Composition Comprising the Extract of Pteridium aquilinum for Inhibiting Advanced Glycation End Products

Abstract

The present invention relates to a food composition for inhibiting the formation of advanced glycation end products or inhibiting, cutting, or degrading the cross-linking of advanced glycation end products, comprising a fern extract as an active ingredient; a food composition and a health functional food for preventing or improving advanced glycation end product-related diseases, regulating blood pressure, improving cholesterol, improving joint or bone health, regulating blood sugar, improving blood triglycerides, improving skin condition, antioxidant, or anti-inflammatory purposes, comprising a fern extract as an active ingredient; and a pharmaceutical composition for preventing or treating advanced glycation end product-related diseases, comprising a fern extract as an active ingredient. The bracken extract according to the present invention exhibits excellent activity in the formation and accumulation of advanced glycation end products, and also shows effects of inhibiting, cleaving, and degrading the cross-linking of advanced glycation end products and collagen. Therefore, a composition containing the bracken extract can be used not only for inhibiting the formation of advanced glycation end products or for inhibiting, cleaving, or degrading the cross-linking of advanced glycation end products, but can also be usefully employed in the manufacture of foods and pharmaceuticals for the prevention, improvement, or treatment of diseases caused by advanced glycation end products.

Description

Technology Field

[0001] The present invention relates to a food composition for inhibiting the formation of advanced glycation end products or inhibiting, cutting, or degrading the cross-linking of advanced glycation end products, comprising a bracken extract as an active ingredient; a food composition and health functional food for preventing or improving advanced glycation end product-related diseases, regulating blood pressure, improving cholesterol, improving joint or bone health, regulating blood sugar, improving blood triglycerides, improving skin condition, antioxidant, or anti-inflammatory purposes, comprising a bracken extract as an active ingredient; a pharmaceutical composition for preventing or treating advanced glycation end product-related diseases, comprising a bracken extract as an active ingredient; a quasi-drug composition for improving, preventing, or treating advanced glycation end product-related diseases, comprising a bracken extract as an active ingredient; and a feed composition for preventing or improving advanced glycation end product-related diseases, comprising a bracken extract as an active ingredient. Background Technology

[0002] Glycation is a non-enzymatic reaction in which the carbonyl group of a reducing sugar, such as glucose or fructose, reacts with the N-terminal amino group of a protein or the ε-amino group of lysine to form a Schiff base, and through a series of complex reactions such as condensation, re-translocation, oxidation, cleavage, and cyclization, forms brown, irreversible advanced glycation end-products (AGEs).

[0003] Once formed, these irreversible reaction products, known as Advanced Glycation Products (AGEs), are not broken down even after blood glucose levels return to normal; instead, they accumulate in tissues and cause abnormal changes to their structure and function. For instance, AGEs form cross-links with collagen and other substances, leading to abnormal changes in bodily structures and other protein-connected tissues.

[0004] Thus, advanced glycation end products are known to be involved in the development of various diseases by causing abnormal changes within the body. In particular, many studies have reported that advanced glycation end products are closely associated with the progression of various aging-related diseases, such as diabetic complications, arteriosclerosis, end-stage renal failure, rheumatoid arthritis, Alzheimer's disease, and skin wrinkle formation (Semin Nephrol. 2007 Mar;27(2):130-43; and Curr Alzheimer Res. 2004 Feb;1(1):39-46).

[0005] Accordingly, research and development are being attempted on materials that can inhibit the formation of advanced glycation end products or break down already formed advanced glycation end product crosslinks, and developed advanced glycation end product inhibitors include aminoguanidine and ALT-711.

[0006] Aminoguanidine, a synthetic drug, is a nucleophilic hydrazine that binds to the products of condensation reactions to inhibit the formation of advanced glycation end products, thereby preventing the progression to complications, and ALT-711 is a nucleophilic substance that attacks the electrophilic dicarbonyl groups of already formed advanced glycation end product crosslinks to break down the crosslinks of the advanced glycation end products.

[0007] However, most conventional advanced glycation end product (AGE) inhibitors are synthetic compounds that cause adverse effects in the body, raising safety concerns regarding long-term use; therefore, there is a need to develop materials based on natural substances that do not cause such side effects.

[0008] Meanwhile, bracken ( Pteridium aquilinum Bracken is a perennial plant belonging to the fern family and is used for food; it is known to be eaten cooked, raw, salted, or dried. It is rich in fiber and contains large amounts of vitamin C, vitamin B2, and calcium. In particular, it is rich in calcium, which is beneficial for growing children and the elderly, and it is rich in iron, which is known to be good for people with anemia or pregnant women. However, research on the physiological activity of bracken is still lacking, and there have been no reports on the inhibitory activity of bracken extracts on advanced glycation end products.

[0009] Against this background, the inventors have completed the present invention by identifying that the fern extract has the efficacy of inhibiting the formation of advanced glycation end products and simultaneously inhibiting and cleaving the cross-linking between the advanced glycation end products and collagen, thereby confirming that the fern extract can be used as a material for food compositions and pharmaceutical compositions for the prevention, improvement, or treatment of diseases related to advanced glycation end products. Prior art literature

[0010] Republic of Korea Published Patent No. 10-2013-0113626 The problem to be solved

[0011] The object of the present invention is to provide a food composition for inhibiting the formation of advanced glycation end products comprising a fern extract as an active ingredient; or for inhibiting, cutting, or degrading the cross-linking of advanced glycation end products.

[0012] Another objective of the present invention is to provide a food composition for the prevention or improvement of diseases related to advanced glycation end products; for blood pressure control; for cholesterol improvement; for joint or bone health improvement; for blood sugar control; for blood triglyceride improvement; for skin condition improvement; for antioxidant; or for anti-inflammatory purposes, comprising a fern extract as an active ingredient; and to provide a health functional food comprising said composition.

[0013] Another objective of the present invention is to provide a pharmaceutical composition for the prevention or treatment of advanced glycation end product-related diseases comprising a fern extract as an active ingredient.

[0014] Another objective of the present invention is to provide a quasi-drug composition for the improvement, prevention, or treatment of diseases related to advanced glycation end products, comprising a fern extract as an active ingredient.

