TW201803583A - Plant-based compositions for weight management and methods of use - Google Patents

Abstract

Compositions and methods for preventing or treating obesity are described. Compositions include an extract of green tea, an extract of Gynostemma, and optionally, an extract of unripe apple, wherein the extract of green tea and the extract of Gynostemma synergistically inhibit the activity of Sterol Regulatory Element Binding Protein 1c (SREBP1c) promoter, and wherein the extract of green tea, the extract of Gynostemma, and the extract of unripe apple inhibit IL-1beta stimulated Nuclear Factor Kappa-Light-Chain-enhancer of activated B cells (NF-[kappa]B) activity.

Description

Plant-based composition for weight management and method of use

RELATED APPLICATIONS This patent is based on 35 USC § 119(e) claiming the benefit of the filing date of US Provisional Patent Application No. 62/357,586, filed on July 1, 2016, which is hereby incorporated by reference. For reference.

The present invention relates to plant-based compositions and methods of use for weight management.

BACKGROUND OF THE INVENTION In view of the prevalence of increased human obesity or unwanted weight gain worldwide, there is an urgent need for an effective pharmacological approach to preventing obesity and/or its effects at early stages and/or treating it. In obesity, destructive complications are an increased incidence of type 2 diabetes, of which 60% can be directly attributed to an increase in body fat.

In the past decade, obesity has been recognized as an inflammatory disease characterized by a chronic, low-grade inflammatory state. Obesity is associated with increased circulating concentrations of inflammatory interleukins and acute phase proteins. Local up-regulation of genes encoding inflammatory factors has been described, which is associated with a significant accumulation of macrophages in adipose tissue. Furthermore, visceral adipose tissue in an obese state is characterized by a higher expression of anterior-inflammatory mediators and an increased accumulation of macrophages. Since visceral fat is directly discharged to the liver via the portal vein, inflammation of visceral adipose tissue can have an adverse effect on glucose and lipid liver metabolism, that is, increased hepatic sugar and lipid storage and increased glucose output.

The energy balance in the human body is regulated by shuttle carbon (carbohydrate and lipid) towards storage or utilization. The distribution of carbon between carbohydrates and lipids is highly integrated and transcriptionally controlled.

Novel and effective pharmacological approaches to prevent obesity and/or its effects at an early stage are needed.

SUMMARY OF THE INVENTION Certain specific examples relate to a composition comprising an extract of green tea, an extract of Gynostemma , and an extract of an immature apple, wherein the extract of green tea and the Gynostemma pentaphyllum The extract of the genus synergistically inhibits the activity of the Sterol Regulatory Element Binding Protein 1c (SREBP1c) promoter, wherein the extract of the green tea, the extract of the genus Gynostemma and the extraction of the immature apple Inhibiting nuclear factor-activated nuclear factor Kappa-Light-Chain-enhancer of activated B cells (NF-κB) activity, the composition exhibiting at least an IC50 of at least 50% Inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Some other specific examples relate to a composition comprising an extract of green tea and an extract of the genus Gynostemma, wherein the extract of the green tea and the extract of the genus Gynostemma synergistically inhibit the activity of the SREBP1c promoter, the composition At least an IC50 is exhibited, wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Some further specific examples relate to a composition comprising an extract of green tea, an extract of the genus Gynostemma, and an extract of an immature apple, wherein the extract of the green tea, the extract of the genus Gynostemma, and the The extract of the immature apple inhibits IL-1β-stimulated NF-κB activity, the composition exhibiting at least an IC50, wherein at least 50% inhibition occurs in each extract from about 0.1 μg/mL to about 1000 μg/mL concentration.

In such described compositions, the total amount of such extracts can be between about 0.005 weight percent and about 50 weight percent; or between about 0.0033 weight percent and about 33.3 weight percent. The composition may be in a form suitable for oral ingestion, such as a pill, a lozenge, a capsule, a caplet, a sugar lozenge, a powder, a liquid, a gel, a syrup, A slurry, a suspension, a supplement (ie, a nutritional supplement). The composition can be a pharmaceutical drug or supplement, an over-the-counter drug or supplement, or a food product or supplement. The composition can be used to treat or prevent obesity. The composition can include at least one of a pharmaceutically or nutraceutically acceptable carrier, adjuvant or excipient.

Some further specific embodiments relate to a method for treating or preventing obesity in a subject comprising administering to the individual a sufficient amount of an extract containing a green tea, an extract of Gynostemma, and an alternative a composition of an immature apple extract that exhibits at least an IC50, wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL, and wherein The composition reduces the weight of the individual by at least 5%. The green tea extract and the Gynostemma extract synergistically inhibit the activity of the SREBP1c promoter. The green tea extract, the Gynostemma extract and the extract of the immature apple inhibit IL-1β-stimulated NF-κB activity.

Some further specific embodiments relate to a method for inhibiting the activity of a SREBP1c promoter in a body comprising administering to the individual a sufficient amount of an extract comprising a green tea and an extract of the genus Gynostemma a composition wherein the extract of green tea and the extract of the genus Gynostemma synergistically inhibit the activity of the SREBP1c promoter, and wherein the composition exhibits at least an IC50, wherein at least 50% inhibition occurs from about 0.1 μg/mL to about Concentration of 1000 μg/mL.

Still further specific embodiments relate to a method for inhibiting IL-1β-stimulated NF-κB activity in a body comprising administering to the individual a sufficient amount of an extract comprising a green tea, An extract of Gynostemma and an extract of an immature apple, wherein the extract of green tea, the extract of Gynostemma and the extract of the immature apple inhibit IL-1β-stimulated NF- κB activity, the composition exhibits at least an IC50, wherein at least 50% inhibition occurs at a concentration of from about 0.1 μg/mL to about 1000 μg/mL.

In the methods described, the administration is accomplished to treat or prevent at least one of sugar addiction, unwanted weight gain, obesity, or metabolic syndrome. The individual is at risk of being obese or obese. The administered composition may be in a form suitable for oral ingestion, such as a pill, a lozenge, a capsule, a capsule tablet, a sugar lozenge, a powder, a liquid, a gel, a syrup , a slurry, a suspension, a supplement. The administered composition can be a pharmaceutically acceptable drug. The administered composition can be an over-the-counter drug. The administered composition can be in a food product.

