Composition for preventing or treating lipid metabolism-related diseases comprising ginger juice and lemon juice as active ingredients

Abstract

The present invention relates to a composition for preventing or treating lipid metabolism-related diseases comprising ginger juice and lemon juice as active ingredients. The activities of a mixed solution of ginger juice and lemon juice in improving the lipid levels in plasma, the lipid levels in the liver, and the lipid levels in feces, and in inhibiting lipid deposition in the aorta were analyzed, and the activity of the active ingredients in ginger juice and lemon juice as inhibitors against target receptors, and the physicochemical and pharmacokinetic properties thereof were analyzed, whereby it was confirmed that ginger juice and lemon juice can be used for preventing, alleviating, or treating lipid metabolism-related diseases.

Description

A composition for the prevention or treatment of lipid metabolism-related diseases comprising ginger juice and lemon juice as active ingredients

[0001] The present invention relates to a composition for the prevention or treatment of lipid metabolism-related diseases comprising ginger juice and lemon juice as active ingredients.

[0002] Lemons are native to the Himalayas and thrive in relatively cool climates with little variation. They are widely cultivated in Italy, Spain, California in the United States, and Australia, but those grown along the Mediterranean coast are of the highest quality.

[0003] It has a strong sour taste due to its high content of vitamin C and citric acid. Lemon oil is extracted from the peel and used as an ingredient in beverages, perfumes, and lemonade, while the juice is used as an ingredient in beverages, vinegar, and cosmetics, and is also used as a flavoring when making confectionery.

[0004] Ginger is also known as Saeang or Saeyang. It is native to Southeast Asia and is cultivated as a vegetable. The rhizome grows horizontally, is fleshy, lumpy, and yellow, with a spicy taste and fragrant smell. At each node of the rhizome, false stems formed from leaf sheaths stand upright, reaching a height of 30 to 50 cm, with leaves arranged in two rows at the top. The leaves are alternate and linear-lanceolate, tapering at both ends and forming long leaf sheaths at the base.

[0005] In traditional Korean medicine, the dried rhizome of ginger is used as a medicinal herb. Ginger is used to treat chills, fever, headache, vomiting, cough, and phlegm caused by the common cold, and is also effective for abdominal pain, diarrhea, and bloating caused by food poisoning, so it is often brewed in boiling water and consumed as tea.

[0006] Pharmacological effects such as promoting gastric juice secretion, enhancing digestive power, cardiac stimulant action, promoting blood circulation, and antibacterial action have been reported. In Chinese, it is also called Jiang Gen (Ginger Root), Mu Jiang (Mother Ginger), Bai La Yun (Hundred Spicy Yun), Yan Liang Xiao Zi (Cool and Spicy Kid), Yin Di Cao (Ground Herb), Zi Jiang (Son Ginger), Zi Jiang (Purple Ginger), Gan Jiang (Dried Ginger). In addition, the root stalks are dried, ground, and used as spices in bread, snacks, curry, sauce, pickles, etc. The skin is peeled off, boiled, and then put into syrup to make preserves, and also used to make fresh ginger tea and fresh ginger wine.

[0007] On the other hand, with the increasing mortality rate due to adult diseases in recent years, attention has been focused on obesity. Accordingly, various health supplements with anti-obesity efficacy have been successively launched in the domestic and global pharmaceutical industries. Moreover, due to economic growth, the intake status has improved, but compared with this, the lack of exercise has become more serious, resulting in a rapid increase in the number of obese people, and the increase in adult diseases caused by this has become a social problem. In addition, as the eating habits of the Korean people become Westernized, chronic lifestyle diseases such as adult lifestyle diseases are expected to increase in the future, and as the aging society progresses, the demand for silver foods targeting the elderly population is also expected to increase.

[0008] Obesity is a state in which fat accumulates excessively in the body due to metabolic disorders, which is caused by a calorie imbalance phenomenon where calorie intake exceeds the energy required for growth and physical activities. Generally, it refers to the case where the fat in the body is more than 25% of the body weight in men and 30% or more in women. In particular, obesity is not only the cause of various metabolic diseases such as diabetes, hyperlipidemia, cardiovascular diseases, and arteriosclerosis, but the increase in the mortality rate due to obesity is clearly shown in metabolic diseases, gallbladder diseases, hormone-sensitive cancers, and gastrointestinal cancers. Obesity also increases the risk of physical diseases such as non-fatal pain, arthritis, infertility, and mental diseases such as the decline of mental and social functions.

[0009] Strategies for treating obesity and related disorders include dietary restriction, increased physical activity, pharmacological approaches, and even surgery, which are selected based at least in part on the severity of obesity exhibited by the subject as well as the degree of weight loss the individual attempts to achieve. For example, for individuals who are only mildly overweight, treatments such as low-calorie, low-fat diets and / or regular exercise are often appropriate. However, due to the difficulty of maintaining long-term weight loss through dietary and behavioral modifications, interest in other treatment methods, particularly pharmacotherapy, has increased.

[0010] Although various therapeutic agents or appetite suppressants have been released to treat the aforementioned obesity and related diseases, there is a problem in that side effects such as paresthesia, alopecia, parosmia, amenorrhea, and aphasia may occur.

[0011]

[0012] Accordingly, the inventors confirmed the activity of a mixture of ginger juice and lemon juice in improving lipid levels in plasma, lipid levels in the liver, and lipid levels in feces, and the activity of inhibiting lipid depletion in the aorta, and confirmed the activity of the active ingredients in ginger juice and lemon juice as inhibitors of target receptors, as well as physicochemical and pharmacokinetic characteristics, thereby completing the present invention.

[0013] The objective of the present invention is to provide a food composition for the prevention or improvement of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0014] Another objective of the present invention is to provide a health functional food composition for the prevention or improvement of lipid-related metabolic diseases, comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0015] Another objective of the present invention is to provide a pharmaceutical composition for the prevention or treatment of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0016] Another objective of the present invention is to provide a method for preventing or treating lipid-related metabolic diseases, comprising the step of administering the pharmaceutical composition to an individual.