[0015] Another objective of the present invention is to provide a feed composition for the prevention or improvement of diseases related to advanced glycation end products, comprising a fern extract as an active ingredient. means of solving the problem

[0017] This is explained in detail as follows. Meanwhile, each description and embodiment disclosed in this application may be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in this application fall within the scope of this application. Furthermore, the scope of this application should not be considered limited by the specific descriptions provided below.

[0018] The inventors completed the present invention by confirming that the fern extract of the present invention inhibits the formation of advanced glycation end products and simultaneously inhibits and cleaves the cross-linking between advanced glycation end products and collagen, as confirmed in the examples and experimental examples below.

[0019] As one embodiment for achieving the above objective, the present invention provides a food composition for inhibiting the formation of advanced glycation end products comprising a fern extract as an active ingredient; or a food composition for inhibiting, cutting, or degrading cross-linking of advanced glycation end products; and a health functional food comprising said food composition.

[0020] The term "fern" of the present invention Pteridium aquilinum Ferns are perennial plants belonging to the fern family and are used for food. They are known to be eaten cooked, raw, salted, or dried. They are rich in fiber and contain large amounts of Vitamin C, Vitamin B2, and calcium. In particular, they are rich in calcium, which is beneficial for growing children and the elderly. They are also rich in iron, which is known to be good for people with anemia and pregnant women.

[0021] The term "extract" in the present invention includes the extract itself and all formulations of extracts that can be formed using the extract, such as an extract obtained by the extraction treatment of the fern, a diluted or concentrated extract of the extract, a dried product obtained by drying the extract, a modified or purified extract of the extract, or a mixture thereof.

[0022] The method for extracting the extract of the present invention is not particularly limited and can be extracted according to methods commonly used in the relevant technical field. Non-limiting examples of the extraction method include hot water extraction, cold maceration extraction, solvent extraction, steam distillation, elution, pressing, ultrasonic extraction, filtration, and reflux extraction, and these may be performed individually or in combination of two or more methods.

[0023] The extract of the present invention is extracted from a fern using a suitable solvent and may include, for example, a crude extract, an extract soluble in a polar solvent, or an extract soluble in a non-polar solvent. The type of extraction solvent used to prepare the extract is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent include water; lower alcohols with 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropanol, butanol, propyl alcohol, butyl alcohol; polyhydric alcohols such as glycerin, butylene glycol, propylene glycol; hydrocarbon solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, dichloromethane; or mixtures thereof. Specifically, the extraction solvent may be ethanol. Additionally, a solvent extract may be prepared by extracting one or more times using the solvent.

[0024] Specifically, in the present invention, the bracken extract may be obtained by drying and grinding bracken, adding 30 to 90% fermented alcohol to the bracken powder, and extracting at a temperature of 30 to 70°C. More specifically, it may be obtained by adding 50 to 70% fermented alcohol to the bracken powder and extracting at a temperature of 40 to 60°C. The extract of the present invention may be used as is after filtration to remove suspended solid particles, such as by filtering particles using nylon or a freeze-filtration method, or it may be dried using freeze-drying, hot-air drying, spray drying, etc. Additionally, the extract may undergo a conventional fractionation process and may be purified using a conventional purification method.

[0025] Specifically, in the present invention, bracken may be extracted with a fermented alcohol ethanol solvent, the extract may be filtered through filter paper, concentrated under reduced pressure, and freeze-dried for use, but is not limited thereto.

[0026] The term "active ingredient" in the present invention refers to a component that exhibits the intended activity alone, or can exhibit activity together with a carrier that is inactive itself.

[0027] The term "advanced glycation product" in the present invention refers to a substance formed through various processes by glycation, in which proteins and sugars react. The glycation reaction occurs almost naturally without an energy supply and has the characteristic of being irreversible after a certain stage in food or the body. In the body, it reacts with various protein components such as glucose in the blood, its breakdown products, hemoglobin, LDL, and collagen to produce various types of advanced glycation products. Once formed, these advanced glycation products are not broken down even if blood sugar levels return to normal, and they accumulate in the blood or tissues for the duration of the protein's lifespan. It is known that accumulated advanced glycation products interact with advanced glycation product receptors, leading to the accumulation of inflammatory cells, increased secretion of growth-promoting cytokines and apoptosis, and abnormal changes in the structure and function of tissues during the protein's lifespan, thereby causing various diseases such as metabolic diseases, diabetes, diabetic complications, Alzheimer's disease, atherosclerosis, uremia, microvascular disease, macrovascular disease, cataracts, Parkinson's disease, aging, or cancer.

[0028] The food composition of the present invention may include the fern extract in various amounts, provided that it has the effect of inhibiting the formation of advanced glycation end products, or inhibiting, cutting, or degrading the cross-linking of advanced glycation end products.

[0029] In addition to the bracken extract, the food composition of the present invention may further include any compound or natural extract known in the art to have its safety verified and possess the corresponding activity in order to enhance convenience of taking or consuming.

[0030] These compounds or extracts may include compounds or extracts listed in pharmacopoeias of each country (the 'Korean Pharmacopoeia' in Korea), health functional food codes of each country (the 'Standards and Specifications for Health Functional Foods' notified by the Ministry of Food and Drug Safety in Korea), compounds or extracts that have received product approval in accordance with the laws of each country regulating the manufacture and sale of pharmaceuticals (the 'Pharmaceutical Affairs Act' in Korea), and compounds or extracts whose functionality has been recognized in accordance with the laws of each country regulating the manufacture and sale of health functional foods (the 'Act on Health Functional Foods' in Korea).

[0031] The term "food" in the present invention includes meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, nutritional supplements, functional foods, food additives, health functional foods, and health foods, and includes all foods in the conventional sense.

[0032] The aforementioned "health food" refers to a food that has active effects of maintaining or promoting health compared to general food, and "health supplement food" refers to a food intended for the purpose of health support. Depending on the context, the terms "health functional food," "health food," and "health supplement food" are used interchangeably.