These and other features and advantages of the present invention will become apparent from the <RTIgt;

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS It is to be understood that the compositions and methods described are not limited to the particular compositions, methodology, or procedures described herein. Further, all of the technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art, unless otherwise defined. It is also to be understood that the terminology used herein is for the purpose of describing the particular embodiments, and is not intended to limit the scope of the invention. In certain embodiments, a sterol regulatory element binding protein 1c (SREBP1c) promoter inhibitor can be administered to a subject to inhibit SREBP1c promoter activity in the body. SREBP1c is a transcription factor found to control denovo lipogeneic pathways (i.e., lipid formation from carbohydrate sources). SREBP1c is particularly important for transcriptionally regulating the flux of carbohydrates towards fatty acid and triglyceride synthesis during periods of excessive carbohydrate uptake, which is a common episode that causes overweight and obesity. Surprisingly, as shown herein, a blend of botanical ingredients or plant extracts of green tea and Gynostemma provides a synergistic inhibition of the activity of a SREBP1c promoter inhibitor. Without being bound by one theory, the utility of the SREBP1c promoter activity is not due to the separate green tea or Gynostemma extract, but only when the two are combined into a composition. Therefore, it is believed that the combination of "all" botanical compounds in these two extracts contributes to the synergistic inhibition of the activity of a SREBP1c promoter inhibitor. This inhibition of SREBP1c promoter activity is effective in preventing and/or reducing lipid formation from carbohydrate sources in the body. Carbohydrates present in the body may be derived from sugars, such as fructose-containing sugars (eg, fructose, sucrose, or high fructose corn syrup), sugars that can be converted into fruit sugars in the body (eg, sorbitol), glucose, Carbohydrates (eg, starch) or any other source. Enhanced flux of carbohydrate towards fatty acid and triglyceride synthesis and SREBP1c promoter activity during excessive carbohydrate uptake can contribute to a variety of different conditions (eg, obesity, metabolic syndrome, kidney disease, pre-diabetes, diabetes, adenosine triphosphate ( ATP) consumption, monocyte chemotactic protein-1 (MCP-1) production, insulin resistance or intrarenal uric acid production). Inhibition of SREBP1c promoter activity can be beneficial for supporting weight management (eg, by transcriptionally modulating the flux of carbohydrates toward fatty acid and triglyceride synthesis during excess carbohydrate uptake and associated caloric intake) and Providing an effective pharmacological means of preventing obesity and/or acting on it at an early stage and/or treating it.

Inhibition of SREBP1c promoter activity is effective in reducing lipid formation from carbohydrate sources (which may contribute to overweight, obesity, metabolic syndrome or other conditions). Reducing lipid formation from carbohydrate sources can be beneficial for supporting weight management (e.g., by transcriptionally modulating the flux of carbohydrates toward fatty acid and triglyceride synthesis).

In certain other embodiments, a nuclear factor-activating B cell kappa light chain enhancer (NF-κB) inhibitor can be administered to a body to inhibit IL-1β-stimulated NF-κB activity in the body. NF-κB is a transcriptional regulator of pro-inflammatory genes that have been found to be elevated in obesity. Surprisingly, a blend of botanical ingredients or plant extracts of green tea, Gynostemma and immature apples provides an inhibition of IL-1β-stimulated NF-κB activity. This inhibition of IL-1β-stimulated NF-κB activity is effective in preventing and or reducing pre-inflammatory cytokines (which are also known to contribute to a variety of different conditions, such as anterior-inflammation characterized by being characterized in the body Increased expression of interleukins in the performance of chronic low-grade inflammatory conditions overweight and obesity). Inhibition of IL-1β-stimulated NF-κB activity in the body may be advantageous for supporting weight management (eg, by reducing the expression of pro-inflammatory cytokines) and providing a prevention of obesity and/or at an early stage The effective pharmacological approach to action and/or treatment.

The terms "individual" and "patient" as used interchangeably herein mean a mammal, particularly a human that has previously been diagnosed. In a particular embodiment, the individual is an individual at risk of obesity or an obese individual.

The term "obesity" means a condition characterized by an excess of body fat. The definition of obesity is based on the Body Mass Index (BMI), which is calculated as the body weight per square foot (in meters) (kg/m ² ). By obesity is meant a condition in which an otherwise healthy individual has a BMI greater than or equal to 30 kg/m ² , or an individual having at least one complication having a BMI greater than or equal to 27 kg/m. ² conditions.

An "obese individual" is an individual having a BMI greater than or equal to 30 kg/m ² of other aspects of health or an individual having a BMI greater than or equal to 27 kg/m ² with at least one complication. A "person at risk of obesity" is an otherwise healthy individual having a BMI of 25 kg/m ² to less than 30 kg/m ² or a one having a weight of 25 kg/m ² to less than 27 kg/m ² The BMI has at least one comorbid individual. In the Asian population, the increased risk associated with obesity can occur at a lower BMI. In Asia and Asia-Pacific countries (including Japan), "obesity" means an individual having an obesity-induced or obesity-related complication that has at least one that requires weight loss or is improved by weight loss. A condition in which the BMI is greater than or equal to 25 kg/m ² . An "obese individual" in these countries means an individual having at least one obesity-induced or obesity-related complication that requires weight loss or improved by weight loss has a BMI greater than or equal to 25 kg/ m ² . In these countries, a "person at risk of obesity" is a person having a BMI of greater than 23 kg/m ² to less than 25 kg/m ² .

The term "sterol regulatory element binding protein 1c" or "SREBP1c" as used herein has its ordinary meaning in the art. SREBP1c is a transcription factor that controls the re-lipidogenesis pathway (ie, lipid formation from carbohydrate sources). SREBP1c is particularly important for transcriptionally regulating the flux of carbohydrates toward fatty acid and triglyceride synthesis during excess carbohydrate intake, which is a common episode that causes overweight and obesity.

"Nuclear factor-activating B cell kappa light chain enhancer" or "NF-κB" as used herein has its general meaning in the art. NF-κB is a transcriptional regulator of the pro-inflammatory gene that is elevated in obesity.

The term "inhibitor of SREBP1c activity", "inhibitor of SREBP1c activity" or "inhibitor of SREBP1c promoter activity" means a pure compound, composition having a biological effect of inhibiting or significantly reducing the activity of the SREBP1c promoter, Extract, botanical extract, extract mixture, botanical extract mixture, components of the extract and/or active agent or ingredient or a combination thereof.

The term "IL-1β-stimulated NF-κB inhibitor" or "IL-1β-stimulated NF-κB activity inhibitor" or "IL-1β-stimulated NF-κB activity inhibitor" means having one Pure compounds, compositions, extracts, botanical extracts, extract mixtures, botanical extract mixtures, components of the extract that are biologically effective to inhibit or significantly reduce the activity of IL-1β-stimulated NF-κB And/or an active agent or ingredient or a combination thereof.

