Composition for the prevention or treatment of fatty liver

Abstract

The present invention relates to a composition for the prevention or treatment of fatty liver and a health functional food comprising same, and more particularly to a composition for the prevention or treatment of fatty liver, comprising plant extracts, dibenzo-p-dioxine derivatives and polyphenolic compounds, and a health functional food comprising same.

Description

COMPOSITION FOR THE PREVENTION OR TREATMENT OF FATTY LIVER

[0001] The present invention relates to a composition for the prevention or treatment of fatty liver and health functional foods comprising same, and more particularly to a composition for the prevention or treatment of fatty liver comprising plant extracts, dibenzo-p-dioxine derivatives and polyphenolic compounds, and health functional foods comprising same.

[0002]

[0003] Alcoholic fatty liver disease is caused by chronic alcohol consumption and can be accompanied by cirrhosis, fibrosis, hepatitis, and liver cancer. In particular, alcoholic fatty liver disease (AFLD) is responsible for at least 3 million deaths in many countries. The three-month mortality rate for patients with severe alcoholic steatohepatitis is as high as 40-50%. With few treatments available for AFLD, there is a need to discover useful new therapies.

[0004] Any fatty liver disease that encompasses a fatty liver similar to alcoholic liver disorders that occur in non-drinkers is referred to as non-alcoholic fatty liver disease (NAFLD). In patients with NAFLD, fatty acid synthesis in the liver is always activated, and activation of fatty acid synthesis is an important factor in the formation of fatty liver that results from metabolic syndrome.

[0005] Non-alcoholic fatty liver disease is generally divided into simple fatty liver, which is considered to have a good prognosis, and non-alcoholic steatohepatitis (NASH), which is considered to have a poor prognosis due to persistent inflammation or fibrosis in the simple fatty liver, and NASH is a severe form of NAFLD. Statistics show that approximately 30% of the fatty liver population has NASH, and 10-29% of patients with NASH progress to cirrhosis, or further to liver cancer or death (Younossi ZM. Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol. 2019;70(3):531-544).

[0006] However, despite the fact that NASH is a severe disease that progresses to cirrhosis and liver cancer, there are currently no drugs with significant clinical improvement in NASH.

[0007] Meanwhile, Korean Patent Publication No. 2006-0020923 discloses a functional food composition effective in relieving hangovers and improving liver function, comprising 6 to 18% by dry weight of Polygonatum var., 10 to 40% by dry weight ofAstragalus membranaceus Bge., 5 to 15% by dry weight of Artemisiae Scopariae Herba, 10 to 30% by dry weight of White Hoelen, 5 to 25% by dry weight ofAtractylodes macrocephala koidz, 4 to 12% by dry weight of Rehmanniae Radix, 2 to 10% by dry weight ofMentha arvensis, 2 to 10% by dry weight ofCurcuma longa, and 2 to 10% by dry weight of Puerariae Radix, based on the total dry weight of the composition.

[0008] In addition, Korean Patent No. 0988510 discloses a composition for the prevention or treatment of type 2 diabetes that have the property of inhibiting the activity of Nuclear Factor Kappa B (NFkB), including dibenzo-p-dioxine derivatives.

[0009] Under this technical background, the inventors of the present invention recognized the urgent need for research into the prevention or treatment of alcoholic or non-alcoholic fatty liver, and have completed the present invention.

[0010]

[0011] An object of the present invention is to provide a composition for the prevention or treatment of fatty liver, a method of preventing or treating fatty liver, and use in the preparation for the prevention or treatment of fatty liver.

[0012] It is also an object of the present invention to provide a health functional food comprising a composition for the prevention or treatment of fatty liver.

[0013]

[0014] To accomplish the above objectives, the present invention provides a composition for the prevention or treatment of fatty liver comprising:

[0015] (1) dibenzo-p-dioxine derivatives; and

[0016] (2) polyphenolic compounds.

[0017] The present invention provides a method of preventing or treating fatty liver, comprising the step of administering to an individual a composition comprising:

[0018] (1) dibenzo-p-dioxine derivatives; and

[0019] (2) polyphenolic compounds.

[0020]

[0021] The present invention provides use in the preparation of a composition for the prevention or treatment of fatty liver, comprising:

[0022] (1) dibenzo-p-dioxine derivatives; and

[0023] (2) polyphenolic compounds.

[0024] The present invention may further comprise 5 to 12% by dry weight of Polygonatum var., 10 to 20% by dry weight of Astragalus membranaceus Bge., 5 to 15% by dry weight of Artemisiae Scopariae Herba, 2 to 7% by dry weight of Puerariae Radix, 10 to 45% by dry weight of Codonopsis polisula NANNF, 10 to 20% by dry weight of White Hoelen, 5 to 20% by dry weight of Atractylodes macrocephala koidz, 5 to 15% by dry weight of Rehmanniae Radix, 2 to 10% by dry weight of Curcuma longa, and 2 to 10% by dry weight of Mentha arvensis

[0025] The present invention relates to a health functional food for the prevention or amelioration of fatty liver, comprising:

[0026] (1) dibenzo-p-dioxine derivatives; and

[0027] (2) polyphenolic compounds.

[0028] The present invention may further comprise 5 to 12% by dry weight of Polygonatum var., 10 to 20% by dry weight of Astragalus membranaceus Bge., 5 to 15% by dry weight of Artemisiae Scopariae Herba, 2 to 7% by dry weight of Puerariae Radix, 10 to 45% by dry weight of Codonopsis polisula NANNF, 10 to 20% by dry weight of White Hoelen, 5 to 20% by dry weight of Atractylodes macrocephala koidz, 5 to 15% by dry weight of Rehmanniae Radix, 2 to 10% by dry weight of Curcuma longa, and 2 to 10% by dry weight of Mentha arvensis

[0029]

[0030] A composition comprising dibenzo-p-dioxin derivatives and polyphenolic compounds according to the present invention can exhibit excellent preventive or therapeutic effects on fatty liver, for example, on alcoholic or non-alcoholic fatty liver disease.

[0031]

[0032] FIG. 1a shows the results of weight change (g) in mice administered with the composition according to Preparation Example 1.

[0033] FIG. 1b is a result showing % body weight change in mice administered with the composition according to Preparation Example 1.

[0034] FIG. 2 shows results showing little difference in adipose tissue when fed with the composition according to Preparation Example 1 after 30 days.