[0033] The term "health functional food" in this invention is synonymous with "food for special health use (FosHU)," and refers to a food with high medical or therapeutic effects that is processed to efficiently exhibit bio-regulatory functions in addition to nutritional supply. Here, "functionality" refers to obtaining useful effects for health purposes, such as regulating nutrients or physiological actions regarding the structure and function of the human body. The food of this invention can be manufactured by methods commonly used in the industry, and during such manufacturing, raw materials and ingredients commonly added in the industry may be added. Furthermore, the formulation of the food can be manufactured without restriction as long as it is a formulation recognized as a food. The food composition of this invention can be manufactured in various forms of formulations. Unlike general pharmaceuticals, it has the advantage of being made from food ingredients, thus avoiding side effects that may occur with long-term use of pharmaceuticals, and it is highly portable. Therefore, the food of this invention can be consumed as an adjuvant for reducing Advanced Glycation End Products (AGEs) in the body by inhibiting their formation, inhibiting the cross-linking of AGEs, or cleaving the cross-links of AGEs.

[0034] Specifically, the above-mentioned health functional food is a food made by adding fern extract to food materials such as beverages, teas, spices, chewing gum, and confectionery, or by manufacturing it into pills, tablets, capsules, powders, or suspensions, and means that consuming it brings about specific health effects. However, unlike general medicines, it has the advantage of not having side effects that may occur when taking medicine for a long period of time because it is made from food.

[0035] The food composition of the present invention is very useful because, since it can be consumed on a daily basis, it is possible to expect effects such as inhibiting the formation of advanced glycation end products, inhibiting the cross-linking of advanced glycation end products, or reducing advanced glycation end products in the body through the cleavage of cross-linking of advanced glycation end products.

[0036] The food composition of the present invention may be manufactured in any form, for example, as beverages such as tea, juice, carbonated beverages, and isotonic drinks; processed dairy products such as milk and yogurt; food products such as chewing gum, rice cakes, Korean confectionery, bread, confectionery, and noodles; and formulations such as tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, and bars. Furthermore, the food composition of the present invention may take on any product classification in terms of legal and functional classification, as long as it complies with the regulations in effect at the time of manufacture and distribution. For example, it may be a health functional food under the Korean 'Act on Health Functional Foods', or a confectionery, tea, beverage, or special dietary food according to each food type in the Food Code of the Korean 'Food Sanitation Act' (Notification of the Ministry of Food and Drug Safety 'Standards and Specifications for Food').

[0037] In addition, the food composition of the present invention may include food additives in addition to its active ingredients. Food additives can generally be understood as substances added to, mixed with, or permeated into food during its manufacture, processing, or preservation; since they are consumed daily and over a long period along with food, their safety must be guaranteed. In terms of use, such food additives are classified into sweeteners, flavor enhancers, preservatives, emulsifiers, flavorings, etc.

[0038] The above sweeteners are used to impart a suitable sweetness to food, and may be natural or synthetic. For example, sweeteners such as neotame, lactitol, D-ribose, mannitol, D-maltitol, and sodium saccharin may be used.

[0039] The above flavor enhancers are food additives that enhance the taste or aroma of food, and both natural and synthetic ones may be used. For example, flavor enhancers may include disodium 5'-guanylate, L-glutamic acid, glycine, betaine, etc.

[0040] Sodium metabisulfite, sulfur dioxide, sorbic acid, benzoic acid, grapefruit seed extract, etc. may be used as the above preservatives.

[0041] The above emulsifier is a food additive that homogeneously mixes or maintains two or more immiscible phases, such as water and oil, and may include sodium gluconate, glycerin fatty acid ester, lecithin, magnesium stearate, alginic acid, etc.

[0042] The above flavorings are food additives that impart a unique aroma to food or reinforce the original aroma of food lost during the manufacturing process, and may include ethyl vanillin, ethyl octanoate, linalyl acetate, allyl caproate, paramethylacetophenone, etc.

[0043] In addition to the food additives described above, the food composition of the present invention may include physiologically active substances or minerals known in the art and guaranteed to be safe as food additives for the purpose of supplementing and reinforcing functionality and nutritional value. Examples of such physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, vitamin B12, tocopherol, dibenzoylthiamine, etc. Examples of such minerals include calcium preparations such as calcium citrate, magnesium preparations such as magnesium stearate, iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc, etc.

[0044] The food composition of the present invention may include the aforementioned food additives in an appropriate amount to achieve the purpose depending on the product type, and regarding other food additives that may be included in the food composition of the present invention, reference may be made to the food codes or food additive codes of each country.

[0045] When the above-mentioned bracken extract is used as a food additive, it may be added as is or used in combination with other foods or food ingredients, and may be used appropriately according to conventional methods. The mixing amount of the active ingredient may be appropriately determined according to its intended use.

[0047] In another embodiment for achieving the above objective, the present invention provides a food composition comprising a fern extract as an active ingredient for the prevention or improvement of diseases related to advanced glycation end products, for blood pressure control, for cholesterol improvement, for joint or bone health improvement, for blood sugar control, for blood triglyceride improvement, for skin condition improvement, for antioxidant or anti-inflammatory purposes; and a health functional food comprising said food composition.

[0048] The terms "fern," "extract," "active ingredient," "advanced glycation product," "food," and "health functional food" of the present invention are as described above.

[0049] The term "advanced glycation product-related disease" of the present invention may include all diseases that may be caused by advanced glycation products, and is not specifically limited thereto, but may be metabolic diseases, diabetes, diabetic complications, Alzheimer's disease, Parkinson's disease, cancer, chronic kidney disease, heart disease, vascular disease, aging, uremia, or rheumatoid arthritis.

[0050] The above metabolic diseases are a collective term for diseases caused by abnormalities in the metabolism of substances in the body, such as sugars, lipids, proteins, vitamins, and minerals, and may include, but are not limited to, diabetes mellitus, obesity, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, hyperlipidemia, hypertension, and hyperinsulinemia.

[0051] Advanced glycation end products have been reported to cause metabolic dysfunction, diabetes, and obesity by activating inflammatory pathways, inducing oxidative stress, causing impaired mitochondrial oxidative metabolism, promoting insulin resistance, or causing pancreatic β-cell dysfunction (SERGI, Domenico, et al. Molecular Nutrition & Food Research (, 2020), and it was found that the higher the intake of carboxymethyl lysine, a type of advanced glycation end product, the higher the risk of abdominal obesity and dyslipidemia (ANGOORANI, Pooneh, et al. International Journal of Food Sciences and Nutrition , 2016, 67.2: 170-176.).