The term "composition" means a treatment, amelioration, promotion, addition, management, control, maintenance, optimization, modification, reduction, inhibition or prevention of a particular condition associated with a natural state, biological process or disease or condition. product. For example, the described composition modulates or reduces obesity and the like in an obese individual or an individual at risk of obesity. The term composition includes, but is not limited to, a pharmaceutical (ie, drug), over-the-counter comprising an effective amount of an extract (s), at least one component thereof, or a mixture or mixture thereof. (OTC), cosmetics, food, food ingredients or dietary supplements.

As used herein, the term "extract," "plant extract," or "botanical extract" means a plant (including green tea, Gynostemma, and immature) in a concentrated form. An active ingredient of a substance, a solid, a viscous or liquid substance or a form of a pure compound, a composition, an extract, a botanical extract, an extract mixture, a botanical extract a mixture of substances, a component of the extract and/or an active agent or ingredient or a combination thereof. The term "extract" is intended to include not only one by using a lower alcohol selected from water, 1 to 4 carbon atoms (such as methanol, ethanol, butanol, etc.), ethylene, acetone, hexane, ether, Chloroform, ethyl acetate, butyl acetate, dichloromethane, N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), 1,3-butyl A solvent derived from the diol, propylene glycol, and a combination thereof, a crude extract produced from green tea, Gynostemma, and immature apples, and a separate portion of the crude extract in the solvent. Any extraction method can be employed (some exemplary methods are provided below) as long as it ensures extraction and storage of the active ingredient(s). Examples of botanical extracts include extracts from green tea, Gynostemma, and immature apples. Extracts of such green tea, Gynostemma and immature apples are also commercially available from a variety of sources.

The term "pharmaceutically acceptable" means those which are suitable for use in contact with human and lower animal tissues without undue toxicity, incompatibility, restlessness, irritation and similar properties, and a reasonable benefit/risk ratio. A commensurate drug, drug, extract or inert ingredient.

The terms "administer", "administered", "administers" and "administering" are defined as the import or supply of a composition to a body to perform its intended Features. Administration can be carried out by any suitable route, such as orally, intranasally, parenterally (intravenously, intramuscularly, intraperitoneally or subcutaneously), rectally or topically.

As used herein, the term "effective amount" or "therapeutically effective amount" means an amount during a period in which the dosage is effective and which is sufficient to achieve a desired result. For example, an "effective amount" or "therapeutically effective amount" means that when administered to a body (eg, a mammal (such as a human)) is sufficient to achieve treatment (such as reducing weight or reducing obesity and the like in one body) An amount of a pure composition, an extract, a botanical extract, an extract mixture, a botanical extract mixture, a component of the extract, and/or an active agent or ingredient, or a combination thereof. A disclosed composition, extract, botanical extract, extract mixture, botanical extract mixture, components and/or active agents of the extract, or an "effective amount" or "therapeutically effective treatment" The amount of the ingredient will vary depending on the active agent or the compound, the condition to be treated and its severity, the mode of administration, the duration of treatment, or the age of the individual to be treated, but may be Those skilled in the art are routinely determined by considering his own knowledge and this disclosure.

The terms "reduce", "reducing", "inhibit" or "inhibiting" mean a botanical ingredient or plant extract of green tea, Gynostemma and immature apples or these In the presence of a combination of plant extracts, a decrease or decrease in gene or protein activity and/or performance and/or its downstream effects. The inhibition can be synergistic or additive or predictive. The term "synergistic" means the interaction of extracts that, when combined, produces a total utility that is greater than the sum of individual extracts (i.e., predicted reactions), contributions, etc.; synergy.

The term "reducing obesity" indicates a measurable decrease in the body weight of an individual during or after administration of the described compositions. For example, the weight of one body can be reduced from about 5% to about 60% or more. The weight of a body can be reduced by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60% or more. It is to be understood that the percentage between the exemplary percentages exemplified above is also included.

As used herein, the term "carrier" means a composition that helps maintain one or more plant extracts in a soluble and homogeneous state in a form suitable for administration, which is non-toxic and not Interact with other components in a detrimental manner.

All quoted proportions and percentages throughout this disclosure are by weight unless otherwise indicated.

In one example, a composition for inhibiting the activity of the SREBP1c promoter may comprise a blend of an extract of green tea and an extract of the genus Gynostemma, wherein the extract of the green tea and the extract of the genus Gynostemma The activity of the SREBP1c promoter is synergistically inhibited; the composition exhibits at least an IC50, wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

In another example, a composition for inhibiting IL-1β-stimulated NF-κB activity comprises a blend of an extract of green tea, an extract of Gynostemma, and an extract of an immature apple. , wherein the extract of green tea, the extract of the genus Gynostemma, and the extract of the immature apple inhibit IL-1β-stimulated NF-κB activity, the composition exhibiting at least an IC50, wherein at least 50% inhibition occurs in one The concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Extracts of such green tea, Gynostemma and immature apples can be obtained using any suitable extraction technique. In general, any part of a plant can be used to produce the plant extract including, but not limited to, roots, stems, leaves, flowers, fruits, and pods. One or more portions of the plant can be extracted to produce the plant extract. In this aspect, one or more portions of the plant can be collected and ground. Thereafter, the ground material can be extracted with a suitable solvent. The solvent can be removed in a concentration step. For example, the extracted material can be screened or filtered to produce a supernatant and a filter cake. The filter cake can be extruded to remove a substantial portion of the liquid which can be added to the supernatant. The filter cake can then be dehydrated and used as a source of fiber. The supernatant can be distilled to remove the solvent or a portion thereof to form a botanical extract liquid concentrate. The removed solvent can be recycled. The concentrate can be dried (e.g., by spray drying) to provide a dried plant extract. The dried plant extract can be analyzed and/or standardized as described herein.

The solvent can include alcohol, water, or a combination thereof. Exemplary alcohol solvents can include, but are not limited to, C1-C7 alcohols (eg, methanol, ethanol, propanol, isopropanol, and butanol), hydro-alcohols, or mixtures of alcohols and water (eg, aqueous Hydroethanol, polyols (eg, propylene glycol and butylene glycol), and fatty alcohols. Any of these alcohol solvents may be used in the form of a mixture. In one example, the plant extract is extracted using ethanol, water, or a combination thereof (eg, a mixture of about 95% ethanol and about 5% water).