[0035] (A) In the control group experiment, fat mice after 30 days had abundant adipose tissue in the abdomen and around internal organs. Adipocytes are densely packed and separated by thin strips of connective tissue that are loose and irregular. X80 H&E

[0036] (B) At higher magnification, individual adipocytes appeared empty. The fat was dissolved by the chemical solution used in routine histological preparation. Numerous blood vessels were visible in the adipose tissue (arrows). X120 H&E

[0037] After 30 days of feeding with the composition according to Preparation Example 1, it was shown that in the adipose tissue, the adipocytes (AC) were slightly full and the cytoplasmic membrane was looser and less tight (FIG. 2A). More dense and many fibroblasts were visible in the adipocytes (AC) as well (arrows). In addition, there were fewer small blood vessels in the adipose tissue. X120 H&E

[0038] FIG. 3 shows the results of the muscle study. The effect of feeding the composition according to Preparation Example 1 on the leg skeletal muscle of fat mice was studied. Skeletal muscle is attached to multiple bones and moves the bones accordingly. Skeletal muscle is long, multinucleated fibres. The longitudinal and parallel arrangement of fibres is held together by connective tissue. Skeletal muscle is innervated by large motor nerves. All skeletal muscle fibres are innervated.

[0039] (A) Mice fed water and normal mouse chow after 30 days. Fat mice have abundant adipose tissue (FAT) between muscle bundles. Many adipocytes (ad) are infiltrated between muscle fibres (MB). In fat mouse muscle tissue, skeletal muscle fibre groups were separated by abundant adipocytes. Neurons (NU) are visible in the cross-section. X80 H&E

[0040] (B) In the group fed the composition of Preparation Example 1, significantly fewer adipocytes (ad) were found between muscle fibre interfaces (MB) compared to the control group. Adipocytes of various sizes (arrows) were adherent to the muscle fibres, indicating lipid resorption. The connective tissue contained collagen (arrowheads) in a fairly normal shape.

[0041] FIG. 4 shows the results of a study of the liver. The liver is an endocrine and exocrine organ. Hepatocytes secrete bile in bile ducts. The bile salts present in bile are necessary to emulsify fats that enter the small intestine from the stomach. The bile then helps pancreatic lipase to digest fat. The liver also stores glycogen and fat. The histological structure and cellular composition of the mouse liver is the same as in humans.

[0042] (A) In a 30-day study of the control group of fat mice, fat mice produced an imbalanced oxidation mechanism. The finished oxidised substances were converted into fat by fatty acids. A fatty liver appeared (arrows). The fatty changes in the liver are reversible, even though they are very extensive. X120 H&E

[0043] (B) A fatty mouse liver treated with the composition of Preparation Example 1 still appears fatty (see arrows). Very little glycogen was observed in the liver. X120 PAS

[0044] FIG. 5 shows the results for the pancreas. Observation of pancreatic tissue during the 30-day feeding experiment showed that low cuboidal epithelial cells were lined in the small intra-lobular duct, and adipose tissues were distributed in the pancreatic vessels. Adipose tissue was infiltrated between pancreatic lobules.

[0045] (A) Adipocytes were not involved in the pancreatic sublingual glands or acini. Adipose tissue easily causes acute pancreatitis as lipase causes adipocyte necrosis.

[0046] (B) The group fed the composition of Preparation Example 1 did not accumulate adipose tissue at the selected sites. The endocrine portion of the islets of Langerhans (IS) was visible. Few fat droplets were observed in the arches (arrows).

[0047] FIG. 6 shows the results of the adipose tissue study. (A) At 60 days of feeding, the adipose tissue of the animals showed differences between the two groups of fat mice.

[0048] (B) Fat mice not treated with the composition of Preparation Example 1 showed a higher concentration of fat in the abdomen. The adipose tissue contains more normal adipocytes with many blood vessels (arrows). X120 H&E

[0049] (C) Adipose tissue of mice fed the composition of Preparation Example 1 is filled with lost fat droplets (arrows). Fibroblasts are clearly more abundant (open arrows). This indicates that the adipocytes are being resorbed, presumably by feeding the composition of Preparation Example 1, and more fibroblasts and loose connective tissue are appearing.

[0050] FIG. 7 shows the results for muscle. At day 60 of feeding, control animals showed the development of adipocytes in the intramuscular fibres (MB).

[0051] (A) Adipocytes (ad) are located around blood vessels (BV).

[0052] (B) A trichrome-stained section shows that adipose tissue is associated with blood vessel (BV). Collagen (blue, arrow) is highly prominent in the fatty mouse muscle.

[0053] (C) Neurons (NU) were located in adipose tissue in muscle fibre (MB). Adipocytes (ad) were associated with collagen in connective tissue.

[0054] FIG. 8 shows the results for muscle. Micrographs show the effect of feeding the composition of Preparation Example 1 on adipose suppression of adipocytes in muscle tissue observed over a period of 60 days.

[0055] (A) There are significantly fewer adipocytes (FAT) in adipose tissue compared to control animals. The inhibition of adipocyte synthesis and development by feeding the composition of Preparation Example 1 is probably due to increased lipid uptake and oxidation, which reduces the number of adipocytes in the intercellular muscle fibres (MB).

[0056] (B) Masson's trichrome stained muscle of a mouse fed the composition of Preparation Example 1 shown in FIG. 8A. There is little collagen in and around the adipose tissue.

[0057] (C) Skeletal muscle from another animal showing stained collagen in the surrounding adipocytes (arrow heads) is shown. The adipocytes (AD) vary in size and the thick deposition of collagen indicates that the adipocytes are being taken up and reduced by the connective tissue.

[0058] FIG. 9 shows the results for the liver. (A) After 60 days of feeding, the liver of a control fat mouse shows that the liver cells contain more fat vacuoles (arrows). The fatty liver is more evident compared to at 30 days.

[0059] (B) In the group fed the composition of Preparation Example 1, the liver cells show very scaly fat droplets and glycogen deposition is visible in some cells (arrows). PAS staining was used to illustrate the glycogen in the hepatocytes.

[0060] FIG. 10 shows the results for the pancreas. Fat mice fed the composition of Preparation Example 1 showed significantly reduced fat accumulation in the pancreas.

[0061] (A) Adipocytes (FAT) accumulated in endocrine islets (IS) and exocrine acini. Fat accumulation in the pancreas is uncommon in normal C57 / BL mice, but occurs in fat mice.

[0062] (B) At high magnification, the acini of a control mouse pancreas show fat droplets (arrows) in the cytoplasm.

[0063] (C) Mice fed the composition of Preparation Example 1 for 60 days show a reduction in fat droplets in the acini and the absence of adipocytes associated with the islets of Langerhans (IS).