[0052] In addition, it has been reported that advanced glycation endproducts activate receptors for advanced glycation endproducts (RAGE) present in Kupffer cells and hepatic stellate cells, and that fatty liver exposed to advanced glycation endproducts responds with increased oxidative stress and inflammation, thereby inducing non-alcoholic fatty liver disease (FERNANDO, Dinali H., et al. International journal of molecular sciences , 2019, 20.20: 5037.). In a high-fat, high-fructose, high-cholesterol diet (HFHC) model of non-alcoholic fatty liver disease, it was found that liver damage, non-alcoholic steatohepatitis, and liver fibrosis can be controlled by regulating the intake of advanced glycation end products (LEUNG, Christopher, et al. World journal of gastroenterology , 2016, 22.35: 8026.).

[0053] In addition, many studies have reported that advanced glycation end products are closely associated with the progression of hyperlipidemia, hypertension, and hyperinsulinemia (LIN, Reigh-Yi, et al. Atherosclerosis , 2002, 163.2: 303-311.; and CROFTS, Catherine, et al. Diabesity , 2015, 1.4: 34-43.). For example, advanced glycation end products (AGEs) act directly through receptors to alter the functions of many intracellular and extracellular proteins, including antioxidant and metabolic enzymes, calcium channels, lipoproteins, and transcription and structural proteins; they affect vascular (arterial) structure and function and have been found to cause endothelial dysfunction, inflammation, and oxidative stress, which are characteristics of hypertension and atherosclerosis. Furthermore, a reduction in AGEs has been proven effective in reducing oxidative stress, blood pressure, and atherosclerotic vascular changes (PRASAD, Kailash; MISHRA, Manish. The International journal of angiology: official publication of the International College of Angiology, Inc , 2017, 26.1: 1.; and VASDEV, Sudesh; Gill, Vicki; SINGAL, Pawan. Cell Biochemistry and Biophysics , 2007, 49.1: 48-63.).

[0054] The above-mentioned diabetic complications refer to symptoms caused when diabetes persists for a long period. Since diabetic complications differ from the criteria for onset and diagnosis of diabetes, treatments for diabetic complications are used separately from treatments for diabetes. As the cause of diabetic complications is induced by the abnormal activity of advanced glycation endproducts (AGEs) and aldose reductase, as well as accelerated oxidative stress, substances that inhibit AGEs or inhibit the cross-linking of AGEs with collagen can be used as treatments for diabetic complications. Diseases included in the above-mentioned diabetic complications may include, but are not limited to, diabetic retinopathy, diabetic cataracts, diabetic nephropathy, diabetic neuropathy, diabetic foot ulcers, diabetic heart disease, diabetic osteoporosis, or diabetic arteriosclerosis.

[0055] Protein glycosylation disrupts normal function by destroying molecular conformation, altering enzymatic activity, and interfering with receptor function, and advanced glycation end products are known to contribute to the development of diabetic complications by forming intracellular and extracellular cross-links with other endogenous core molecules, including lipids and nucleic acids, as well as proteins (SINGH, Varun Parkash, et al. The Korean Journal of Physiology & Pharmacology , 2014, 18.1: 1-14.). Specifically, increased protein glycosylation and the accumulation of advanced glycation end products (AGEs) have been studied to activate intracellular signaling pathways and the production of pro-inflammatory and sclerotic cytokines; furthermore, the action of these AGEs has been reported to promote the development and progression of diabetic complications, including diabetic retinopathy, diabetic cataracts, diabetic nephropathy, diabetic neuropathy, diabetic cardiomyopathy, diabetic vascular complications, bone fragility and osteoporosis in diabetic patients, diabetic atherosclerosis, and diabetic myocardial infarction (GOH, Su-Yen; COOPER, Mark E. The Journal of Clinical Endocrinology & Metabolism , 2008, 93.4: 1143-1152.; YAMAMOTO, Masahiro; SUGIMOTO, Toshitsugu. Current osteoporosis reports , 2016, 14.6: 320-326.; MEERWALDT, R., et al. Diabetologia , 2005, 48.8: 1637-1644.; LLAURADΣ, Gemma, et al. J Endocrinol , 2014, 221.3: 405-413.; and BAIDOSHVILI, A., et al. Arteriosclerosis, thrombosis, and vascular biology , 2006, 26.11: 2497-2503.).

[0056] Alzheimer's disease (AD) is the most common degenerative brain disease causing dementia; it typically manifests as a chronic and progressive condition involving multiple impairments in brain functions, including memory, thinking, learning ability, language, and judgment. Advanced glycation end products (AGEs) are associated with Alzheimer's disease because they induce neurodegeneration through interactions with AGE receptors, and research has been conducted on the mechanisms of Alzheimer's disease development involving AGEs (KO, Shun-Yao, et al. PLoS One , 2015, 10.11: e0143345.). For example, the AGE-RAGE axis mediated Aβ through increased cathepsin B and asparagine endopeptidase. 1-42 It has been reported that it causes Alzheimer's disease by increasing the formation and tau phosphorylation (BATKULWAR, Kedar, et al. ACS chemical neuroscience , 2018, 9.5: 988-1000.).

[0057] The aforementioned Parkinson's disease is a chronic, progressive, degenerative brain disease of the nervous system caused by the loss of dopamine neurons, and the role of protein glycosylation in neurodegenerative diseases such as Parkinson's disease has been studied (MIRANDA, Hugo Vicente; OUTEIRO, Tiago Fleming. The Journal of pathology , 2010, 221.1: 13-25.), and it has been reported that drugs that reduce advanced glycation end product (AGE) levels exhibit protective activity in both Parkinson's disease and diabetes (KOENIG, Annekatrin; VICENTE MIRANDA, Hugo; OUTEIRO, Tiago Fleming. Journal of Parkinson's disease , 2018, 8.1: 33-43.).