In one example, the extract of green tea, Gynostemma, and immature apples can be obtained using an organic solvent extraction technique. In another example, continuous fractional distillation of the solvent can be used to obtain the extract(s). A full water-ethanol extraction technique can also be used to obtain the extract(s). In general, this is meant to be a lump-sum extraction. The plant extract produced in the process may comprise a wide variety of different botanical compounds present in the material being extracted. These vegetable compounds may be fat-soluble or water-soluble. After collecting the extraction solution, the solvent can be evaporated to cause the extract.

Total ethanol extraction can also be used to obtain these extracts. This technique uses ethanol as a solvent. This extraction technique produces a plant extract comprising a fat-soluble and/or lipophilic compound in addition to a water-soluble compound.

Another example of an extraction technique that can be used to obtain extracts of such green tea, Gynostemma, and immature apples is Supercritical Fluid Carbon Dioxide Extraction (SFE). In this extraction procedure, the material to be extracted may not be exposed to any organic solvent. Conversely, under supercritical conditions (>31.3 ° C and > 73.8 bar), carbon dioxide can be used as the extraction solvent (with or without a modifier). Those skilled in the art will appreciate that temperature and pressure conditions can be varied to achieve optimal yields of the extract. This technique produces an extract of a fat-soluble and/or lipophilic compound similar to a per-hexane and ethyl acetate extraction technique.

The plant extract can be normalized to a specified amount of a particular compound. For example, the plant extract can be standardized to a defined amount of an active ingredient or a botanical compound. For example, the green tea plant extract can be standardized to about 40% epigallocatechin gallate (EGCG), ≥ 70% catechins, and 6%-13%. caffeine.

The amount of plant extract present in the described SREBP1c promoter activity-inhibition and or in the IL-1β-stimulated NF-κB activity-inhibiting composition may depend on several factors, including the desired inhibition Level, level of inhibition of a particular plant extract or its components, and other factors. Preferably, if the two extracts are present, each plant extract may be present in an amount from about 0.005 weight percent to about 50 weight percent, based on the weight of the total composition, if three extracts are present, each The plant extract may be present in an amount from about 0.0033 weight percent to about 33.3 weight percent, based on the weight of the total composition.

green tea

Green tea is made from the leaves of Camellia sinensis . Several varieties of green tea exist, which can vary substantially depending on growth conditions, horticulture, production processing, and harvest time. Two major varieties were planted: the Chinese lobular species ( Camellia sinensis var. sinensis ) and the Assam species ( Camellia sinensis var. assamica ). The term "extract of green tea" means a pure compound, a composition, an extract, a botanical extract, an extract mixture, a botanical extract mixture in the form of a solid, a viscous or liquid substance or preparation. A component of the extract and/or an active agent or component or a combination thereof. The substance or preparation may comprise an active ingredient (a) of a substance of any known variety of green tea in a concentrated form.

The leaves are 4–15 cm (1.6–5.9 in) long and 2–5 cm (0.79–1.97 in) wide. Fresh leaves contain about 4% caffeine, as well as related compounds (including theobromine). Young, light green leaves are preferably harvested for tea production; they have short white hairs on the underside. The older leaves are dark green. Different leaf ages produce different tea qualities because their chemical composition is different. Typically, the top (bud) and the first two to three leaves are harvested for processing. This hand picking is repeated every two to two weeks.

Green tea extract can contain a wide range of anti-inflammatory, anti-oxidant and anti-carcinogenic features. Green tea may be helpful in treating chronic inflammatory conditions. The main antioxidant component in green tea extract is green tea catechins (GTC), which contains four major epicatechin derivatives, that is, epicatechin (epicatechin) , EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG) ), wherein EGCG accounts for more than 40% of the total content. Other components include three types of flavonoids, known as kaempferol, quercetin, and myricetin. One is significantly higher in the amount of myricetin detected in tea and its extracts than in many other plants, and this high concentration of myricetin may have some association with the biological activity of tea and its extracts. It is believed that all components of green tea are combined with Gynostemma to contribute to the synergistic inhibition of a SREBP1c promoter inhibitor activity and/or a combination of Gynostemma and immature apples contribute to IL-1β-stimulated NF-κB. Inhibition of activity.

Gynostemma

Gynostemma is a genus of perennial climbing vines in the cucumber, gourd, and melon families, containing at least 19 species, all native to the East or the Far East. Selected species of Gynostemma include G. aggregatum, G. burmanicum, G. cardiospermum, G. caulopterum, G. compressum, G. guangxiense, G. intermedium, G. laxiflorum, G. laxum, G. longipes, G. microspermum, Gynostemma pentaphyllum (G. pallidinerve), G. papuanum, G. pentagynum, G. pentaphyllum, G. pubescens, G. simplicifolium, Gynostemma pentaphyllum (G) Yixingense) and G. zhejiangense. The Gynostemma extract may be an extract of any of the species of Gynostemma. The term "extract of the genus Gynostemma" means a pure compound, a composition, an extract, a botanical extract, an extract mixture, a botanical extract mixture, in the form of a solid, viscous or liquid substance or preparation, A component of the extract and/or an active agent or component or a combination thereof. The substance or preparation may comprise an active ingredient (a) of a substance of any known variety of Gynostemma in a concentrated form.

It is believed that the combination of all components of Gynostemma with green tea extract contributes to the synergistic inhibition of a SREBP1c promoter inhibitor activity and/or the combination of green tea and immature apples contributes to IL-1β-stimulated NF- Inhibition of κB activity.

Immature apple

Apple and apple products are widely considered to be an important part of the human diet because they contain several nutrient and health-beneficial components (including organic acids, dietary fiber, vitamins and polyphenols) (Schieber et al., 2001). The beneficial effects of these compositions have been attributed to polyphenols and their antioxidant capacity. The main classes of polyphenols in apples are flavan-3-ols (catechins, epicatechins and proanthocyanidin), hydroxycinnamic acids (rancemic acid) Chlorogenic acid) and p-coumaroylquinic acid, dihydrochalcones (phloridzin and phloretin glucoside) and flavonols ( Flavonols) (quercetin and rutin) (Schieber et al., 2001; Alonso-Salces et al., 2005). Interestingly, the levels of these polyphenols are strongly dependent on their variety and maturity (Akiyama et al., 2005; Wu et al., 2007). In particular. Total phenolic content (TPC) (Park et al., 2004; Renard et al., 2007), proanthocyanidins (Akiyama et al., 2005) and flavonoids (Awad et al., 2001) are included in immature apples. 10 times higher than mature.