[0017] To achieve the above objective, the present invention provides a food composition for the prevention or improvement of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0018] In addition, the present invention provides a health functional food composition for the prevention or improvement of lipid-related metabolic diseases, comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0019] In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0020] In addition, the present invention provides a method for preventing or treating lipid-related metabolic diseases, comprising the step of administering the above pharmaceutical composition to an individual.

[0021] The present invention relates to a composition for the prevention or treatment of lipid metabolism-related diseases comprising ginger juice and lemon juice as active ingredients. It has been confirmed that a mixture of ginger juice and lemon juice has activity in improving lipid levels in plasma, lipid levels in the liver, and lipid levels in feces, and activity in inhibiting lipid accumulation in the aorta. Additionally, the activity of the active ingredients in ginger juice and lemon juice as inhibitors of target receptors, as well as physicochemical and pharmacokinetic properties, have been confirmed, which can be usefully utilized in related industries.

[0022] Figure 1 shows the effects of ginger juice and lemon juice on total cholesterol and triglycerides in the plasma.

[0023] Figure 2 shows the effects of ginger juice and lemon juice on HDL-C, LDL-C, and atheroma formation index (AIP) in hyperlipidemia mice.

[0024] Figure 3 shows the effects of ginger juice and lemon juice on total cholesterol and triglycerides in the liver.

[0025] Figure 4 shows the effects of ginger juice and lemon juice on total cholesterol and triglycerides in cholesterol feces.

[0026] Figure 5 shows microanatomical images of histological sections of the aorta of mice treated with ginger juice and lemon juice.

[0027] Figure 6 shows the binding energy of molecules interacting with the target receptor 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) in ginger juice and lemon juice.

[0028] Figure 7 shows the results of molecular radar plot analysis of ginger juice and lemon juice.

[0029] Figure 8 is a figure regarding the pharmacokinetic potential of various molecules, visually expressing and predicting their gastrointestinal absorption and brain penetration capabilities using the Boiled Egg Test.

[0030] The terminology used in this specification is used to appropriately describe preferred embodiments of the present invention, and may vary depending on the intent of the user or operator, or the conventions of the field to which the present invention belongs. Therefore, the definitions of these terms should be based on the content throughout this specification. Throughout the specification, when a part is described as "comprising" a certain component, unless specifically stated otherwise, this means that it does not exclude other components but may include additional components.

[0031] Throughout this specification, '%' used to indicate the concentration of a particular substance is (w / w) % for solid / solid, (w / v) % for solid / liquid, and (v / v) % for liquid / liquid, unless otherwise noted.

[0032]

[0033] The present invention provides a food composition for the prevention or improvement of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0034] In addition to containing the active ingredient of the present invention, the food composition of the present invention may contain various flavoring agents or natural carbohydrates, etc., as additional ingredients, as in conventional food compositions.

[0035] Examples of the natural carbohydrates described above include monosaccharides, e.g., glucose, fructose, etc.; disaccharides, e.g., maltose, sucrose, etc.; polysaccharides, e.g., dextrin, cyclodextrin, etc., and conventional sugars, and sugar alcohols such as xylitol, sorbitol, erythritol, etc. The flavoring agents described above may advantageously use natural flavoring agents (taumatin), stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.), and synthetic flavoring agents (saccharin, aspartame, etc.). The food composition of the present invention may be formulated in the same manner as the pharmaceutical composition described above and used as a functional food or added to various foods. Foods to which the composition of the present invention may be added include, for example, beverages, meat, chocolate, food products, confectionery, pizza, ramen, other noodles, chewing gum, candy, ice cream, alcoholic beverages, vitamin complexes, and health supplements.

[0036] In addition, the above food composition may contain, in addition to the active ingredient, various nutritional supplements, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. Furthermore, the food composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice beverages, and vegetable beverages.

[0037] The functional food composition of the present invention may be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. In the present invention, the term "health functional food composition" refers to a food manufactured and processed using raw materials or ingredients having functional properties useful to the human body pursuant to Article 6727 of the Act on Health Functional Foods, and means consuming it for the purpose of obtaining effects useful for health uses, such as regulating nutrients or physiological actions regarding the structure and function of the human body. The health functional food of the present invention may include conventional food additives, and unless otherwise stipulated, suitability as a food additive is determined according to the specifications and standards for the relevant item in accordance with the general provisions and general test methods of the Food Additives Codex approved by the Ministry of Food and Drug Safety. Items listed in the aforementioned "Food Additives Codex" include, for example, chemically synthesized compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamon acid; and natural additives such as persimmon dye, licorice extract, crystalline cellulose, sorghum dye, and guar gum. Examples include mixed preparations such as L-sodium glutamate preparations, alkaline additives for noodles, preservative preparations, and tar dye preparations. For instance, a health functional food in tablet form may be produced by granulating a mixture of the active ingredient of the present invention with excipients, binders, disintegrants, and other additives using a conventional method, and then compression molding by adding a lubricant, etc., or by directly compression molding the mixture. Additionally, the health functional food in tablet form may contain a binder, etc., as necessary. Among health functional foods in capsule form, hard capsules may be manufactured by filling a conventional hard capsule with a mixture of the active ingredient of the present invention mixed with additives such as excipients, and soft capsules may be manufactured by filling a capsule base such as gelatin with a mixture of the active ingredient of the present invention mixed with additives such as excipients. The soft capsules may contain plasticizers such as glycerin or sorbitol, coloring agents, preservatives, etc., as necessary.A health functional food in the form of a pill can be prepared by molding a mixture of the active ingredient of the present invention, excipients, binders, disintegrants, etc., using a previously known method, and if necessary, it can be coated with sucrose or other coating agents, or the surface can be coated with a substance such as starch or talc. A health functional food in the form of a granule can be prepared by making a mixture of the active ingredient of the present invention, excipients, binders, disintegrants, etc., into a granular form using a previously known method, and may contain flavoring agents, stimulating agents, etc., if necessary.

