[Embodiment 22]

The cosmetic use according to embodiment 21 , wherein the cosmetic use comprises: - preventing the lipid accumulation by regulating the adipocyte differentiation, inhibiting excessive secretion of adipocyte-derived lipids, stimulating adipocytes lipolysis, promoting the conversion of white adipocytes into brown adipocytes by increasing the expression of UCP-1 and/or TFAM, controlling the structure of the dermal extracellular matrix by controlling the expression of MMP-1 , MMP-9, collagen 1 and elastin, counteracting or preventing the tissue fibrosis by controlling the expression of MMP-1 , MMP-9, collagen 1 and elastin; counteracting or preventing the inflammation of the adipose tissue by inhibiting the secretion of IL-6, counteracting or preventing the inflammation-induced ectopic collagen I depots formation in the adipose tissue by inhibiting the synthesis of procollagen-l; controlling the secretion of adipokines from adipose tissue, and a combination of two or more thereof.

[Embodiment 23]

The cosmetic use according to any of embodiments 21 or 22, wherein

A. the Narcissus spp. plant is selected from the group consisting of Narcissus tazetta L, Narcissus jonquilla L, and Narcissus Pseudo-Narcissus L, preferably Narcissus jonquilla L

B. the aerial part is selected from the leaves, the stems, the flowers, or a combination of two or more thereof, preferably the stems and flowers;

C. it is an aqueous, a hydroalcoholic, or an alcoholic extract, preferably alcoholic extract, more preferably ethanolic extract; and/or

D. the use is as defined in any of embodiments 21 or 22.

[Embodiment 24]

A cosmetic method for promoting or restoring the adipose tissue homeostasis, for preventing and/or alleviating or treating the overweight-induced skin damages selected from cellulites, lymphedema, striae and tissue fibrosis, and/or for promoting the firmness and the texture of the overweight-related skin by administering to a subject in need, preferably in subject’s area in need, a sufficient amount of a composition comprising (or consisting of) at least one extract of the aerial parts of Narcissus spp. plant as an active slimming ingredient as defined in any of the embodiments 9 to 17.