As noted above, immature apples contain relatively high levels of polyphenols (Adil et al., 2007; Sudha et al., 2007), which have been reported to have a variety of physiological functions, including anti-allergic activity. (Kojima et al., 2000; Akiyama et al., 2005), anti-cancer activity (Yanagida et al., 2000) and anti-atherosclerotic activity (D'Angelo et al., 2007). In order to improve plant polyphenol extraction efficiency, the use of carbohydrate-hydrolyzing enzymes (such as pectinase, cellulase, hemicellulase and polyglucose) has now been introduced to release cell wall complex polyphenols (Meyer et al., 1998; Landbo and Meyer, 2001; Sørensen et al., 2005), and extraction techniques (such as ultrasonic-assisted extraction) (Liyana-Pathirana and Shahidi, 2005; Wang et al., 2008). These enzymes play a role in disintegrating plant cell wall matrices and promoting polyphenol extraction (Renard et al., 2001; Pinelo et al., 2006; Stalikas, 2007; Le B ourvellec et al., 2009). Many processing variables (such as enzymes, matrices, solvents, temperatures, etc.) can affect the efficiency of polyphenol extraction in plants (Meyer et al., 1998). A method for enhancing the extraction efficiency of polyphenols in apple pomace using pectinase has been described (Zheng et al., 2008).

The term "immature apple" means an apple that has not been fully prepared, developed, and matured; an apple that is not easily consumed. Immature apples can come from apple trees of any variety, and in particular from apples of the most widely grown species in the genus Malus. (eg, Malus domestica ). The term "extracted extract of apple" means a pure compound, composition, extract, botanical extract, extract mixture, botanical extract in the form of a solid, a viscous or liquid substance or preparation. a mixture, a component of the extract and/or an active agent or ingredient or a combination thereof. The substance or preparation may comprise an active ingredient of a substance of any known variety of immature apples in a concentrated form.

It is believed that the combination of ingredients of all immature apples with green tea and Gynostemma contributes to the inhibition of IL-1β-stimulated NF-κB activity.

Composition

Some specific examples relate to a composition comprising a green tea extract, an extract of the genus Gynostemma, and optionally an extract of an immature apple, wherein the green tea extract and the Gynostemma pentaphyllum The extract of the genus synergistically inhibits the activity of the SREBP1c promoter, wherein the extract of the green tea, the extract of the genus Gynostemma and the extract of the immature apple inhibit the IL-1β-stimulated NF-κB activity, the composition At least an IC50 is exhibited, wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Some other specific examples relate to a composition comprising a green tea extract, an extract of the genus Gynostemma, and optionally a blend of an immature apple extract, wherein the green tea extract The activity of the SREBP1c promoter is inhibited synergistically with the extract of the genus Gynostemma, wherein the extract of the green tea, the extract of the genus Gynostemma and the extract of the immature apple inhibit the IL-1β-stimulated NF-κB activity, The composition exhibits at least an IC50 wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Some further specific embodiments relate to a composition consisting essentially of a green tea extract, an extract of the genus Gynostemma, and optionally a blend of an immature apple, wherein the green tea The extract and the extract of the genus Gynostemma synergistically inhibit the activity of the SREBP1c promoter, wherein the extract of the green tea, the extract of the genus Gynostemma and the extract of the immature apple inhibit IL-1β-stimulated NF- κB activity, the composition exhibits at least an IC50, wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Some other specific examples relate to a composition comprising an extract of green tea and an extract of the genus Gynostemma, wherein the extract of the green tea and the extract of the genus Gynostemma synergistically inhibit the activity of the SREBP1c promoter, the composition At least an IC50 is exhibited, wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Some other specific examples relate to a composition comprising an extract of green tea and an extract of the genus Gynostemma, wherein the extract of the green tea and the extract of the genus Gynostemma synergistically inhibit the activity of the SREBP1c promoter, The composition exhibits at least an IC50 wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Some other specific examples relate to a composition consisting essentially of an extract of green tea and an extract of the genus Gynostemma, wherein the extract of the green tea and the extract of the genus Gynostemma synergistically inhibit the activity of the SREBP1c promoter The composition exhibits at least an IC50 wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL.

Some further specific examples relate to a composition comprising an extract of green tea, an extract of the genus Gynostemma, and an extract of an immature apple, wherein the extract of the green tea, the extract of the genus Gynostemma, and the The extract of the immature apple inhibits IL-1β-stimulated NF-κB activity, the composition exhibiting at least an IC50, wherein at least 50% inhibition occurs in each extract from about 0.1 μg/mL to about 1000 μg/mL concentration.

Some further specific examples relate to a composition comprising an extract of green tea, an extract of the genus Gynostemma, and an extract of an immature apple, wherein the extract of the green tea, the extract of the genus Gynostemma And the extract of the immature apple inhibits IL-1β-stimulated NF-κB activity, the composition exhibiting at least an IC50, wherein at least 50% inhibition occurs in each from about 0.1 μg/mL to about 1000 μg/mL The concentration of the extract.

Some further specific examples relate to a composition consisting essentially of an extract of green tea, an extract of the genus Gynostemma, and an extract of immature apples, wherein the extract of the green tea, the extract of the genus Gynostemma And the extract of the immature apple inhibits IL-1β-stimulated NF-κB activity, the composition exhibiting at least an IC50, wherein at least 50% inhibition occurs from about 0.1 μg/mL to about 1000 μg/mL The concentration of each extract.

The described compositions may be suitable for administration to a body to support weight management, to prevent, treat or reduce unwanted weight gain, obesity, diabetes, insulin resistance or metabolic syndrome. The individual can be, for example, an obese individual or an individual at risk of obesity.

The compositions may be pharmaceutical (ie, pharmaceutical) compositions, over-the-counter (OTC) compositions, cosmetic compositions, food compositions comprising an effective amount of an extract, at least one component thereof, or a mixture thereof. , food ingredient or dietary supplement composition. In particular, the compositions may be pharmaceutically (i.e., pharmaceutical) compositions comprising a blend of each of an effective amount of green tea and an extract of Gynostemma and optionally immature apples, over-the-counter ( OTC) a composition, a cosmetic composition, a food composition, a food ingredient or a dietary supplement composition.

In such described pharmaceutical compositions for oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, topical or rectal administration, the active extract may be admixed It is administered to animals and humans in a unit dosage form (as a mixture with conventional pharmaceutical carriers). Suitable unit dosage forms include oral-introductory forms (such as lozenges, gel capsules, powders, granules and oral suspensions or solutions), sublingual and buccal administration forms, aerosols, implants, subcutaneous , transdermal, topical, intraperitoneal, intramuscular, intravenous, subepidermal, transdermal, intraspinal and intranasal administration forms and rectal administration forms.