[0038] In one embodiment of the present invention, the mixture may be obtained by mixing ginger juice and lemon juice in a weight ratio of 1:1, but is not limited thereto.

[0039] In one embodiment of the present invention, the ginger juice may contain 4-gingerol, 6-gingerol, or 6-gingediol as a component, but is not limited thereto.

[0040] In one embodiment of the present invention, the lemon juice may contain eriodictyol, hesperidin, isorhamnetin, or rutin as a component, but is not limited thereto.

[0041] In one embodiment of the present invention, the mixture may reduce the total cholesterol or triglyceride content in the plasma, but is not limited thereto.

[0042] In one embodiment of the present invention, the mixture may increase the total cholesterol or triglyceride content in the feces, but is not limited thereto.

[0043] In one embodiment of the present invention, the mixture may reduce lipid deposition in the aorta, but is not limited thereto.

[0044]

[0045] In one embodiment of the present invention, the mixture may reduce the thickness of the aortic intima, but is not limited thereto.

[0046] In one embodiment of the present invention, the 4-gingerol may have a binding energy of -5.1 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), but is not limited thereto.

[0047] In one embodiment of the present invention, the 6-gingerol may have a binding energy of -5.5 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), but is not limited thereto.

[0048] In one embodiment of the present invention, the 6-gingediol may have a binding energy of -5.6 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), but is not limited thereto.

[0049] In one embodiment of the present invention, the eriodictyol may have a binding energy of -7.5 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), but is not limited thereto.

[0050] In one embodiment of the present invention, the hesperidin may have a binding energy of -9.4 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), but is not limited thereto.

[0051] In one embodiment of the present invention, the isorhamnetin may have a binding energy of -7.2 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), but is not limited thereto.

[0052] In one embodiment of the present invention, the rutin may have a binding energy of -7.9 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), but is not limited thereto.

[0053] In one embodiment of the present invention, the lipid-related metabolic disease may be one or more selected from the group consisting of diabetes, hyperlipidemia, fatty liver, hepatitis, cirrhosis, arteriosclerosis, hypertension, cardiovascular disease, and metabolic syndrome in which the above diseases occur simultaneously, and preferably may be hyperlipidemia, but is not limited thereto.

[0054]

[0055] In addition, the present invention provides a health functional food composition for the prevention or improvement of lipid-related metabolic diseases, comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0056]

[0057] In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

[0058] The pharmaceutical composition of the present invention may additionally include an adjuvant in addition to the active ingredient. Any adjuvant known in the art may be used without limitation, but, for example, Freund's complete or incomplete adjuvant may be further included to increase the immunity.

[0059] The pharmaceutical composition according to the present invention may be prepared in a form in which an active ingredient is incorporated into a pharmaceutically acceptable carrier. Here, the pharmaceutically acceptable carrier includes carriers, excipients, and diluents commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers that can be used in the pharmaceutical composition of the present invention are not limited to these, but may include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0060] The pharmaceutical composition of the present invention may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external formulations, suppositories, or sterile injectable solutions, each according to conventional methods.

[0061] When formulating, the product may be prepared using diluents or excipients such as commonly used fillers, volume expanders, binders, wetting agents, disintegrants, and surfactants. Solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules, and such solid dosage forms may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc., with the active ingredient. In addition, lubricants such as magnesium stearate and talc may also be used in addition to simple excipients. Liquid dosage forms for oral administration include suspensions, liquid formulations, emulsions, and syrups, and may contain various excipients, such as wetting agents, sweeteners, flavoring agents, and preservatives, in addition to commonly used diluents such as water and liquid paraffin. Preparations for parenteral administration include sterile aqueous solutions, water-insoluble solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Water-insoluble solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Bases for suppositories may include Witepsol, Tween 61, cocoa paste, laurin paste, glycerogelatin, etc.

[0062] The pharmaceutical composition according to the present invention may be administered to an individual by various routes. Any mode of administration may be anticipated, for example, by oral, intravenous, intramuscular, subcutaneous, or intraperitoneal injection.

[0063] The dosage of the pharmaceutical composition according to the present invention is selected by taking into consideration the individual's age, weight, gender, physical condition, etc. It is obvious that the concentration of the active ingredient included in the pharmaceutical composition can be selected in various ways depending on the subject.

[0064] The above pharmaceutical composition can be formulated into various oral or parenteral administration forms.

[0065] Oral dosage forms include, for example, tablets, pills, hard and soft capsules, liquids, suspensions, emulsifiers, syrups, granules, etc., and these dosage forms may additionally contain diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine) and lubricants (e.g., silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycol) in addition to the active ingredient. Furthermore, the tablet may contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, and in some cases may contain disintegrants or boiling mixtures such as starch, agar, alginic acid or its sodium salt and / or absorbents, coloring agents, flavoring agents and sweeteners. The above formulation can be prepared by conventional mixing, granulation, or coating methods.

[0066] In addition, representative formulations for parenteral administration are injectable preparations, and solvents for injectable preparations include water, Ringer's solution, isotonic saline, or suspensions. The sterile fixation oil of the above injectable preparation can be used as a solvent or suspension medium, and any non-irritating fixation oil, including mono- and di-glycerides, can be used for this purpose.

[0067] In addition, the above-mentioned injectable formulation may use fatty acids such as oleic acid.

[0068] The term "prevention" above refers to any act that reduces the frequency or severity of pathological phenomena. Prevention may be complete or partial. In this case, it may refer to a phenomenon in which lipid metabolism-related diseases within an individual are reduced compared to the case where the composition is not used.

[0069] The above "treatment" refers to any act of clinical intervention intended to alter the natural processes of the target or cell to be treated, and may be performed during the progression of a clinical pathological condition or to prevent it. The intended therapeutic effects may include preventing the onset or recurrence of the disease, alleviating symptoms, reducing all direct or indirect pathological consequences associated with the disease, preventing metastasis, slowing the rate of disease progression, alleviating or temporarily resolving the disease state, or improving the prognosis.