[0064] FIG. 11 shows results for adipose tissue. Feeding the composition of Preparation Example 1 for 120 days resulted in a change in the number of blood vessels (BV, arrows) in the adipose tissue (AD).

[0065] (A) In the control group, adipose tissue was shown to have more blood vessels and capillaries (arrows).

[0066] (B) Adipose tissue (AD) in the group fed with the composition of Preparation Example 1 was shown to have a lower number of blood vessels (BV) and capillaries (arrows).

[0067] FIG. 12 shows the results for skeletal muscle. After 120 days of feeding, the difference between the group fed with the composition of Preparation Example 1 and the control group in skeletal mouse adipocytes was significant.

[0068] (A) Adipocytes (AD) are located in the intermuscular fibres and the adipocytes are mature and have normal characteristics.

[0069] (B) After feeding the composition of Preparation Example 1 for 120 days, the muscle fibres show significantly fewer adipocytes (ad). The adipocytes are closely associated with the surface of the blood vessels (arrows).

[0070] (C) A mouse skeleton (BV) showing little or no adipocytes (arrows) in and around blood vessels is shown.

[0071] FIG. 13 shows the results for the liver. The smallest unit is the acinus. The portal central vein (CV) contains partially oxygenated blood. Fat storage in the liver is due to changes in the metabolic activity of hepatocytes. The accumulation of fat in the liver in fat mice is due to the fact that many liver enzymes enable the metabolism of fats and carbohydrates.

[0072] (A) Hepatocytes from the control group in a 120-day feeding experiment show a marked accumulation of fat droplets in the cytoplasm (arrows).

[0073] (B) In the group fed the composition of Preparation Example 1, the central venous (CV) region of the liver showed little or no hepatocytes with fat accumulation in the cytoplasm. Few foci containing haematopoietic cells (arrowheads) were observed.

[0074] FIG. 14 shows results for the pancreas. Treatment with the composition of Preparation Example 1 reduces the number of adipocytes (ad). Mice fed the composition of Preparation Example 1 have reduced adipocytes in organs involved in fat metabolism.

[0075] (A) Many large adipocytes are seen in the acini region of the pancreas (arrows).

[0076] (B) When mice were fed the composition of Preparation Example 1, the pancreas had a normal appearance and was determined to have normal endocrine and exocrine systems. However, fat droplets in the acini are still occasionally observed (arrows).

[0077] FIG. 15 shows the results for the muscles. At the end of the 120-day (4-month) experiment, four mice from the SBD X2-fed group and two fat mice from the control group were preserved for further observation. All mice were housed under the same water and food conditions. After one month, the SBD X2 group was almost as inactive as the control group. In general, they were all very inactive and often grouped together.

[0078] (A) Control fat mice have adipocytes in their muscles, a typical characteristic of fat mice.

[0079] (B) In the intercellular muscle fibre space, a thickening of collagen in the connective tissue was shown, but only a few adipocytes were identified.

[0080] FIG. 16 is a schematic of the study. Animals were fed a control diet or FFC for 6 weeks, and then randomly assigned at baseline to receive the composition or no additional administration (NAFLD prevention model, groups 1-4). In addition, in three additional groups (NAFLD treatment model, groups 5-7), one FFC group was added with the composition at week 1 for a total of 9 additional weeks.

[0081] FIG. 17 shows the results of liver biochemistry studies in the NAFLD prevention model.

[0082] FIG. 18 shows the area of liver fat percentage in the NAFLD prevention model (image x 10x magnification, statistical ANOVA).

[0083] FIG. 19 shows serum high-density lipoprotein (HDL) levels during NAFLD.

[0084] FIG. 20 shows the area of liver fat percentage in the NAFLD treatment model (image x 10 magnification, statistical ANOVA post-hoc Tukey test).

[0085] FIG. 21 shows serum high-density lipoprotein (HDL) in the NAFLD treatment model (statistical ANOVA post-hoc Tukey test).

[0086]

[0087] [Detailed Description of the Invention]

[0088] Unless otherwise defined, all technical and scientific terms used herein shall have the same meaning as commonly understood by those skilled in the art. In general, the nomenclature used herein is well known and in common use in the art.

[0089] The inventor of the present invention has disclosed research results on the effects of plant extracts in relieving hangovers and improving liver function, and research results on the effects of dibenzo-p-dioxine derivatives having a property of inhibiting the activity of NFkB in improving diabetes. However, the effect of plant extract, dibenzo-p-dioxine derivatives and polyphenolic compounds provided in the present invention in improving fatty acid liver has not been disclosed yet.

[0090] Based on this, the present invention relates, in one aspect, to a composition for the prevention or treatment of fatty liver comprising:

[0091] (1) dibenzo-p-dioxine derivatives; and

[0092] (2) polyphenolic compounds.

[0093] In another aspect, the present invention relates to a method of preventing or treating fatty liver, comprising the step of administering to an individual a composition comprising:

[0094] (1) dibenzo-p-dioxine derivatives; and

[0095] (2) polyphenolic compounds.

[0096] In another aspect, the present invention relates to use in the preparation of compositions for the prevention or treatment of fatty liver, comprising:

[0097] (1) dibenzo-p-dioxine derivatives; and

[0098] (2) polyphenolic compounds.

[0099] In another aspect, the present invention relates to a health functional food for the prevention or amelioration of fatty liver, comprising:

[0100] (1) dibenzo-p-dioxine derivatives; and

[0101] (2) polyphenolic compounds.

[0102] In some cases, the present invention may comprise 5 to 12% by dry weight of Polygonatum var., 10 to 20% by dry weight of Astragalus membranaceus Bge., 5 to 15% by dry weight of Artemisiae Scopariae Herba, 2 to 7% by dry weight of Puerariae Radix, 10 to 45% by dry weight of Codonopsis polisula NANNF, 10 to 20% by dry weight of White Hoelen, 5 to 20% by dry weight of Atractylodes macrocephala koidz, 5 to 15% by dry weight of Rehmanniae Radix, 2 to 10% by dry weight of Curcuma longa, and 2 to 10% by dry weight of Mentha arvensis.

[0103] The present invention comprises 5 to 12% by dry weight of Polygonatum var., 10 to 20% by dry weight of Astragalus membranaceus Bge., 5 to 15% by dry weight of Artemisiae Scopariae Herba, 2 to 7% by dry weight of Puerariae Radix, 10 to 45% by dry weight of Codonopsis polisula NANNF, 10 to 20% by dry weight of White Hoelen, 5 to 20% by dry weight of Atractylodes macrocephala koidz, 5 to 15% by dry weight of Rehmanniae Radix, 2 to 10% by dry weight of Curcuma longa, and 2 to 10% by dry weight of Mentha arvensis.