[0058] The aforementioned cancer is a general term for diseases caused by abnormal cell growth, also known as tumors. The role of the Advanced Glycation End Receptor (RAGE) in various types of cancer has been studied. RAGE has been reported to increase the number of cancer cells and be involved in the progression of various types of cancer and cancer complications by activating cascading pathways, including the activation of cell cycle proteins (e.g., cyclin D1), anti-apoptotic proteins (e.g., BCl2), prosurvival (AKT), and autophagic proteins. It has also been shown to play a crucial role in tissue angiogenesis and to suppress immune responses through the activation of myeloid-derived suppressor cells (MDSCs) (MALIK, Parth, et al. Biochimica et Biophysica Acta (BBA)-General Subjects , 2015, 1850.9: 1898-1904.).

[0059] Chronic kidney disease (CKD) refers to a condition characterized by persistent proteinuria, evidence of kidney damage such as hematuria, or a continuous decline in kidney function for more than three months. Chronic renal failure (CRF) is defined as a condition where kidney function drops to 50% or less and persists for more than three months; it is a narrower term than chronic kidney disease. Subjective symptoms include polyuria, swelling around the eyes and lower extremities, lethargy, easy fatigue, loss of appetite, nausea, skin itching, and bad breath (ammonia-like odor). These symptoms are often accompanied by anemia and hypertension, and children may experience delayed growth and a poor complexion. Research has been conducted on the correlation between advanced glycation end products (AGEs) and chronic kidney disease. Studies have reported that AGEs accumulate in patients with chronic kidney disease, bind to AGE receptors to amplify monocyte disturbances, and contribute to monocyte-mediated systemic inflammation associated with renal failure (LINDEN, Ellena, et al. Clinical Journal of the American Society of Nephrology , 2008, 3.3: 691-698.; and HOU, Fan Fan, et al. Journal of the American Society of Nephrology , 2004, 15.7: 1889-1896.).

[0060] The above heart disease is a general term for diseases occurring in the heart, and the above heart disease may be, but is not limited to, failure, cardiac hypertrophy, cardiac fibrosis, angina pectoris, myocardial infarction, arteriosclerosis, heart valve disease, hypertension, hypotension, cor pulmonary heart, arrhythmia, ventricular fibrillation, pericarditis, or endocarditis.

[0061] N(ε)-carboxymethyllysine (CML) is a major advanced glycation product, and plasma CML is known to be elevated in aging, atherosclerosis, and / or diabetes and to be involved in the pathogenesis of heart disease; it has been reported that cardiac CML concentrations increase with age, diabetes, and / or coronary artery disease and show a positive correlation with plasma CML concentration (HU, Shengda, et al. The Tohoku journal of experimental medicine , 2013, 230.1: 25-32.).

[0062] The above-mentioned vascular disease refers to all diseases in which abnormalities in blood flow and blood volume occur due to damage or loss of vascular tissue caused by various injuries, including physical, oxidative, and inflammatory damage, to vascular endothelial cells. The above-mentioned vascular disease may include, but is not limited to, arteriosclerosis, hypertension, coronary artery disease, cerebrovascular disease, peripheral vascular disease, aortic disease, cerebral infarction, myocardial infarction, peripheral circulatory disorders, and ischemic encephalopathy. CML, a major advanced glycation end product, is associated with an increased risk of cardiovascular disease (KIZER, Jorge R., et al. Atherosclerosis , 2014, 235.1: 116-121.), CML levels reflect the presence of atherosclerosis in the coronary arteries (STANISLOVAITIENΛ, Daiva, et al. Medicina It has been reported as , 2016, 52.2: 99-103.).

[0063] The above aging is a concept that generally encompasses degenerative changes that occur as the structure and function of the body deteriorate with age. Changes resulting from aging are very diverse, including a decrease in the weight of each tissue and body weight due to a reduction in the number of parenchymal cells, changes in connective tissue, changes in body composition, a decrease in the elasticity of blood vessels or skin, a decline in the function of each organ, a decline in the ability to recover from disease including immune capacity, a decline in sensory organ function, and a decline in memory, learning ability, and comparison ability. The above aging may include one or more types of aging from the group consisting of muscle aging, skin aging, visual aging, auditory aging, digestive organ aging, immune aging, and urinary organ aging, but is not limited thereto.

[0064] The effects of advanced glycation end products on aging-related diseases such as Alzheimer's, Parkinson's, and cataracts have been studied, and it has been reported that there is a positive correlation between levels of advanced glycation end products (e.g., CML) and aging-related diseases such as age-related macular degeneration or cataracts (SADOWSKA-BARTOSZ, Izabela; BARTOSZ, Grzegorz. Mechanisms of Ageing and Development , 2016, 160: 1-18.; STANISLOVAITIENΛ, Daiva, et al. Medicina , 2016, 52.2: 99-103.; and GUL, Anjuman, et al. Journal of Diabetes and its Complications , 2009, 23.5: 343-348.).

[0065] The aforementioned uremia refers to various symptoms that occur when waste products that should be excreted through the kidneys in urine are not eliminated and accumulate in the body. Advanced glycation end products, which are products of the Maillard reaction in the body, have been reported to play an important role in various diseases, including normoglycemic uremia (HENNING, Christian, et al. Journal of Biological Chemistry , 2011, 286.52: 44350-44356.).

[0066] Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation in various joints, including the hands, wrists, feet, and ankles. The relationship between the accumulation of advanced glycation end products (AGEs) and rheumatoid arthritis has been studied. It has been reported that the overexpression of cytokines such as IL-1 and RAGE ligands in RA joints leads to increased expression of the AGE receptor (RAGE) in tissue macrophages, which amplifies inflammatory responses through RAGE-ligand interactions, and that high levels of RAGE expression in the vascular system promote the infiltration of monocytes and lymphocytes into synovial tissue (ST) (SUNAHORI, Katsue, et al. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology , 2006, 54.1: 97-104.).

[0067] The above-mentioned improvement of skin condition may include, but is not limited to, wrinkle improvement, prevention of skin aging, and prevention or improvement of the decrease in skin elasticity. The term "wrinkle improvement" in the present invention means maintaining or strengthening wrinkles and elasticity of the skin. The term "prevention of skin aging" in the present invention means preventing or delaying both chronological aging (intrinsic aging), which is natural aging caused by physiological changes in the body over time, and photoaging (photogenic aging), which occurs in areas exposed to sunlight.