[0070]

[0071] In addition, the present invention provides a method for preventing or treating lipid-related metabolic diseases, comprising the step of administering the above pharmaceutical composition to an individual.

[0072] The term "individual" as used in this invention refers to a subject requiring a method for the prevention, control, or treatment of a disease, and may be used without limitation and includes humans, dogs, monkeys, cats, rodents, e.g., mice, genetically modified mice, etc. More specifically, it refers to mammals such as humans or non-human primates, mice, rats, dogs, cats, horses, and cattle.

[0073] The present invention will be explained in more detail through the following examples. However, the following examples are intended only to illustrate the content of the present invention and do not limit the present invention.

[0074]

[0075] <Preparation Example> Preparation of ginger juice and lemon juice

[0076] The ginger rhizomes and lemon fruits were purchased from a herbalist in Oujda. The plant identification was evaluated by Professor Fennane Mohammed, a botanist at the scientific research institute in Rabat.

[0077] To obtain the ginger juice of the present invention, ginger (Zingiber officinale Roscoe) was ground in a blender at room temperature until juice was produced, and the ground material was filtered to obtain ginger juice. The obtained ginger juice was placed in a drying oven and dried to obtain dried ginger juice (GJ). In addition, lemon (Citrus limon L.) juice (LJ) was obtained in the same manner as above. To obtain the ginger juice and lemon juice, the obtained ginger juice and lemon juice were mixed in equal weights to prepare a formulation.

[0078]

[0079] <Example 1> Analysis Method

[0080] 1-1. Analysis of Polyphenol Content

[0081] The polyphenol content in ginger juice and lemon juice was measured using the Folin Ciocalteu colorimetric method. 1 mL of Folin Ciocalteu reagent (0.2 mN) was added to 0.2 mL of ginger juice and 0.2 mL of lemon juice, respectively, and incubated at room temperature for 5 minutes, after which 0.8 mL of 7.5% sodium carbonate was added. Subsequently, the mixture was incubated for 1 hour, and the optical density (OD) was calculated using a mixture of 0.2 mL of methanol, 1 mL of Folin Ciocalteu reagent, and 0.8 mL of 7.5% sodium carbonate as a blank. 760 ) was measured.

[0082] To quantify polyphenols in ginger juice and lemon juice, a calibration curve was constructed using gallic acid as a standard, and all measurements were repeated three times to ensure precision.

[0083]

[0084] 1-2. Analysis of Flavonoid Content

[0085] The flavonoid content in ginger juice and lemon juice was evaluated by measuring the light absorbance of the complex at 430 nm after forming a complex with aluminum. This measurement method was based on the method of Chen et al. (2015) and used a partially modified procedure.

[0086] Ginger juice and lemon juice were each diluted to 0.5 mg / mL, and then ionized water and sodium nitrate solution were added and mixed. After 6 minutes, aluminum chloride solution was added, and after 5 minutes, sodium hydroxide solution was added. Water, sodium nitrate, and aluminum chloride were used as blank solutions, and absorbance was measured at 430 nm. Flavonoid content was quantified based on a calibration curve prepared using quercetin as a standard. Through this process, the quercetin equivalent (mg QE / g) per 1 g of ginger juice and lemon juice, respectively, was calculated. Antioxidant activity was measured using a spectrophotometer at 470 nm after adding ginger juice and lemon juice to the emulsion, with BHA (butylhydroxyanisole) used as the standard antioxidant compound. All measurements were repeated three times to ensure the reliability of the experimental data.

[0087]

[0088] 1-3. Qualitative Analysis of Phenol Compounds

[0089] Qualitative analysis of phenolic compounds in ginger juice and lemon juice (GJ and LJ) was performed using a system combining high-performance liquid chromatography (HPLC) and mass spectrometry (Waters Alliance 2695 system, Milford, MA, USA). Chromatographic separation was carried out on a reversed-phase C18 column with a pore size of 5 μm and a 250 Y 4.6 mm diameter. The mobile phase consisted of two solvents. Solvent A was a mixture of water and formic acid in a 90:10 (v / v) ratio, and Solvent B was a mixture of water, methanol, and acetonitrile in a 40:50:10 (v / v / v) ratio.

[0090] The elution of phenolic compounds was performed using the following gradation conditions: initially, 88% A and 12% B were used for 20 minutes, followed by the application of 100% B for 10 minutes, and then the solution was returned to 88% A and 12% B and maintained for 15 minutes. The eluent flow rate was maintained constant at 1 mL / min, and the injection volume for each sample was set to 20 μL. All analyses were performed at room temperature. For sample preparation, standard solutions, ginger, and lemon juice were dissolved in pure methanol and filtered through a membrane filter (Millipore) with a pore size of 0.45 μm.

[0091]

[0092] 1-4. Analysis of the Effects of Ginger and Lemon Juice on Chronic Hyperlipidemia

[0093] The high-fat diet consisted of 2% cholesterol, 16% fat, and 0.2% deoxycholic acid, and was prepared based on 81.8% of the standard diet. The standard diet used Sonabetail Sausité (Morocco Ouzda) products.

[0094] In addition, the hyperlipidemia-improving effects of ginger juice and lemon juice were analyzed. Ninety adult male white rats (body weight 20–25 g) were used as the experimental group; they were divided into nine groups of ten rats each and provided with a high-fat diet for 12 weeks. Additionally, ten rats were fed a standard diet and used as a normal control group. Ginger juice and lemon juice were administered at doses of 250 mg / kg and 500 mg / kg, respectively. These doses were referenced from doses proven to improve hyperlipidemia in previous studies (X et al., 2018; Y et al., 2019). These doses fall within the range generally used in preclinical studies and were selected to evaluate the effects at intermediate and high doses. Furthermore, they were reasonably set at a level that allows for conversion to human equivalent doses (HED) (Reed et al., 2017). Each group was configured as follows, and the dose of the orally administered extracts was adjusted daily based on the animals' body weight.