In one example, the described compositions can be provided individually in a solid dosage form (eg, a lozenge or capsule tablet), including, for example, from about 50 mg to about 2 g of individual plant extracts. Any dosage range and dosage within the dosage range provided is suitable, for example, the described compositions may be provided individually in a solid dosage form (eg, a lozenge or capsule lozenge), Approximately 50 mg, about 10 mg, about 150 mg, about 200 mg, about 300 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1 g, and about 2 g. Other dosage ranges between the exemplary ranges and dosages directly mentioned above are also contemplated. The composition can be administered such that the dosage of each plant extract is from about 150 mg per day to about 2 g per day. In some embodiments, the composition can be administered such that a dose of each botanical extract is about 50 mg per day, about 10 mg per day, about 150 mg per day, about 200 mg per day, about 300 mg per day, about every day. 400 mg, about 450 mg per day, about 500 mg per day, about 550 mg per day, about 600 mg per day, about 650 mg per day, about 700 mg per day, about 750 mg per day, about 800 mg per day, about 850 mg per day, about every day. 900 mg, about 950 mg per day, about 1 g per day, and about 2 g per day. The composition can be administered as a single dose or in multiple doses. In one example, the composition can be administered up to three doses per day. For example, the composition can be administered before meals.

The dosage can be selected to provide a level of inhibitory utility in a single unit effective for some individuals, while also allowing for relatively simple dose escalation to provide other levels of effective inhibitory utility for other individuals. In one example, the described compositions can be in a form suitable for oral ingestion. This form can be configured as a single dosage form intended to provide a particular dose of each botanical extract. For example, the single dosage form can be a pill, a lozenge, a capsule or a drink shot. As noted above, the single dosage form can include from about 50 mg to about 2 g of each plant extract in the administered composition.

In an example, the carrier can include saline, buffered saline, dextrose or water. The carrier may include suitable excipients or auxiliaries to facilitate processing of the active compounds into preparations suitable for administration to a subject. The composition can be administered by any suitable route, including oral, intravenous, intramuscular, intraarterial, intraspinal, intraspinal, intraventricular, transdermal, subcutaneous , intraperitoneal, intranasal, parenteral, topical, sublingual or rectal. Oral dosage forms can include lozenges, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like.

In some embodiments, the compositions comprise a pharmaceutically acceptable carrier for a formulation that can be injected. These may in particular be an isotonic, sterile saline solution (sodium dihydrogen phosphate and disodium hydrogen phosphate, sodium chloride, potassium chloride, calcium chloride or magnesium chloride and the like or a mixture of such salts), or dried In particular, the lyophilized composition (which allows for the composition of the injectable solution after the addition of sterile water or physiological saline, as appropriate).

The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions; formulations including sesame oil, arachis oil or aqueous propylene glycol; and sterile powders for immediate preparations of sterile injectable solutions or dispersions. In all cases, the form must be sterile and must be fluid to the extent that easy injectability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi.

An extract comprising green tea, Gynostemma and optionally immature apples can be prepared as a solution of a free base and a pharmaceutically acceptable salt, suitably mixed with a surfactant (such as hydroxypropionate). In the water. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof, as well as in oils. Under normal conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

Inhibitors of SREBP1c promoter activity or performance and IL-1β stimulated NF-κB activity or expression can be formulated into a composition in a neutral or salt form. Pharmaceutically acceptable salts include acid addition salts (formed with free amine groups of the protein) and are either inorganic acids (such as, for example, hydrochloric acid or phosphoric acid) or such organic acids (such as acetic acid, oxalic acid). , tartaric acid, bitter almond acid and the like) are formed. Salts formed with free carboxyl groups may also be derived from inorganic bases such as, for example, sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide or iron hydroxide, and such organic bases such as isopropylamine, Trimethylamine, histidine, procaine and the like). The carrier may also be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycols and the like), suitable mixtures thereof, and vegetable oils. Suitable fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion, and by the use of surfactants. Prevention of the action of microorganisms can be achieved by a variety of different antibacterial and antifungal agents (eg parabens, chlorobutanol, phenol, sorbic acid, sodium thiomersal) ) and similar things are caused. In many instances, it is preferred to include an isotonic agent (e.g., sugar or sodium chloride). Prolonged absorption of such injectable compositions can be caused by the use of agents which delay absorption, such as aluminum monostearate and gelatin, in such compositions.

Sterile injectable solutions are prepared by incorporating such amounts of the required amount of the inhibitor with various other ingredients enumerated above (if required) in a suitable solvent, followed by filtration sterilization. In general, dispersions are prepared by incorporating a variety of different bactericidal active ingredients into a sterile vehicle containing the basic dispersion medium and the required additional ingredients from those enumerated above. In the case of a sterile powder for the preparation of a sterile injectable solution, the preferred method of preparation is vacuum-drying and freeze-drying techniques which produce from the prior-sterilized filtered solution with the active ingredient plus any additional A powder of the desired ingredients.

After formulation, the solution can be administered in a manner compatible with the dosage formulation and in such amounts that are therapeutically effective. Such formulations are readily administered in a variety of different dosage forms, such as the types of injectable solutions described above, but drug release capsules and the like may also be employed.

For parenteral administration to an aqueous solution, for example, the solution should be suitably buffered if desired, and the liquid diluent first rendered isotonic with sufficient saline or glucose. These particular aqueous solutions are particularly suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. In view of the present invention, sterile aqueous media that can be employed will be known to those skilled in the art. For example, a dose can be dissolved in 1 ml of isotonic NaCl solution and added to 1000 ml of hypodermoclysis fluid or injected at the recommended site of injection. Some changes in dosage will necessarily occur, depending on the condition of the individual to be treated. In any event, the person responsible for the administration will determine the appropriate dosage for the individual individual. Inhibitors of SREBP1c promoter activity or performance and IL-1β stimulated NF-κB activity or expression can be formulated in a therapeutic mixture to contain from about 50 mg to about 2 g of each plant extract or component. Multiple doses can also be administered.

In addition to such extracts that are formulated for parenteral administration, such as intravenous or intramuscular injection, other pharmaceutically acceptable forms include, for example, lozenges or other solids for oral administration. Administration; liposome formulation; timed release capsules; and any other form used today.

In certain embodiments, the described compositions will exhibit at least an IC50 wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL. Alternatively, the described compositions will exhibit at least an IC50 wherein at least 50% inhibition occurs at a concentration of each extract of less than about 50 μg/mL. Alternatively, the described compositions will exhibit at least an IC50 wherein at least 50% inhibition occurs at less than about 40 μg/mL, less than about 30 μg/mL, less than about 20 μg/mL, less than about 10 μg/ The concentration of each extract in mL, less than about 5 μg/mL or less than about 2 μg/mL.