[0068] Advanced glycation end products have been reported to increase during the skin aging process, and glycation reactions are further increased in photoaged skin (JEANMAIRE, C, et al. British Journal of Dermatology (GKOGKOLOU, Paraskevi; BΦHM, Markus.) Advanced Glycation Products, generated by the glycation reaction of proteins present in the skin, have been reported to cause reduced cell regeneration, decreased skin contractility, reduced elasticity, and reduced tissue permeability (GKOGKOLOU, Paraskevi; BΦHM, Markus. Dermato-endocrinology , 2012, 4.3: 259-270.).

[0069] The term "prevention" in this invention refers to any act of administering the pharmaceutical composition of this invention to an individual to suppress or delay diseases related to advanced glycation end products.

[0070] The term "improvement" in the present invention refers to any act of using the fern extract in the present invention to improve or benefit diseases related to advanced glycation end products, cholesterol levels, joint or bone health, or skin condition.

[0071] The food composition of the present invention may include the fern extract in various amounts, provided that it has the effect of inhibiting the formation of advanced glycation end products, inhibiting cross-linking of advanced glycation end products, or cleaving cross-linking of advanced glycation end products.

[0072] In the present invention, the fern extract may have activity of inhibiting the generation or accumulation of advanced glycation end products, or inhibiting, cleaving, or degrading the cross-linking of advanced glycation end products.

[0073] Advanced Glycation End Products (AGEs) are known to cause abnormal physicochemical changes in the body's structures and other protein-connected tissues through cross-linking with proteins such as collagen, thereby inducing diseases such as metabolic disorders, diabetic complications, Alzheimer's disease, kidney disease, heart disease, vascular disease, aging, uremia, cataracts, Parkinson's disease, or cancer. Therefore, the fern extract of the present invention, which possesses activity to inhibit, cleave, or degrade the cross-linking of AGEs with proteins, can be used for the prevention or treatment of these diseases.

[0074] The food composition of the present invention is very useful because, since it can be consumed on a daily basis, it is expected to have effects such as inhibiting the formation of advanced glycation end products, reducing advanced glycation end products in the body through inhibition of cross-linking, cleavage, or decomposition of advanced glycation end products, and preventing or improving diseases related to advanced glycation end products.

[0076] In another embodiment for achieving the above objective, the present invention provides a pharmaceutical composition for the prevention or treatment of advanced glycation end product-related diseases comprising a fern extract as an active ingredient.

[0077] The terms "fern," "extract," "active ingredient," "advanced glycation end product," "advanced glycation end product-related disease," and "prevention" of the present invention are as described above.

[0078] The term "treatment" in this invention refers to any act of administering the pharmaceutical composition of this invention to an individual to improve, alleviate, or benefit from diseases related to advanced glycation end products.

[0079] The pharmaceutical composition of the present invention may further comprise pharmaceutically acceptable carriers, excipients, or diluents according to conventional methods. Pharmaceutically acceptable carriers are known in the art according to the route of administration or formulation, and specifically, reference may be made to the pharmacopoeias of each country, including the Korean Pharmacopoeia. Carriers, excipients, and diluents that may be included in the composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition, carriers, excipients, and diluents that may be included in the composition of the present invention may be non-natural carriers, but are not limited thereto.

[0080] 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, as well as external preparations, suppositories, or sterile injectable solutions, according to conventional methods. Specifically, when formulating, it may be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, and surfactants that are commonly used. Solid formulations for oral administration include tablets, pills, powders, granules, and capsules, and such solid formulations may be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc., with the above compounds. In addition, lubricants such as magnesium stearate and talc may also be used in addition to simple excipients. Liquid formulations for oral administration include suspensions, oral liquids, emulsions, syrups, etc. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as humectants, sweeteners, flavorings, and preservatives, may be included. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used. As bases for suppositories, Witepsol, Macrogol, Tween 61, cocoa dough, laurin dough, glycerogelatin, etc., may be used. Specific formulations of pharmaceutical compositions are known in the art, and reference may be made to literature such as [Remington's Pharmaceutical Sciences (19th ed., 1995)]. The said literature is considered to be part of this specification.

[0081] The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. The pharmaceutically effective amount refers to an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment and that does not cause adverse effects. The effective dose level may be determined based on factors including the patient's health status, type and severity of the disease, drug activity, sensitivity to the drug, method of administration, time of administration, route of administration and elimination rate, duration of treatment, drugs used in combination or concurrently, and other factors well known in the medical field. The dosage and frequency of administration do not limit the scope of the present invention in any way.

[0082] The pharmaceutical composition of the present invention may be administered to mammals such as rats, dogs, cats, cattle, horses, pigs, and humans via various routes, and may be preferred in humans. Any mode of administration may be anticipated and may be administered, for example, orally, intravenously, intramuscularly, or by subcutaneous injection, but is not limited thereto.

[0083] In another embodiment for achieving the above objective, the present invention provides a quasi-drug composition for the improvement, prevention, or treatment of diseases related to advanced glycation end products, comprising a fern extract as an active ingredient.

[0084] The term "quasi-drug" as used in the present invention refers to articles used for the purpose of diagnosing, treating, alleviating, managing, or preventing diseases in humans or animals, excluding instruments, machines, or devices, and articles used for the purpose of having a pharmacological effect on the structure and function of humans or animals, excluding instruments, machines, or devices. One embodiment may include, but is not limited to, an oral formulation. The formulation method, dosage, method of use, and components of the quasi-drug may be appropriately selected from the ordinary technology known in the technical field.

[0085] The quasi-drug composition of the present invention may further include, in addition to the above components, a pharmaceutically acceptable carrier, excipient, or diluent as needed. The pharmaceutically acceptable carrier, excipient, or diluent is not limited as long as it does not impair the effects of the present invention, and may include, for example, fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, fragrances, preservatives, etc.

[0087] In another embodiment for achieving the above objective, the present invention provides a feed composition for the prevention or improvement of diseases related to advanced glycation end products, comprising a fern extract as an active ingredient.