[0095] 1) Normal Control Group (NCG): Animals fed a standard diet and orally administered distilled water

[0096] 2) Hyperlipidemia Control Group (HCG): Animals fed a high-fat diet and orally administered distilled water

[0097] 3) Low-dose ginger juice group (GJTG 1): Animals fed a high-fat diet and orally administered 250 mg / kg of ginger juice

[0098] 4) High-dose ginger juice administration group (GJTG 2): Animals fed a high-fat diet and orally administered 500 mg / kg of ginger juice

[0099] 5) Low-dose lemon juice group (LJTG 1): Animals fed a high-fat diet and orally administered 250 mg / kg of lemon juice

[0100] 6) High-dose lemon juice group (LJTG 2): Animals fed a high-fat diet and orally administered 500 mg / kg of lemon juice

[0101] 7) Low-dose mixed solution group (FTG 1): Animals fed a high-fat diet and orally administered 250 mg / kg of a mixed preparation of ginger juice and lemon juice.

[0102] 8) High-dose mixed solution group (FTG 2): Animals fed a high-fat diet and orally administered 500 mg / kg of a mixed preparation of ginger juice and lemon juice.

[0103] 9) Drug Control Group (ATG): Animals fed a high-fat diet and orally administered atorvastatin (10 mg / kg)

[0104]

[0105] 1-5. Analysis of Plasma Lipid Parameters

[0106] (1) Blood sample collection and animal anesthesia

[0107] Blood samples were collected via retroorbital hemorrhage as a terminal procedure of the animals. During the collection process, the animals were anesthetized by intraperitoneal injection of a mixture of ketamine (100 mg / kg) and xylazine (5 mg / kg).

[0108] (2) Analysis of plasma lipid parameters

[0109] Lipid parameters such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured using the following two methods.

[0110] - Automated analysis: Measurements were taken using the "COBAS INTEGRA® 400 Plus" automated equipment provided by "ROCHE®" at CHU Mohamed VI Hospital in Oujda.

[0111] - Manual analysis: Manual measurement using an analysis kit provided by the Biochemistry Laboratory of the Oujda Faculty of Science.

[0112] (3) Total cholesterol measurement

[0113] Total cholesterol was determined based on an enzymatic reaction measuring free cholesterol and esterified cholesterol. Esterified cholesterol is converted to cholesterol by cholesterol esterase. The converted cholesterol is converted by cholesterol oxidase to produce cholest-4-en-3-one and hydrogen peroxide (H2O2), and the generated H2O2 is oxidized to pink-colored quinoneimine in the presence of 4-amino-antipyrine and peroxidase. Finally, the absorbance of the resulting dye was measured at 510 nm.

[0114] (4) Triglyceride measurement

[0115] Plasma triglycerides were measured via an enzymatic reaction. Triglycerides are hydrolyzed by the action of lipoprotein lipase to produce glycerol. The generated glycerol is oxidized by glycerol oxidase to produce H2O2. The generated H2O2 reacted in the same manner as in the measurement of total cholesterol, and its absorbance was measured at 520 nm.

[0116] (5) Calculation of Atherogenic Index of Plasma (AIP)

[0117] The plasma atherosclerotic index is calculated using the logarithm of the ratio of triglyceride (TG) to HDL concentrations. The formula for calculating AIP is shown in Equation 1 below.

[0118] [Mathematical Formula 1]

[0119] AIP=log([Triglycerides] / [HDL])

[0120]

[0121] 1-6. Liver Lipid Parameters

[0122] (1) Liver lipid extraction

[0123] To measure liver lipid content, liver samples were obtained by sacrificing fasting mice that had been treated for 12 weeks after the end of the analysis. Each sample was prepared from various parts of the liver, and lipids were extracted.

[0124] For lipid extraction, 1 g of liver tissue was collected, placed in 10 mL of isopropanol, and left in a beaker at 4 °C for 48 hours. Afterward, the mixture was homogenized under magnetic stirring and then centrifuged at 2500 rpm for 15 minutes. The supernatant was separated and used for liver lipid profile analysis. The results were expressed as total cholesterol (TC) or triglyceride (TG) content (mg) per 1 g of liver tissue.

[0125] (2) Measurement of cholesterol and triglyceride content

[0126] The total cholesterol and triglyceride content of lipids extracted from the liver was measured. First, 10 μL of the supernatant was added to 1 mL of total cholesterol or triglyceride analysis reagent.

[0127] The mixture was incubated by shaking at 37°C for 5 minutes. Afterward, the absorbance of total cholesterol was measured at 510 nm and triglycerides at 520 nm. The TG and TC levels of liver tissue were calculated by applying the same plasma lipid parameter analysis protocol described earlier.

[0128]

[0129] 1-7. Fecal Lipid Parameters

[0130] (1) Extraction of fecal lipids

[0131] Fecal samples collected from fasting experimental animals were dried at 60°C, weighed, and ground into uniform particles. To 1 g of ground feces, 5 mL of standard saline and 5 mL of a chloroform-methanol (2:1, v / v) mixture were added. Subsequently, the mixture was centrifuged and the supernatant was separated. The separated supernatant was dried at 50°C and then dissolved in ethanol to extract fecal lipids.

[0132] (2) Measurement of cholesterol and triglyceride content

[0133] The cholesterol and triglyceride content in the feces was measured according to the process of Examples 1-6 above.

[0134]

[0135] 1-8. Histopathological analysis of the mouse aorta

[0136] Mouse aortic tissue was collected and fixed in a 10% buffered formalin solution for 24 hours. Subsequently, the fixed aortic samples were transferred to 10% physiological saline to verify sample size and adequacy. Tissue blocks were prepared from the fixed aortic samples, placed in a cassette, and immersed in kerosene using an automated tissue processor. Then, tissue sections 4–6 μm thick were cut using a standard microtome. The cut tissue sections were stained with hematoxylin and eosin and mounted between a slide and a coverslip using mounting media. Histopathological changes in the stained tissue slides were examined using an optical microscope (Olympus Corp., Tokyo, Japan).