In certain embodiments, the composition comprising a blend of green tea and Gynostemma extract inhibits SREBP1c promoter activity by at least about 10% relative to the absence of the extract, alternatively, at least about 50%, alternatively, at least about 75%, alternatively, at least about 90%, or at least about 100%. This inhibition is synergistic. Surprisingly, it has been demonstrated that percentage inhibition is a significantly higher and synergistic blend of green tea and Gynostemma (at 10 μg compared to the individual extracts and a predicted utility). Test concentrations of each extract of /mL, 20 μg/mL, 40 μg/mL, and 60 μg/mL). See Figures 1A-D .

In certain embodiments, the composition of the blend comprising the extracts of green tea, Gynostemma, and immature apples inhibits IL-1β-stimulated NF-κB activity relative to the lack of such extracts. At least about 10%, alternatively, at least about 50%, alternatively, at least about 75%, alternatively, at least about 90%, or at least about 100%. Surprisingly, it has been demonstrated that a blend of immature apple, green tea and Gynostemma extract dose-dependently inhibits IL, as compared to the pure compound Bay 11-7085 used as a positive control. -1β-stimulated NF-κB activity (test concentration of each extract at 100 pg/ml). See Figure 3 .

The following exemplary compositions (having an amount of each active ingredient within the indicated ranges) will provide one of several compositions that can be used to treat or prevent obesity or the like in one body:

method

The composition can be adapted for administration to a body to support weight management. In one example, the composition can be administered to a subject to treat or prevent obesity. Accordingly, certain embodiments are directed to a method for treating or preventing obesity in a subject comprising administering to the individual a sufficient amount of an extract comprising green tea, an extract of Gynostemma, and an alternative a composition of a blend of an immature apple extract exhibiting at least an IC50 wherein at least 50% inhibition occurs from about 0.1 μg/mL to about 1000 μg/mL of each extract Concentration, and wherein the composition reduces the weight of the individual by at least 5%. The green tea extract and the Gynostemma extract synergistically inhibit the activity of the sterol regulatory element binding protein 1c (SREBP1c) promoter. The green tea extract, the Gynostemma extract and the extract of the immature apple inhibit IL-1β-stimulated NF-κB activity.

Some further specific embodiments relate to a method for inhibiting the activity of a sterol regulatory element binding protein 1c (SREBP1c) promoter in a body comprising administering to the individual a sufficient amount of an extract comprising a green tea And a composition of an extract of the genus Gynostemma, wherein the extract of the green tea and the extract of the genus Gynostemma synergistically inhibit the activity of the SREBP1c promoter, and wherein the composition exhibits at least an IC50, wherein at least 50% inhibition occurs at A concentration from about 0.1 μg/mL to about 1000 μg/mL.

Still further specific embodiments relate to a method for inhibiting IL-1β-stimulated NF-κB activity in a body comprising administering to the individual a sufficient amount of an extract comprising green tea, An extract of Gynostemma and an extract of an immature apple, wherein the extract of green tea, the extract of Gynostemma and the extract of the immature apple inhibit IL-1β-stimulated NF- κB activity, the composition exhibits at least an IC50, wherein at least 50% inhibition occurs at a concentration of from about 0.1 μg/mL to about 1000 μg/mL.

In the methods described, the administration is accomplished to treat or prevent at least one of sugar addiction, unwanted weight gain, obesity, or metabolic syndrome. The individual is at risk of being obese or likely to have obesity. The administered composition may be in a form suitable for oral ingestion, such as a pill, a lozenge, a capsule, a capsule tablet, a sugar lozenge, a powder, a liquid, a gel, a syrup , a slurry, a suspension, a supplement. The administered composition can be a pharmaceutically acceptable drug. The administered composition can be an over-the-counter drug. The administered composition can be in a food product. Example

Example 1: Effect of various doses of green tea and Gynostemma and a blend of green tea and Gynostemma on SREBP1c activity

The purpose of this study was to determine the utility (i.e., percent inhibition) of the extract of green tea and Gynostemma or a combination of such extracts on SREBP1c activity. The concentrations of the extracts at 10 μg/mL ( Fig. 1A ), 20 μg/mL ( Fig. 1B ), 40 μg/mL ( Fig. 1C ), and 60 μg/mL ( Fig. 1D ) were used.

The SREBP1c promoter activity study was carried out as follows.

The HEPG2 cell line was stably transfected with a Lucifer 6 transfection reagent (Roche, Indianapolis, IN) under the control of the full-length human SREBP1c promoter with a luciferase reporter vector (pGL 4.27). The stabilized cells were grown in a 96 well plate in 25 mM glucose DMEM medium and treated with extract for 18 hr to maximally stimulate SREBP1c promoter activity. After 18 hr of incubation, the medium was removed from the cells and the cells were washed once with 200 ul of phosphate buffered saline (PBS). 25 μl of passive lysis buffer (Biotium, Hayward, CA) was then added to each well and incubated for 10 min at room temperature to dissolve the cells. After this, 100 μl of luciferin (Biotium, Hayward, CA) was added and the light was read in a disc reader. Data are expressed as a percentage inhibition relative to untreated cells (set to 0%).

Surprisingly, it has been demonstrated that this percentage inhibition is a significantly higher and synergistic blend of green tea and Gynostemma compared to the individual extracts and a predicted utility (at 10 Μg/mL ( Figure 1A ), 20 μg/mL ( Figure 1B ), 40 μg/mL ( Figure 1C ), and 60 μg/mL ( Figure 1D ) for each extract). See Figures 1A-D .

Example 2: Mathematical calculation of synergy between green tea and Gynostemma extract on SREBP1c promoter activity

Figure 2 shows an equivalent plot of data generated by using the Loewe additive model with synergy <1; addition = 1; antagonism > 1 (see equation below). Combination index = Ca, r + Cb, r Icx, a Icx, b Ca, r = concentration of green tea extract in synergistic experiments ICx, a = concentration equal to synergistic green tea extract Cb, r = in synergistic experiments The concentration of the extract of the genus Gynostemma, ICx, b = the concentration of the synergistic effect of Gynostemma extract

All doses of the blend tested were calculated to be highly synergistic, which is a CI <1.

Example 3: Effect of blend of immature apple, green tea and Gynostemma extract on IL-1β-stimulated NF-κB activity

The study was carried out as follows.