[0088] In the present invention, the feed composition may be formulated in the form of a conventional feed and may include known feed ingredients. Additionally, it may be used as a feed additive added to the feed in the form of an additive. The feed additive of the present invention corresponds to a supplementary feed under the Feed Management Act and may additionally include mineral preparations such as sodium bicarbonate (baking soda), bentonite, magnesium oxide, and complex minerals; mineral preparations that are trace minerals such as zinc, copper, cobalt, and selenium; vitamin preparations such as carotene, vitamin E, vitamins A and D, nicotinic acid, and vitamin B complex; protected amino acid preparations such as methionine and lysic acid; protected fatty acid preparations such as calcium salts of fatty acids; probiotics (lactic acid bacteria preparations); probiotics such as yeast cultures and mold fermentation products; and yeast preparations.

[0089] The feed or feed additive of the present invention can be applied to a number of animal diets, including mammals, poultry, and fish. Effects of the invention

[0091] The bracken extract according to the present invention exhibits excellent activity in inhibiting the formation and accumulation of advanced glycation end products (AGEs), and also shows effects of inhibiting, cleaving, and degrading the cross-linking of AGEs and collagen. Therefore, a composition containing the bracken extract can be used not only for inhibiting the formation of AGEs or for inhibiting, cleaving, or degrading the cross-linking of AGEs, but can also be usefully employed in the manufacture of foods and pharmaceuticals for the prevention, improvement, or treatment of diseases caused by AGEs. Brief explanation of the drawing

[0093] Figure 1 is a graph showing the results of analyzing the degree of cell viability according to the concentration of the fern extract treatment of the present invention. Figure 2 is a graph showing the results of analyzing the degree of advanced glycation end product formation according to the treatment concentration of the bracken extract of the present invention. Figure 3 is a graph showing the results of analyzing the degree of cross-linking between the advanced glycation end product and collagen according to the fern extract treatment of the present invention. Specific details for implementing the invention

[0094] The structure and effects of the present invention will be explained in more detail below through examples. These examples are intended solely to illustrate the present invention, and the scope of the present invention is not limited by them.

[0096] Example 1: Preparation of fern extract

[0097] The bracken used in this experiment was purchased from the market.

[0098] Bracken was washed and dried, then ground to a uniform size. 70% fermented alcohol (ethanol, 100 g / L) was added to the ground bracken, and extraction was performed twice for 3 hours each at 50°C. The supernatant was filtered, concentrated under reduced pressure, and freeze-dried, then stored at -20°C for use.

[0100] Experimental Example 1: Confirmation of Cell Viability Activity of Fern Extract

[0101] To confirm the cell viability activity of the fern extract, an MTT assay was performed by treating with MGO (Methylglyoxal).

[0102] The NRK-52E cells used in this experiment were obtained from ATCC (American Type Culture Collection) and cultured in DMEM medium supplemented with 10% heat-inactivated FBS (10 units / mL penicillin, 10 μg / mL streptomycin) at 37℃ under 5% CO2 conditions.

[0103] NRK-52E cells were placed in a 96-well plate at a density of 3×10⁶ 4 Cells were seeded into cells / well and cultured in a cell culture incubator for 24 hours. After removing all supernatant, 700 μM MGO and fern extracts (50 μg / mL and 200 μg / mL), respectively, were added and cultured for an additional 24 hours. Subsequently, 0.1 mg / mL of MTT reagent was added, and the cells were incubated for 3 hours at 37°C under 5% CO2 conditions. The cells were then dissolved in an equal volume of DMSO, and the absorbance was measured at 595 nm. Cell viability (%) was expressed using the following formula.

[0104] - Cell viability (%) = (Absorbance of sample treatment group / Absorbance of control group) x 100

[0105] As a result, as shown in Figure 1, the control group treated with MGO showed a cell viability of 73%, whereas the cell viability of the fern extract treated with 200 μg / mL of the present invention increased to 105%, confirming the cell viability activity of the fern extract.

[0107] Experimental Example 2: Confirmation of the inhibitory effect of bracken extract on the formation of advanced glycation end products

[0108] To confirm the inhibitory effect of fern extract on the formation of advanced glycation end products, BSA (Bovine serum albumin) was used as the protein source, and an efficacy evaluation was conducted using glucose and fructose as the glycosides.

[0109] 0.02% sodium azide was added to 50 mM phosphate buffer to prevent contamination of the reactants due to microbial growth, and 10 mg / ml of BSA and 0.2 M glucose and fructose were added to the phosphate buffer to prepare the reactants. These reactants were treated with fern extract (50 μg / mL and 200 μg / mL) and aminoguanidine (AG; positive control; 1 mM), a standard inhibitor of advanced glycation end products, respectively.

[0110] After reacting each reactant at 37°C for 14 days, the inhibitory effect of the fern extract on the formation of advanced glycation end products was confirmed through fluorescence analysis (Molecular Devices, Sunnyvale, CA, USA) measurements at wavelengths of excitation 350 nm and emission 450 nm. The formula for calculating the measurements is as follows.

[0111] AGEs formation (%) = (Fluorescence value of reactant with extract / Fluorescence value of reactant without extract) × 100

[0112] As a result, as shown in Figure 2, in the evaluation test of advanced glycation end products generated by the mixed reaction of protein and sugar, compared to the AGEs group reacted with only protein and sugar, the fern extract treatment group of the present invention showed a decrease in the production of advanced glycation end products at all concentration groups, confirming the efficacy of the fern extract in inhibiting the production of advanced glycation end products.

[0114] Experimental Example 3: Confirmation of the inhibitory effect of bracken extract on Advanced Glycation End Product-collagen cross-linking

[0115] To evaluate the inhibitory effect of advanced glycation end product cross-linking, AGE-BSA was dispensed into collagen-coated 96-well microplates along with the extract and reacted for a certain period of time. Specifically, Kit-NH₂ (Dojindo Molecular Technologies, Inc., Tokyo, Japan) conjugated with Horseradish peroxidase (HRP) was used as the AGE-BSA. The sample was dispensed into collagen plates at a concentration of 10 μg / mL, treated with fern extract (at concentrations of 50 μg / mL and 200 μg / mL) and the positive control AG (1 mM), respectively, and incubated at 37°C for 18 hours. After the cross-linking reaction was complete, the reaction product was removed and washed three times with 0.05% PBST (prepared to contain 0.05% Tween 20 in PBS). Subsequently, color development was performed using tetramethylbenzidine (TMB) as a substrate, and the absorbance was measured at 450 nm. The cross-linking ratio of advanced glycation end products and collagen was calculated as follows.