[0137]

[0138] <Example 2> Analysis Results

[0139] 2-1. Analysis of Total Polyphenol Content and Total Flavonoids

[0140] According to Examples 1-1 and 1-2 above, the total polyphenol content and total flavonoid content contained in ginger juice and lemon juice were analyzed. The analysis results are shown in Table 1 below.

[0141] Total Polyphenols (mg GAE / g Extract) Total Flavonoids (mg QE / g Extract) Ginger Juice 18.48 ± 1.14 7.26 ± 2.05 Lemon Juice 25.23 ± 1.54 12.75 ± 2.10

[0142]

[0143] 2-2. Qualitative and Semi-Quantitative Analysis of a Mixture of Ginger Juice and Lemon Juice

[0144] According to Examples 1-3 above, the content of compounds in ginger juice was analyzed by quantitative and semi-quantitative analysis of phenolic compounds in ginger juice. The analysis results are shown in Table 2 below. Three active ingredients were identified in ginger juice, and four active ingredients were identified in lemon juice.

[0145] (a) Peak Number Compound Residue Time (min) % Area 14-Gingerol 3.97 0.8126-Zingediol 6.41 0.1936-Gingerol 21.60 15.22 (b) Peak Number Compound Residue Time (min) % Area 1-Eriodictiol 9.17 3.122-Rutin 13.25 5.693-Hesperidin 16.31 13.884-Isorhamnetin 18.23 18.43

[0146]

[0147] 2-3. Analysis of Plasma Lipid Parameters

[0148] According to Examples 1-4 above, 90 mice were divided into 9 groups and administered a high-fat diet, ginger juice, or lemon juice, and plasma lipid parameters were analyzed according to Examples 1-5 above. The analysis results are shown in Figure 1. Looking at Figure 1, for the GJTG 1 and LJTG 1 groups, total cholesterol (TC) and triglyceride (TG) levels improved over time compared to the HCG group, but the difference was not significant. However, GJTG 2 and LJTG 2 consistently showed lower total cholesterol (TC) and triglyceride (TG) levels compared to the HCG group. In addition, for the FTG 1 and FTG 2 groups, total cholesterol (TC) and triglyceride (TG) levels improved over time compared to the HCG group, and showed lower TC and TG levels compared to the GJTG 2 and LJTG 2 groups. In particular, the TG levels in the FTG 2 group were found to be lower compared to the positive control group, the ATG group, confirming that ginger juice and lemon juice have a significant effect in improving triglyceride levels.

[0149] In addition, HDL, LDL, and AIP values ​​were measured and calculated for nine mouse groups according to Examples 1-5 above. Figure 2 shows the HDL, LDL, and AIP values. The HCG group, fed a hyperlipidemia diet, showed significantly lower HDL levels and significantly higher LDL levels compared to the control group, NCG. However, the GJTG 1, GJTG 2, LJTG 1, LJTG 2, FTG 1, and FTG 2 groups showed higher HDL levels and lower LDL levels compared to the HCG group, confirming that HDL and LDL levels improved with lemon juice or ginger juice treatment. In particular, the FTG 2 group showed higher HDL levels and lower LDL levels compared to the positive control group, ATG, confirming that combined treatment with ginger juice and lemon juice exhibits activity that significantly improves HDL and LDL levels. In the case of the AIP index, the GJTG 1, GJTG 2, LJTG 1, LJTG 2, FTG 1, FTG 2, and ATG groups showed significantly lower AIP levels compared to the HCG group, and in particular, the FTG 2 group showed significantly lower AIP levels compared to the other groups, confirming that the combined treatment of ginger juice and lemon juice exhibits activity that improves AIP levels.

[0150] Through the above results, it was confirmed that when ginger juice and lemon juice are used in combination, they exhibit significant activity in improving plasma lipid indicators compared to when ginger juice and lemon juice are used individually.

[0151]

[0152] 2-4. Analysis of Hepatic Lipid Parameters

[0153] Lipids were extracted from the livers of mice treated for 12 weeks according to Examples 1-6 above, and total cholesterol (TC) and triglyceride (TG) levels in the liver were measured. The measurement results are shown in Figure 3. In the HCG group fed a high-fat diet, TC and TG levels were found to increase significantly compared to the control group, NCG. However, in the GJTG 1, GJTG 2, LJTG 1, and LJTG 2 groups, TC and TG levels were lower compared to the HCG group, and in the FTG 1 and FTG 2 groups, low TC levels similar to those of the positive control group, ATG, and low TG levels compared to the ATG group. Through these results, it was confirmed that ginger juice and lemon juice each exhibit activity in improving liver lipid indicators, and that when ginger juice and lemon juice are administered in combination, they exhibit significant activity in improving liver lipid indicators due to a synergistic effect.

[0154]

[0155] 2-5. Analysis of Fecal Lipid Parameters

[0156] According to Examples 1-7 above, lipids were extracted from fecal samples collected from nine mouse groups, and the total cholesterol (TG) index was measured. The measurement results are shown in Figure 4. It was found that the excretion of fecal cholesterol in the groups treated with ginger juice (GJTG 1 and GJTG 2) and lemon juice (LJTG 1 and LJTG 2) was significantly increased compared to the HCG group. In particular, the GJTG 2 and LJTG 2 groups showed improved excretion rates of +25.84% (p < 0.01) and +22.71%, respectively, indicating that the fecal cholesterol level increased as the concentration of ginger juice and lemon juice increased. In addition, the FTG 1 and FTG 2 groups, which were administered ginger juice and lemon juice together, showed the most significant improvement effects with +26.13% (p < 0.01) and +38.68% (p < 0.001), respectively, and showed significantly higher fecal cholesterol content compared to the positive control group ATG (+12.22%; p < 0.05).