[0104] Polygonatum var. (pluriflorum OHWI) is a perennial herb of the lily family, and according to the Dongui Bogam, "Polygonatum var. is a herbal medicine that has received the essence of the sun, so if you eat it, you will feel lighter, energized, and live a long life, as it is a medicine that nourishes the weak and frail body, strengthens muscles and bones, clears the mind, nourishes the liver and kidneys, enhances vitality, and soothes the mind." Polygonatum var. contains a large amount of mucilage, starch, sugar, cardiac glycosides (cornvalamarin, cornvalarin), alkaloids, vitamin A, and azetidine-2-carboxylic acid, and is used as a nourishing laxative and a nourishing tonic. It has a sweet flavor and is especially good for nourishing the five intestines, protecting the liver and improving liver function. It also contains cardiac glycosides, so it is effective for chest tightness, thirst, and lack of saliva in the mouth. The content of Polygonatum var. may be 5 to 12% by weight, more particularly 8 to 12% by weight, and more particularly 10 to 12% by weight based on dry weight.

[0105] Astragalus membranaceus Bge. is a perennial plant of the legume family and its roots are used medicinally, which contain components such as fomononetin, betain, cholin, isoliquiritigenin, amino acids, saponins, and isoflavones. Astragalus membranaceus Bge. has been reported to exhibit pharmacological effects such as protecting the liver, promoting immunity, strengthening the heart, and diuretic properties (Chinese Herbal Dictionary, p. 121, Shanghai Science and Technology Publishing House, Tokyo, 1985). Korean patent application Nos. 1994-040125 and 1999-010284 disclose that Astragalus membranaceus Bge. promotes immune function, is effective against hepatitis caused by carbon tetrachloride, and lowers blood pressure due to diuretic action. In particular, isoflavones extracted from Astragalus membranaceus Bge. have been shown to protect the liver. According to "Dongui Bogam," "Astragalus membranaceus Bge. is good for skin beauty, blood pressure regulation, prevention of pus formation, and blood and skin nourishment, and is especially effective in restoring vitality in individuals with weak constitutions and those who sweat excessively." The content of Astragalus membranaceus Bge.may be 10 to 20% by weight by dry weight, more particularly 12 to 18% by weight, and more particularly 15 to 18% by weight.

[0106] Artemisiae Scopariae Herba (Herba artmesiae capillaries) is rich in nutritional components that activate the liver function caused by alcohol, tobacco, excessive work, stress, frequent drinking, and various drugs, and many active nutrients, vitamins, and minerals, and is known to help improve liver function, cleanse the liver by discharging toxic wastes from the body, help the liver detoxify, smooth fat metabolism, and improve fatigue and physical strength. The content of Artemisiae Scopariae Herba may be 5 to 15% by weight, more particularly 6 to 13% by weight, and more particularly 7 to 12% by weight based on dry weight.

[0107] Puerariae Radix is effective in relaxing the pores of the skin and causing sweating, relieving fever, headache, and stiffness of the nape of the neck, quenching thirst, and relieving tightness and discomfort in the chest caused by fevers, which cause inability to keep the limbs still, and wasting-thirst. It is also known to be used for people with weak digestive systems who have diarrhea for a long time and are exhausted. The decoction of Puerariae Radix has a certain effect on strengthening blood pressure, the alcohol extract has an antipyretic effect, and the powder is known to have a vasodilating effect on the skin. The content of the Puerariae Radix may be 2 to 7% by weight by dry weight, more particularly 3 to 6% by weight, and even more particularly 4 to 5% by weight.

[0108] Codonopsis pilosula NANNF is a perennial plant of the bellflower family, containing alkaloids, B vitamins, saponins, sucrose, glucose, inulin, starch, and mucilage, and is used for expectorant effects, tonic effects, treatment of chronic wasting diseases, chronic respiratory diseases, and anemia, stomachic effects, and treatment of chronic gastritis. It calms the mind and is beneficial for chlorosis (anemia characterized by a lack of luster in the face and sallow complexion), pulmonary tuberculosis, and leukemia. In particular, it has been known to contain a relatively high amount of steroid glycosides and to have tonic effects, expectorant effects, blood pressure-lowering effects, effects of enhancing resistance and boosting red blood cells and blood pigments in an organism, and antibacterial properties. In addition, Codonopsis pilosula NANNF replenishes energy in the lungs and spleen and helps blood, so it helps the nasogastric system and supports the liver. The content of Codonopsis pilosula NANNF may be 10 to 45% by weight, more particularly 15 to 40% by weight, and even more particularly 15 to 30% by weight, based on dry weight.

[0109] White Hoelen is strengthens the spleen, acts as a sedative, calms fetal fever, and warms the body. It is effective for peptic ulcers, muscle spasms, thirst, vertigo, mental anxiety, and insomnia. It is a herbal medicine having tonic, diuretic, and sedative properties for use in treating kidney diseases, cystitis, and urethritis. It has an inhibitory effect on contact dermatitis. It has been used as a tonic since ancient times. It nourishes the spleen, expectorates phlegm, and stabilizes the mind. Pharmacological experiments have shown that it has diuretic, blood sugar-lowering, and sedative properties, and it is also known to revive immunity. It is also prescribed for vomiting, ascites, diarrhea, forgetfulness, and sleep disorders. It is also known to have excellent effects on diseases of the stomach, liver, pancreas, and kidneys, and is used as a medicine to treat people who are weak after suffering from illnesses and patients with chronic gastrointestinal diseases. It is also known to be effective on all sexually transmitted diseases and gynecological diseases, as well as toxic syndromes in men and women. The content of White Hoelen may be 10 to 20% by weight, more particularly 12 to 18% by weight, and even more particularly 13 to 17% by weight, based on dry weight.

[0110] Atractylodes macrocephala koidz is the dried root of the shovelwort plant and contains atractylol, atractylon, the volatile essential oil component hinesol and vitamins. It has been proven to lower blood sugar, stimulate gastric secretion and promote blood circulation, inhibit the reabsorption of tubules, promote sodium excretion and protect the liver, and is highly effective as a stomach tonic. It is also effective for sweating, fever, neuralgia, headache, and natal fever (to stabilize the fetus). According to the old medicine book, "Shennong's Classic of Herbal Medicine," it says, "If you want to live a long life, you must eat Atractylodes macrocephala koidz." The content of Atractylodes macrocephala koidz may be 5 to 20% by dry weight, more specifically 5 to 18% by dry weight, and more specifically 10 to 15% by dry weight.