Human A549 cells were stably transfected with a pNFκB-Luc plastid (Clontech, Mounta in View, CA) using Fugene 6 transfection reagent (Roche, Indianapolis, IN). To assess the anti-inflammatory activity of the samples, the cells were seeded at 5 X 104/well in a white, 96 well, clear bottom microtiter plate and incubated overnight in OptiPro serum-free medium. The next day, the cells were exposed to a blend of immature apple, green tea and Gynostemma extract and IL-1β (100 pg/ml). Six hours after the addition of IL-1β, the cells were lysed and the relative amount of luciferase was assessed using a luciferin reagent from Biotium (Hayward, CA). The pure compound Bay 11-7085 was used as a positive control. Data are expressed as a percentage control in which the relative luminescence unit caused by control cells exposed only to IL-1β is set at 100%.

It was demonstrated that a blend of immature apple, green tea and Gynostemma extract dose-dependently inhibited IL-1β-stimulated NF-κB activity. See Figure 3 .

Although the present invention has been described with reference to the specific exemplary embodiments, it is apparent that various modifications and changes may be made to the specific embodiments without departing from the spirit and scope of the invention. The following claims (including all equivalents) are intended to define the spirit and scope of the invention.

Figure 1A depicts a bar graph showing the utility of green tea (10 μg/mL) and Gynostemma (10 μg/mL) on the SREBP1c promoter activity;

Figure 1B depicts a bar graph showing the utility of green tea (20 μg/mL) and Gynostemma (20 μg/mL) on the SREBP1c promoter activity;

Figure 1C depicts a bar graph showing the utility of green tea (40 μg/mL) and Gynostemma (40 μg/mL) on the SREBP1c promoter activity;

Figure 1D depicts a bar graph showing the utility of green tea (60 μg/mL) and Gynostemma (60 μg/mL) on the SREBP1c promoter activity;

Figure 2 depicts an equivalent diagram of data generated using the Loewe addition model;

Figure 3 depicts a graph showing the utility of a blend of immature apple, green tea and Gynostemma extracts on IL-1β stimulated NF-κB activity.

(no)

Claims (22)

A composition comprising: an extract of green tea; an extract of Gynostemma ; and, optionally, an extract of an immature apple, wherein the extract of the green tea and the extract of the genus Gynostemma Synergistically inhibiting the activity of a sterol regulatory element binding protein 1c (SREBP1c) promoter; wherein the green tea extract, the Gynostemma extract and the immature apple extract inhibit IL-1β-stimulated nuclear factor Activated B cell kappa light chain enhancer (NF-κB) activity; the composition exhibits at least an IC50, wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL. A composition comprising: an extract of green tea; and an extract of Gynostemma, wherein the extract of green tea and the extract of Gynostemma synergistically inhibit a sterol regulatory element binding protein 1c (SREBP1c) promoter Activity; the composition exhibits at least an IC50 wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL. A composition comprising: an extract of green tea; an extract of the genus Gynostemma; and an extract of an immature apple, wherein the extract of the green tea, the extract of the genus Gynostemma, and the immature apple Extract inhibits IL-1β-stimulated nuclear factor-activated B cell kappa light chain enhancer (NF-κB) activity; the composition exhibits at least an IC50, wherein at least 50% inhibition occurs from about 0.1 μg/mL to about The concentration of each extract at 1000 μg/mL. The composition of any one of claims 1 to 3, wherein the total amount of the extracts in the composition is between about 0.005 weight percent and about 50 weight percent or between about 0.0033 weight percent and about 33.3 weight percent between. The composition of any one of claims 1 to 4, wherein the composition is in a form suitable for oral ingestion. The composition of claim 5, wherein the form is selected from the group consisting of: a pill, a lozenge, a capsule, a capsule, a sugar-coated tablet, a powder, a liquid , a gel, a syrup, a slurry, a suspension, a supplement. The composition of any one of claims 1 to 6, wherein the composition is a pharmaceutically acceptable drug. The composition of any one of claims 1 to 6, wherein the composition is an over-the-counter drug. The composition of any of claims 1-6, wherein the composition is in a food product. The composition of any one of claims 1-9, wherein the composition is for treating or preventing obesity. The composition of claim 10, wherein the composition reduces the weight of an obese individual by at least 5%. The composition of any of claims 1-11, further comprising at least one of a pharmaceutically or nutraceutically acceptable carrier, adjuvant or excipient. A method for treating or preventing obesity in a body, comprising: administering to the individual a sufficient amount of a composition comprising: an extract of green tea; an extract of Gynostemma; and optionally An extract of an immature apple exhibiting at least an IC50 wherein at least 50% inhibition occurs at a concentration of each extract from about 0.1 μg/mL to about 1000 μg/mL; and wherein the composition is reduced The individual has a weight of at least 10%. The method of claim 13, wherein the extract of the green tea and the extract of the genus Gynostemma synergistically inhibit the activity of the sterol regulatory element binding protein 1c (SREBP1c) promoter. The method of claim 13, wherein the green tea extract, the Gynostemma extract, and the extract of the immature apple inhibit IL-1β-stimulated NF-κB activity. A method for inhibiting the activity of a sterol regulatory element binding protein 1c (SREBP1c) promoter in a body, comprising: administering to the individual a sufficient amount of an extract comprising the following composition, green tea; An extract of the genus Gynostemma, wherein the extract of the green tea and the extract of the genus Gynostemma synergistically inhibit the activity of the SREBP1c promoter; and wherein the composition exhibits at least an IC50, wherein at least 50% inhibition occurs at about 0.1 μg from about 0.1 μg /mL to a concentration of about 1000 μg / mL. A method for inhibiting the activity of IL-1β-stimulated NF-κB in a body, comprising: administering to the individual a sufficient amount of an extract comprising the following composition, green tea; An extract of an immature apple, wherein the extract of the green tea, the extract of the genus Gynostemma, and the extract of the immature apple inhibit IL-1β-stimulated NF-κB activity; the composition At least an IC50 is exhibited, wherein at least 50% inhibition occurs at a concentration from about 0.1 μg/mL to about 1000 μg/mL. The method of any one of claims 16-17, wherein the administering is completed to treat or prevent at least one of a sugar addiction, unwanted weight gain, obesity, or metabolic syndrome. The method of any one of claims 16-17, wherein the individual is obese. The method of any one of claims 16-17, wherein the individual is at risk of obesity. The method of any one of claims 16 to 20, wherein the composition is in a form suitable for oral ingestion. The method of claim 21, wherein the form is selected from the group consisting of: a pill, a lozenge, a capsule, a capsule tablet, a sugar-coated tablet, a powder, a liquid, a gel , a syrup, a slurry, a suspension, a supplement.