[0157] Through the above results, it was confirmed that ginger juice and lemon juice each possess activity that significantly increases cholesterol excretion in feces, and that when ginger juice and lemon juice are administered in combination, the activity of significantly increasing fecal cholesterol excretion in a hyperlipidemia model is further enhanced due to their synergistic effect.

[0158]

[0159] 2-6. Histopathological analysis of mouse aorta

[0160] Aortic tissues were collected from mice treated for 12 weeks according to Examples 1-8 above, and histopathological changes were analyzed. Figure 5 shows microanatomical images of histological sections of the mouse aorta.

[0161] In the aorta of the hyperlipidemia control group (HCG), an increase in fatty pores within muscle cells was observed along with excessive lipid deposition compared to the normal control group (NCG). Additionally, due to pathological changes in the intima-endothelium structure, the thickness of the tunica-endothelium layer was found to have significantly increased from 58.2 μm in the NCG group to 70.4 μm in the HCG group.

[0162] In the groups administered ginger juice (GJTG 1 and GJTG 2), lemon juice (LJTG 1 and LJTG 2), and ginger and lemon juice preparations (FTG 1 and FTG 2) at doses of 250 mg / kg and 500 mg / kg, respectively, a reduction in lipid deposition in the aorta and an improvement in intima-thickness were observed compared to the HCG group. The tunica-intima-thickness of each group was measured as follows.

[0163] GJTG 1: 65.72 μm, GJTG 2: 61.13 μm, LJTG 1: 66.05 μm, LJTG 2: 62.87 μm, FTG 1: 61.91 μm, FTG 2: 59.11 μm

[0164] In the case of the combination of ginger and lemon juice (FTG 2), the tunica-endometrium thickness was 59.11 μm, showing an improvement effect similar to that of the atorvastatin (ATG; 10 mg / kg administration) group (58.98 μm).

[0165] Through the above results, it was confirmed that ginger juice and lemon juice each possess activity that inhibits lipid deposition in the aorta and improves pathological changes, and that when ginger juice and lemon juice are administered in combination, pathological changes in the aorta can be improved more effectively due to the synergistic effect between them.

[0166]

[0167] 2-7. Analysis of binding energies between molecules in ginger and lemon juice interacting with target receptors

[0168] To evaluate the interaction with the target receptor 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), the binding energies of various molecules were measured to analyze the potential of molecules present in ginger and lemon as inhibitors. The binding energies for 4-gingerol, 6-gingerol, 6-zingediol, eriodictiol, hesperidin, isorhamnetin, rutin, and the reference molecule quercetin were measured, and the results are shown in Figure 6. Looking at Figure 6, the values ​​were 4-gingerol (-5.1), 6-gingerol (-5.5), 6-zingediol (-5.6), eriodictiol (-7.5), hesperidin (-9.4), isorhamnetin (-7.2), rutin (-7.9), and the reference molecule quercetin (-7.7). Hesperidin exhibited the highest binding affinity at -9.4 kcal / mol, confirming that its interaction with the target receptor is very strong. Rutin showed a higher binding affinity at -7.9 kcal / mol than quercetin (-7.7 kcal / mol), indicating that its interaction strength with the receptor is superior to that of quercetin. Eriodictiol (-7.5 kcal / mol) and isorhamnetin (-7.2 kcal / mol) showed binding affinities similar to those of quercetin. On the other hand, gingerol (4-gingerol and 6-gingerol) and 6-zingediol exhibited binding energies of -5.1 to -5.6 kcal / mol, respectively, showing relatively low interaction strengths with the target receptor; this confirms that gingerol derivatives have lower inhibitory activity compared to quercetin and other molecules.

[0169] Through the above results, it was confirmed that eriodictiol, hesperidin, isorhamnetin, and rutin present in ginger and lemon exhibit lower binding energy compared to quercetin, showing strong binding affinity with the target receptor 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), and that compounds derived from ginger and lemon can improve lipid indicators by inhibiting the activity of the target receptor.

[0170]

[0171] 2-8. Analysis of Molecular Physicochemical and Pharmacokinetic Properties in Ginger and Lemon Juice

[0172] To confirm the physicochemical properties and pharmacokinetic potential of molecules in ginger and lemon juice, radar plot analysis was performed on 4-gingerol, 6-gingerol, 6-zingediol, eriodictiol, hesperidin, isorhamnetin, and rutin. The results of the radar plot analysis are shown in Figure 7.

[0173] The radar plot of 4-gingerol exhibited superior characteristics across key parameters such as lipophilicity, size, polarity, solubility, flexibility, and saturation. Balanced lipophilicity and polarity support efficient membrane permeability, providing excellent absorption capacity, while flexibility and solubility indicate the optimization of the molecule's in vivo absorption and distribution. The radar plot of 6-gingediol was similar to the profile of 4-gingerol but showed slight differences in polarity and flexibility. Increased polarity somewhat reduces lipid membrane permeability and affects absorption and distribution efficiency; conversely, maintaining flexibility preserves metabolic stability, but the increase in polarity indicates that overall pharmacokinetic performance is affected. The radar plot of 6-gingerol displayed physicochemical properties very similar to those of 4-gingerol. Although there are slight differences in solubility and polarity, these differences have a limited impact on pharmacokinetic behavior; increased polarity has a minimal effect on membrane permeability, and differences in solubility result in slight variations in absorption rates. In the case of isorhamnetin, unlike gingerol compounds, the radar plot of isorhamnetin showed high polarity and solubility. Increased polarity indicates that bioavailability is limited due to reduced membrane permeability, while high solubility indicates that absorption in an aqueous environment can compensate for reduced lipophilicity. Furthermore, increased polarity indicates that the molecular clearance rate is accelerated, allowing for rapid elimination from systemic circulation. The in silico prediction results based on radar plot analysis were found to be consistent with the lipid-lowering effects of ginger juice and lemon juice, respectively, confirmed in the above examples. In the above examples, the formulation combining ginger juice and lemon juice exhibited a synergistic effect; this synergy can be confirmed to be due to the mutually complementary bioavailability and distribution characteristics of the active ingredients within ginger juice and lemon juice, as shown in the radar plots of ginger juice and lemon juice.It was confirmed that the high polarity and solubility of compounds such as isorhamnetin in lemons, combined with the lipophilic and permeable properties of gingerol compounds, enhance overall pharmacokinetic performance, thereby causing a synergistic effect between ginger juice and lemon juice.