[0111] Rehmanniae Radix is known in traditional Chinese medicine as categorized into fresh Rehmanniae Radix, dried Rehmanniae Radix, and steamed and dried Rehmanniae Radix. Steamed and dried Rehmanniae Radix is used as a blood booster and is used for menstrual irregularities, weak constitution, stunted growth in children, dementia, premature ejaculation, and erectile dysfunction; fresh Rehmanniae Radix is used for weak constitution, blood vomiting, nosebleeds, uterine bleeding, menstrual irregularities, and constipation; and dried Rehmanniae Radix is effective for thirst after fever and wasting-thirst caused by heat in the organs, and stops blood vomiting and nosebleeds. It also helps the reproductive function of the kidneys and regenerates the body's energy, so it plays a role in preventing or treating gray hair. The content of Rehmanniae Radix may be 5 to 15% by weight by dry weight, more particularly 5 to 10% by weight, and even more particularly 5 to 8% by weight.

[0112] Curcuma longa has long been consumed as a "royal tea" in the royal courts of China, Japan, Korea, and Europe, and it is recorded in the "Dongui Bogam" and "Bencao Gangmu" that "Curcuma longa promotes the detoxification of the liver and has excellent bile secretion and diuretic properties". The content of Curcuma longa may be 2 to 10% by weight, more particularly 3 to 8% by weight, and even more particularly 3 to 5% by weight based on dry weight.

[0113] Mentha arvensis contains 1-menthol, 1-limone isomenthone, camphene, and 1-methanol-D-glucoside, and its effects include dilating capillaries in the skin, antipyretic effect, vasorelaxation effect, cleansing the stomach, and inhibiting viruses. It also has anti-inflammatory, analgesic, stomachic, tonic, and diuretic properties, and appetite enhancement and fatigue recovery. The content of Mentha arvensis may be 2 to 10% by weight, more particularly 4 to 10% by weight, more particularly 5 to 8% by weight, based on dry weight.

[0114] The Polygonatum var., Astragalus membranaceus Bge., Artemisiae Scopariae Herba, Puerariae Radix, Codonopsis polisula NANNF, White Hoelen, Atractylodes macrocephala koidz, Rehmanniae Radix, Curcuma longa, and Mentha arvensis may be included in the form of extracts.

[0115] The Polygonatum var., Astragalus membranaceus Bge., Artemisiae Scopariae Herba, Puerariae Radix, Codonopsis polisula NANNF, White Hoelen, Atractylodes macrocephala koidz, Rehmanniae Radix, Curcuma longa, and Mentha arvensis may be included in the form of a liquid component obtained by immersing them in a solvent and then extracting them for a period of time at room temperature or at a warm temperature. The solvent may be one or more solvents selected from the group consisting of, but not limited to, water, alcohols of C1 to C4, organic solvents, and mixtures thereof.

[0116] The dibenzo-p-dioxin derivative may comprise a compound represented by one or more chemical formulae selected from the group consisting of:

[0117] [Formula 1]

[0118]

[0119] [Formula 2]

[0120]

[0121] [Formula 3]

[0122]

[0123] [Formula 4]

[0124]

[0125] [Formula 5]

[0126]

[0127] [Formula 6]

[0128]

[0129] [Formula 7]

[0130]

[0131] [Formula 8]

[0132]

[0133] [Formula 9]

[0134]

[0135] [Formula 10]

[0136]

[0137] In the above formula, each R is hydrogen, alkyl, alkenyl, phenyl, phenylalkyl, alkanoyl, hydroxyphenyl, dihydroxyphenyl, or acyl. Preferably, each R is H.

[0138] "Alkyl" is the monovalent part obtained by the removal of a hydrogen atom from a carbon atom of an aliphatic or alicyclic, saturated or unsaturated (unsaturated, completely unsaturated) hydrocarbon compound, wherein a saturated alkyl may include, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and the like, a saturated straight-chain alkyl may include, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl (amyl), n-hexyl, n-heptyl, and the like, a saturated branched-chain alkyl may include, for example, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, and the like.

[0139] "Alkenyl" is an alkyl with one or more carbon-carbon double bonds, wherein examples of unsaturated alkenyl groups may include ethenyl (vinyl, -CH=CH2), 1-propenyl (-CH=CHCH3), 2-propenyl, isopropenyl, butenyl, pentenyl, and hexenyl.

[0140] "Alkanoyl" means a lower alkyl group bonded via a carbonyl group, including, for example, acetyl groups, propionyl groups, and the like.

[0141] An "acyl" or "acyl group" is the atomic group remaining, for example, after subtraction of OH, the carboxylic group of a carboxylic acid, and is generally denoted by RCO. R is one or more substituents, and is not limited as long as it may be capable of binding to the CO. When R is an aromatic atom, it is sometimes specifically referred to as an "aroyl", but it is also a type of acyl group. Examples of acyl groups include, but are not limited to, formyl (HCO-), acetyl (CH3CO-), propionyl (C2H5CO-), butyryl (C3H7CO-), valeryl (C4H9CO-), pentanoyl (CH3(CH2)3CO-), palmitoyl (C15H31CO-), stearoyl (C17H33CO-), oleoyl (C17H31CO-), oxalyl (-CO-CO-), malonyl (-COCH2CO-), succinyl (-CO(CH2)2CO-), benzoyl (C6H5CO-), toluoyl (CH3-C6H4-CO-), salicyloyl (HO-C6H4-CO-), cinnamoyl (C6H5CH＝CHCO-), naphthoyl (C10H7CO-), phthaloyl (CO-C6H4-CO-), furoyl (C5H3O2-), undecanoyl (CH3(CH2)9CO-), and docosenoyl with the OH group removed from docosenoic acid.

[0142] The present invention may include "pharmaceutically acceptable salts" of the compounds.

[0143] A "pharmaceutically acceptable salt" may be an acid adduct salt formed by a pharmaceutically acceptable free acid, wherein the free acid may be an organic or inorganic acid.

[0144] The organic acids include, but are not limited to, citric acid, acetic acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, trifluoroacetic acid, benzoic acid, gluconic acid, methanesulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, glutamic acid, and aspartic acid. The inorganic acids also include, but are not limited to, hydrochloric acid, bromic acid, sulfuric acid, and phosphoric acid.