[0116] AGE-BSA and collagen cross-linking ratio (%) = (Absorbance of sample-added group / Absorbance of non-sample-added group) × 100

[0117] As a result, as shown in Figure 3, the group treated with AG (1 mM), known as an inhibitor of advanced glycation end product crosslinking, showed a crosslinking inhibitory efficacy of 77%, whereas the group treated with 200 μg / mL of the bracken extract of the present invention showed a crosslinking inhibitory efficacy of 100%. Since the bracken extract showed a superior inhibitory effect on advanced glycation end product crosslinking compared to the AG treatment group at a concentration of 200 μg / mL, it was confirmed that the bracken extract of the present invention has excellent inhibitory efficacy against irreversible crosslinking between advanced glycation end products and collagen.

[0119] Experimental Example 4: Confirmation of the efficacy of bracken extract in cleaving Advanced Glycation End Product-collagen crosslinks

[0120] To confirm the cross-cleavage efficacy of the fern extract on advanced glycation end products, HRP-attached AGE-BSA was dispensed into collagen-coated 96-well microplates and reacted, after which the extract was added and reacted for a certain period. Specifically, AGE-BSA was dispensed into collagen plates and reacted at 37°C for 4 hours. After the cross-linking reaction between collagen and AGE-BSA, the reaction mixture was removed and washed three times with 0.05% PBST. The prepared fern extracts (50 μg / mL and 200 μg / mL) and the positive control, 1 mg / mL of ALT-711 (Algebrium), were each added and incubated for 18 hours. After the reaction, the reaction mixture was removed and washed three times with 0.05% PBST. Color development was then performed using TMB as a substrate, and the absorbance was measured at 450 nm and calculated as follows.

[0121] AGE-BSA and collagen cross-linking ratio (%) = (Absorbance of sample-added group / Absorbance of non-sample-added group) × 100

[0122] As a result, it was confirmed that the fern extract of the present invention has a cleaving effect on irreversible cross-linking between advanced glycation end products and collagen, as the group treated with 200 μg / mL of the fern extract of the present invention showed 11% cross-linking cleaving efficacy.

Claims

Claim 1 A food composition for inhibiting, cleaving, or degrading cross-linking of advanced glycation end products comprising a bracken extract as an active ingredient, wherein the bracken extract is obtained by adding 70% ethanol to bracken and extracting it twice at a temperature of 50°C for 3 hours each time. Claim 2 delete Claim 3 A food composition for the prevention or improvement of diseases related to advanced glycation end products comprising a bracken extract as an active ingredient, wherein the bracken extract is obtained by adding 70% ethanol to bracken and extracting it twice at a temperature of 50°C for 3 hours each, wherein the diseases related to advanced glycation end products are metabolic diseases or diabetic complications, wherein the diseases related to advanced glycation end products are caused by the accumulation of advanced glycation end products, wherein the metabolic diseases are selected from the group consisting of obesity, non-alcoholic fatty liver disease, and non-alcoholic fatty liver hepatitis, and wherein the diabetic complications are selected from the group consisting of diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic foot ulcer, and diabetic osteoporosis. Claim 4 delete Claim 5 delete Claim 6 delete Claim 7 delete Claim 8 delete Claim 9 A food composition according to paragraph 3, wherein the fern extract has crosslinking inhibitory, cleavage, or degradation activity of advanced glycation end products. Claim 10 A health functional food for the prevention or improvement of advanced glycation product-related diseases comprising a food composition according to any one of claims 1, 3 and 9, wherein the advanced glycation product-related disease is a metabolic disease or a diabetic complication, the advanced glycation product-related disease is caused by the accumulation of advanced glycation products, the metabolic disease is selected from the group consisting of obesity, non-alcoholic fatty liver and non-alcoholic fatty liver hepatitis, and the diabetic complication is selected from the group consisting of diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic foot ulcer and diabetic osteoporosis. Claim 11 A pharmaceutical composition for the prevention or treatment of diseases related to advanced glycation end products comprising a fern extract as an active ingredient, wherein the fern extract is obtained by adding 70% ethanol to a fern and extracting it twice at a temperature of 50°C for 3 hours each time, wherein the diseases related to advanced glycation end products are metabolic diseases or diabetic complications, wherein the diseases related to advanced glycation end products are caused by the accumulation of advanced glycation end products, wherein the metabolic diseases are selected from the group consisting of obesity, non-alcoholic fatty liver disease, and non-alcoholic fatty liver hepatitis, and wherein the diabetic complications are selected from the group consisting of diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic foot ulcer, and diabetic osteoporosis. Claim 12 delete Claim 13 delete Claim 14 delete Claim 15 delete Claim 16 A pharmaceutical composition according to claim 11, wherein the fern extract has crosslinking inhibitory, cleavage, or degradation activity of advanced glycation end products. Claim 17 A quasi-drug composition for the prevention, improvement, prevention, or treatment of diseases related to advanced glycation end products, comprising a bracken extract as an active ingredient, wherein the bracken extract is obtained by adding 70% ethanol to bracken and extracting it twice at a temperature of 50°C for 3 hours each; wherein the diseases related to advanced glycation end products are metabolic diseases or diabetic complications; wherein the diseases related to advanced glycation end products are caused by the accumulation of advanced glycation end products; wherein the metabolic diseases are selected from the group consisting of obesity, non-alcoholic fatty liver disease, and non-alcoholic fatty liver hepatitis; and wherein the diabetic complications are selected from the group consisting of diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic foot ulcer, and diabetic osteoporosis. Claim 18 A feed composition for the prevention or improvement of diseases related to advanced glycation end products, comprising a bracken extract as an active ingredient, wherein the bracken extract is obtained by adding 70% ethanol to bracken and extracting it twice at a temperature of 50°C for 3 hours each time, wherein the diseases related to advanced glycation end products are metabolic diseases or diabetic complications, wherein the diseases related to advanced glycation end products are caused by the accumulation of advanced glycation end products, wherein the metabolic diseases are selected from the group consisting of obesity, non-alcoholic fatty liver disease, and non-alcoholic fatty liver hepatitis, and wherein the diabetic complications are selected from the group consisting of diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic foot ulcer, and diabetic osteoporosis.

Images