[0174]

[0175] In addition, to confirm the gastrointestinal absorption and blood-brain barrier (BBB) ​​permeability of molecules in ginger juice and lemon juice, a Boiled Egg Test analysis was performed on 4-gingerol, 6-gingerol, 6-zingediol, eriodictiol, hesperidin, isorhamnetin, and rutin. The results of the Boiled Egg Test analysis are shown in Figure 8.

[0176] 4-gingerol is absorbed very efficiently from the gastrointestinal tract, but its potential to cross the blood-brain barrier (BBB) ​​appears limited; this confirms that while systemic bioavailability is high, its impact on the central nervous system is minimal. 6-gingediol also exhibits gastrointestinal absorption and BBB penetration characteristics similar to 4-gingerol. Despite slight differences in polarity and solubility, the two compounds showed similar ability to enter systemic circulation, yet their impact on the central nervous system was found to be limited. 6-gingerol also displayed gastrointestinal absorption capacity and limited brain penetration characteristics similar to other gingerol compounds, indicating that ginger-derived bioactive compounds act primarily in the periphery. On the other hand, eriodictiol demonstrated a high gastrointestinal absorption rate and moderate BBB penetration potential, suggesting potential to exert effects in both the periphery and the central nervous system. Hesperidin exhibited low gastrointestinal absorption and limited brain penetration, indicating low systemic and central bioavailability. Isorhamnetin, known as a highly polar compound, exhibited pharmacokinetic characteristics similar to gingerol compounds in that it showed good gastrointestinal absorption but limited cerebral penetration. Rutin showed low levels of both gastrointestinal absorption and cerebral penetration, indicating limited systemic and central pharmacokinetic potential. These results of the in silico analysis based on the Boiled Egg Test are consistent with the hyperlipidemia-improving effects of ginger and lemon juice confirmed in the aforementioned examples. In particular, the excellent gastrointestinal absorption capacity of gingerol compounds correlates with high systemic bioavailability, and considering its limited BBB crossing, it suggests that its primary mechanism of action is likely exerted through pathways affecting lipid metabolism in the liver and other peripheral tissues.

[0177] In addition, the formulation combining ginger juice and lemon juice exhibited a more enhanced lipid-lowering effect than the individual extracts. This synergistic effect was attributed to the complementary bioavailability profiles of the active compounds in ginger juice and lemon juice, as confirmed in the Boiled Egg Test. It was confirmed that the potent gastrointestinal absorption capacity of gingerol compounds and the complementary absorption characteristics of lemon-derived compounds, such as eriodictiol, enhance systemic efficacy, thereby inducing a more potent pharmacological response.

[0178]

[0179] Through the above examples, the activity of ginger juice and lemon juice in improving lipid levels in plasma, lipid levels in the liver, and lipid levels in the feces, and the activity of inhibiting lipid depletion in the aorta were analyzed, and the activity of the active ingredients in ginger juice and lemon juice as inhibitors on target receptors, as well as physicochemical and pharmacokinetic properties, were analyzed to confirm the use of ginger juice and lemon juice for the prevention or treatment of hyperlipidemia.

Claims

1. A food composition for the prevention or improvement of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

2. In Paragraph 1, The above mixture is a food composition obtained by mixing ginger juice and lemon juice in a weight ratio of 1:

1.

3. In Paragraph 1, A composition in which the above ginger juice comprises 4-gingerol, 6-gingerol, or 6-gingediol as a component.

4. In Paragraph 1, A composition in which the above lemon juice comprises eriodictyol, hesperidin, isorhamnetin, or rutin as a component.

5. In Paragraph 1, The above mixture is a composition that reduces the total cholesterol or triglyceride content in the plasma.

6. In Paragraph 1, The above mixture is a composition that increases the total cholesterol or triglyceride content in feces.

7. In Paragraph 1, The above mixture is a composition that reduces lipid deposition in the aorta.

8. In Paragraph 1, The above mixture is a composition that reduces the thickness of the aortic intima.

9. In Paragraph 3, A composition in which the above 4-gingerol has a binding energy of -5.1 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA).

10. In Paragraph 3, A composition in which the above 6-gingerol has a binding energy of -5.5 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA).

11. In Paragraph 3, A composition in which the above 6-gingediol has a binding energy of -5.6 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA).

12. In Paragraph 4, A composition in which the above eriodictyol has a binding energy of -7.5 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA).

13. In Paragraph 4, A composition in which the hesperidin above has a binding energy of -9.4 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA).

14. In Paragraph 4, A composition in which the above isorhamnetin has a binding energy of -7.2 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA).

15. In Paragraph 4, A composition in which the above rutin has a binding energy of -7.9 kcal / mol with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA).

16. In Paragraph 1, A composition wherein the above lipid-related metabolic disease is one or more selected from the group consisting of diabetes, hyperlipidemia, fatty liver, hepatitis, cirrhosis, arteriosclerosis, hypertension, cardiovascular disease, and metabolic syndrome in which the above diseases occur simultaneously.

17. A health functional food composition for the prevention or improvement of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

18. A pharmaceutical composition for the prevention or treatment of lipid-related metabolic diseases comprising a mixture of ginger (Zingiber officinale) juice and lemon (Citrus limon) juice as an active ingredient.

19. A method for preventing or treating lipid-related metabolic diseases comprising the step of administering the composition of claim 18 to an individual.

Images