[0145] For example, if a compound is an anion or has a functional group that can be an anion (e.g., -COOH can be -COO-), it can form a salt with a suitable cation. Examples of suitable inorganic cations include, but are not limited to, alkali metal ions, such as Na+and K+, alkaline earth metal cations, such as Ca2+and Mg2+, and other cations, such as Al3+. Examples of suitable organic cations include, but are not limited to, ammonium ions (e.g., NH4+) and substituted ammonium ions (e.g., NH R3+, NH2R2+, NHR3+, NR4+).

[0146] Some examples of suitable substituted ammonium ions are those derived from not only ethylamine, diethylamine, dicyclohexylamine, triethylamine, butylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, benzylamine, phenylbenzylamine, choline, meglumine, and tromethamine, but also amino acids, such as lysine and arginine. A typical example of a quaternary ammonium ion is N(CH3)4+.

[0147] If the compound is a cation or has a functional group that can be a cation (e.g., -NH2can be -NH3+), it can form a salt with a suitable anion. Examples of suitable inorganic anions include, but are not limited to, those derived from the following inorganic acids: hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfurous acid, nitric acid, nitrite, phosphoric acid, and phosphorous acid.

[0148] Examples of suitable organic anions include, but are not limited to, those derived from the following organic acids: 2-acetoxybenzoic acid, acetic acid, ascorbic acid, aspartic acid, benzoic acid, camptosulfonic acid, cinnamic acid, citric acid, edetic acid, ethanedisulfonic acid, ethanesulfonic acid, fumaric acid, glucheptonic acid, gluconic acid, glutamic acid, glycolic acid, hydroxymaleic acid, hydroxynaphthalene carboxylic acid, isethionic acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, methanesulfonic acid, mucilage acid, oleic acid, oxalic acid, palmitic acid, palmic acid, pantothenic acid, phenylacetic acid, phenylsulfonic acid, propionic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, sulfanilic acid, tartaric acid, toluenesulfonic acid, and valeric acid. Examples of suitable polymeric organic anions include, but are not limited to, those derived from the following polymeric acids: tannic acid, carboxymethyl cellulose, and the like.

[0149] The dibenzo-p-dioxin derivatives may be included in the composition of the present invention as a single compound or as a combination of two or more of such compounds, for example, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more compounds.

[0150] The dibenzo-p-dioxin derivatives may be included in an amount of 0.1 to 5% by weight, more particularly 0.2 to 4% by weight, more particularly 0.3 to 3% by weight, based on the total weight of the composition.

[0151] The dibenzo-p-dioxin derivatives may include, based on their content in the composition, the following:

[0152] (a) 0.1 to 6% by weight of the dibenzo-p-dioxin derivative of Formula 1;

[0153] (b) 5 to 60% by weight of the dibenzo-p-dioxin derivative of Formula 2;

[0154] (c) 1 to 30% by weight of dibenzo-p-dioxin derivative of Formula 3;

[0155] (d) 0.5 to 80% by weight of dibenzo-p-dioxin derivative of Formula 4;

[0156] (e) 0.1 to 10% by weight of a dibenzo-p-dioxin derivative of Formula 5;

[0157] (f) 0.5 to 15% by weight of a dibenzo-p-dioxin derivative of Formula 6;

[0158] (g) 0.1 to 5% by weight of a dibenzo-p-dioxin derivative of Formula 7;

[0159] (h) 0.1 to 5% by weight of a dibenzo-p-dioxin derivative of Formula 8;

[0160] (i) 0.1 to 10% by weight by weight of a dibenzo-p-dioxin derivative of Formula 9; and

[0161] (j) 0.1 to 12% by weight of dibenzo-p-dioxin derivative of Formula 10.

[0162] Suitable dibenzo-p-dioxin derivatives can be extracted from, for example, Eisenia bicyclis, Eisenia arborea, Eisenia desmarestioides, Eisenia galapagensis, Eisenia masonii, Ecklonia kurome, Ecklonia cava, Ecklonia stolonifera, Ecklonia maxima, Ecklonia radiata, Ecklonia bicyclis, Ecklonia biruncinate, Ecklonia buccinalis, Ecklonia caepaestipes, Ecklonia exasperta, Ecklonia fastigiata, Ecklonia brevipes, Ecklonia arborea, Ecklonia latifolia, Ecklonia muratii, Ecklonia radicosa, Ecklonia richardiana, or Ecklonia wrightii. Preferably, the dibenzo-p-dioxin derivatives may be extracted from brown algae such as Eisenia bicyclis, Ecklonia cava, Ecklonia kurome or Ecklonia stolonifera.

[0163] The polyphenolic compound may include a compound of Formula 11:

[0164] [Formula 11]

[0165]

[0166] wherein n can be 2 to 50, more specifically 5 to 48, and even more specifically 10 to 46.

[0167] The fatty liver may include, for example, alcoholic or non-alcoholic fatty liver. Non-alcoholic fatty liver is defined as a liver disorder characterized by hepatic fat accumulation primarily of metabolic origin, resembling alcoholic liver disease histologically, despite the absence of significant alcohol consumption, and is defined as including both simple fatty liver with a favorable prognosis and advanced non-alcoholic steatohepatitis.

[0168] "Treatment" refers to any objective or subjective parameters, for example, any sign of success in reduction; remission; the creation of more tolerable symptoms or damage for the patient, reduction in the pathology or condition; slowing the rate of deterioration or decline; creation of a less debilitating final point of decline; treatment or improvement in damage, pathology, or condition including improvement of the patient's physical or mental well-being. Treatment or improvement of symptoms may be based on objective or subjective parameters including physical examination, neuropsychiatric examination, and / or psychiatric evaluation.

[0169] An "effective amount" is generally an amount sufficient to reduce the severity or frequency of a symptom, eliminate a symptom and its underlying cause, prevent the occurrence of a symptom or its underlying cause, or ameliorate or correct an impairment resulting from or related to a disease state. In some embodiments, an effective amount is a therapeutically effective amount or a prophylactically effective amount. A "therapeutically effective amount" is an amount sufficient to correct a disease state or symptom, particularly a condition or symptom associated with a disease state, or to prevent, hinder, delay, or reverse the progression of a disease state or any other undesirable symptom associated in any way with a disease state. A "prophylactic effective amount" is an amount of a pharmaceutical composition that, when administered to a subject, has the intended prophylactic effect, e.g., prevention or delay of the onset of a disease state, or reduction in the likelihood of the onset (or recurrence) of a disease state or associated symptoms.

[0170] The composition of the present invention may be a pharmaceutical composition. The pharmaceutical composition may be administered by any route. The composition of the present invention can be provided to an animal by any suitable means, either directly (e.g., locally, by injection, implantation, or topical administration to a tissue site) or systemically (e.g., parenterally or orally). When the composition of the present invention is administered parenterally, such as intravenously, subcutaneously, ophthalmicly, intraperitoneally, intramuscularly, orally, rectally, intraorbitally, intracerebrally, intracranially, intraspinally, intraventricularly, intrathecally, intracistenally, intracapsularly, intranasally, or by aerosol administration, the pharmaceutical composition may comprise, for example, a portion of an aqueous or physiologically applicable body fluid suspension or solution. Accordingly, a carrier or vehicle is physiologically acceptable and can be added to the composition and delivered to the patient. Thus, a carrier such as a body fluid for a formulation may typically include normal saline.

[0171] As for the frequency of administration, the clinician will typically administer the pharmaceutical composition until a dose achieves the intended effect. Thus, the pharmaceutical composition may be administered as a single dose, as two or more time-spaced doses, or as a continuous administration by an implanted device or catheter. Further refinement of the appropriate dosage is routinely made by those skilled in the art and falls within the scope of work routinely performed by them.

[0172] The preferred route may vary, for example, depending on the condition of the recipient. If administered orally, it may be formulated as a pill, capsule, tablet, or the like, with a pharmaceutically acceptable carrier, glydent, or excipient. If administered parentally, it can be formulated as an unit dose injection, in combination with a pharmaceutically acceptable parenteral vehicle or diluent. The composition of the present invention can be administered by any route suitable for the condition to be treated. Suitable routes include oral, parenteral (including subcutaneous, intramuscular, intravenous, intraarterial, inhalation, intradermal, intrathecal, intradural, and injection techniques), transdermal, rectal, intranasal, topical (including cheek and sublingual), vaginal, intraperitoneal, intrapulmonary, and intranasal administration. Topical administration may include utilizing transdermal administration, such as transdermal patches or iontophoresis devices.

[0173] The unit dose is 0.01 μg / kg to 100 mg / kg in humans, more specifically 1 μg / kg to 10 mg / kg. Although these amounts are optimal, they may vary depending on the disease to be treated and the presence or absence of side effects, and the optimal dosage can be determined using conventional experiments. Administration of the fusion protein may be by periodic bolus injections or by continuous intravenous, subcutaneous, or intraperitoneal administration from an external reservoir (e.g., intravenous bag) or internal (e.g., bioerodable implant) source.

[0174] In another aspect, the present invention relates to a health functional food for the prevention or amelioration of fatty liver. The composition of the health functional food is as described above.

[0175] "Health functional food" means a food manufactured and processed using raw materials or ingredients that have functional properties useful to the human body in accordance with the Health functional food Act No. 6727, and "functional" means consumed for the purpose of obtaining effects useful for health purposes, such as regulating nutrients or physiological actions on the structure and function of the human body.

[0176] The composition may contain conventional food additives, and its suitability as a "food additive" is determined in accordance with the standards and specifications for the item concerned, based on the General Rules and General Test Methods of the Food Additive Code approved by the Ministry of Food and Drug Safety.

[0177] The items listed in the "Food Additive Code" include, for example, chemical synthetics such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon color, licorice extract, microcrystalline cellulose, safflower color, and guar gum; mixed preparations such as L-glutamic acid sodium salt preparations, alkaline preparations for noodles, preservative preparations, and tar color preparations.

[0178] The health functional food may be prepared and processed in the form of, but not limited to, tablets, capsules, powders, granules, liquids, beverages, pills, and the like. They can be prepared by conventional methods with the addition of additives required for each formulation.

[0179] The present invention will now be described in more detail with reference to the following examples. These examples are intended solely to illustrate the present invention, and it will be apparent to one of ordinary skill in the art that the scope of the present invention is not to be construed as limited by these examples.

[0180]

[0181] Preparation Example 1: Preparation of a composition

[0182] The composition according to the present invention comprise the following (hereinafter, the composition of Preparation Example 1, or SBD X2 in FIGs. 1a and 1b):

[0183]

[0184] Seapolynol includes compounds of formulae 1 to 10, wherein R is all H.

[0185] [Formula 1]

[0186]

[0187] [Formula 2]

[0188]

[0189] [Formula 3]

[0190]

[0191] [Formula 4]

[0192]

[0193] [Formula 5]

[0194]

[0195] [Formula 6]

[0196]

[0197] [Formula 7]

[0198]

[0199] [Formula 8]

[0200]

[0201] [Formula 9]

[0202]

[0203] [Formula 10]

[0204]

[0205] The compounds of Formulae 1 to 10 are included in the following proportions based on their contents in the composition:

[0206] (a) 5.2% by weight of the dibenzo-p-dioxin derivative of Formula 1;

[0207] (b) 29.7% by weight of the dibenzo-p-dioxin derivative of Formula 2;

[0208] (c) 2.0% by weight of the dibenzo-p-dioxin derivative of Formula 3;

[0209] (d) 20.1% by weight of the dibenzo-p-dioxin derivative of Formula 4;

[0210] (e) 8.4% by weight of the dibenzo-p-dioxin derivative of Formula 5;

[0211] (f) 13% by weight of the dibenzo-p-dioxin derivative of Formula 6;

[0212] (g) 4.5% by weight of the dibenzo-p-dioxin derivative of Formula 7;

[0213] (h) 4% by weight of the dibenzo-p-dioxin derivative of Formula 8;

[0214] (i) 3.1% by weight of a dibenzo-p-dioxin derivative of Formula 9; and

[0215] (j) 10% by weight of dibenzo-p-dioxin derivative of Formula 10.

[0216]

[0217] Example 1: Evaluating efficacy through in vivo studies in a fat mouse model

[0218] A three-week period was designated to allow the animals to be isolated and acclimatised to the animal room environment for long-term studies. All animal use procedures were conducted in accordance with the National Institutes of Health and U.S. Department of Agriculture Guide for the Care and Use of Animals and were approved by the Animal Care and Use Committee. Female C57BL / 6J-Lep ob (6-8 weeks old, the Jackson Laboratory, Bar Harbor, ME) were used.

[0219] Controls were provided with normal drinking water and water bottles were changed every other day. The group fed the composition of Preparation Example 1 was divided into two groups, the first group started on the same date as the control group, and the second group started one month later. A third animal was fed the composition of Preparation Example 1 for 30 days and ordered for further histological studies.

[0220] The amount of the composition of Preparation Example 1 ingested in each cage of four animals was recorded twice weekly. Control mice were fed water and commercially available mouse chow (PMI Nutritional Interntl. Co. Brentwood, MO). Mice fed the composition of Preparation Example 1 were fed the same chow. Table 2 lists all experimental groups and feeding schedules.

[0221]

[0222] Clinical examination and weight measurement

[0223] Animals were observed every morning. Animals were examined and weighed only on a weekly basis to minimize disturbance to the animals. Body weight was recorded independently and any abnormalities were noted. At the end of the experiment, animal necropsies were performed.

[0224] Anatomy for histology

[0225] Animal tissues were collected for necropsy. Tissue organs were selected and excised for histology. Tissues were fixed in 10% neutral buffered formalin. After 24 hours of fixation, the tissues were dehydrated and embedded in paraffin blocks. The paraffin blocks were sectioned and two levels of each block separated by a distance of 500 μm were selected and eight slides were made from each level. Two slides were stained with haematoxylin and eosin to examine histopathology, and Periodic acid Schiff (PAS) to identify carbohydrates in the tissue and Masson's trichrome stain to identify collagen deposition in the tissue were conducted.

[0226] Organ tissue harvesting

[0227] At necropsy, the desired organs were surgically excised using a scalpel. The harvested organs were placed in appropriate and properly labelled jars containing 10% natural buffered formalin (NBF). The jars were labelled with a coded numbering system.

[0228] Histology / Morphology

[0229] Mouse tissues were removed immediately after sacrifice. Tissues were fixed in 0.1 M sodium cacodylate with 2% glutaraldehyde or 1% paraformaldehyde. Buffer (pH 7.4) and buffered formalin fixative were used for fixing for 2-4 hours at room temperature. The volume of fixative used was determined by the volume displacement method. The fixed tissues were stored in the fixative at 4°C overnight. Tissues were selected at the same similar level for comparison accordingly. Tissues were then cut into 1-2 cm slices at similar locations on the same tissue and subdivided into blocks for light microscopy studies.

[0230] Tissue blocks dehydrated in ethanol were embedded in paraffin. 5 μm sections were cut from each block with a knife, stained with H&E, PAS, and Masson's Trichrome, and examined under a PMRB Leica microscope. Histomorphometry of adipose tissue analysis was conducted. At least 10 fields were randomly selected for examination by light microscopy. Individually blinded 2X5 μm tissue sections according to the protocol design throughout the 500 μm thickness were selected. Each field was examined at a magnification of X200 using a Whipple Micrometer disc (Bausch & Lomb, Rochester, NY) representing 2,200 μm^2 of tissue area.

[0231] Statistical analysis of cell count data

[0232] SigmaStat software was used for all statistical analyses, and SigmaPlot vs. 4 was used for all graphical representations of the data. In general, analysis of variance (ANOVA) was used for Dunn's pairwise comparisons to determine statistical differences at the p>0.001 level.

[0233] Mice fed the diet for 4 months lost an average of 3 g in weight (10%) (FIGs. 1A and 1B) and showed a decrease in body fat content. In contrast, control mice fed water and normal chow continued to gain weight and obesity (FIGs. 1A and 1B). Body weight was clearly altered by feeding the composition of Preparation Example 1.

[0234]

[0235] A shunt in glucose metabolism between muscle and fat. Fat metabolism and sugar homeostasis are intrinsically linked. Blood glucose test records are shown in the following Table 4 and Table 5. The composition of Preparation Example 1 can reduce the sugar content in the blood of mice. However, all blood glucose contractions in C57BL mice are within the normal range (Tables 6 and 7).

[0236]

[0237]

[0238]

[0239]

[0240] Histological analyses of adipose tissue, muscle, liver, and pancreas were selected after feeding the composition of Preparation Example 1 for 30, 60, and 120 days. Mice fed water only accumulated fat in muscle, liver and pancreas throughout the 120-day feeding period. Compared to controls, mice fed the composition of Preparation Example 1 had less fat deposition in muscle, liver, and pancreatic tissue and cells or fewer adipocytes around blood vessels (FIGs. 2, 6, 11). A reversal of fat deposition in liver hepatocytes and pancreatic acinar cells (FIGs. 3, 4) was observed in the group fed the composition of Preparation Example 1. In addition, the lipid content of skeletal muscle cells was significantly lower in the group fed the composition of Preparation Example 1 compared to the control group (FIGs. 3, 7, 8, 12). The decrease in adipocyte and fat uptake and the resulting decrease in adipocyte number were consistent throughout the feeding period. Fat mice fed the composition of Preparation Example 1 were more active and alert than control fat mice. It is likely that feeding the composition of Preparation Example 1 induced an increase in physical activity, as observed frequently during the experimental period.

[0241] The decrease in the number of adipocytes in the tissues induced by the composition of Preparation Example 1 and the association with blood vessels indicate that the liver, muscle and adipose tissues are involved in glucose homeostasis in terms of weight loss. Feeding the composition of Preparation Example 1 allowed for coordinated activity through metabolic integration of adipose tissue. Adipose is involved in fatty acid oxidation, taste response, lipogenesis and lipid storage. After 120 days of administration of the composition of Preparation Example 1, a reduction in adipocytes was evident in skeletal muscle, adipose tissue and pancreatic acini (FIGs. 5, 9, 14).

[0242] The histology of the organs important for fat metabolism analyzed in the feeding of the composition of Preparation Example 1 and each organ were analyzed for each study period. The organs observed were as follows

[0243] Adipose tissue

[0244] Adipose tissue (fat) is a special type of loose fibrous connective tissue that contains a large number of adipocytes. Adipocytes store fat droplets in their cytoplasm, causing them to increase in size and lopsided nuclei (FIGs. 2A, B, C, D). In fat mice, fat is found throughout the body but is concentrated in the subcutaneous layer of the skin, on the surface of the heart, around joints, in the breasts of sexually mature females, and around the kidneys and intestines. However, in mice, fat functions not only as a food reserve, but also as a burden on various organs.

[0245] After 30 days, animals fed the composition of Preparation Example 1 had little difference in adipose tissue compared to controls (FIGs. 2A, B). After 30 days of feeding, fat animals show abundant adipose tissue in the abdomen and around internal organs. The adipocytes are densely packed and separated by loose, irregular, thin connective tissue (FIG. 2A). Individual adipocytes appear as empty cells. The fat has been lysed by chemical solutions used during routine histological preparation (FIG. 2B).

[0246] The nucleus is compressed at the peripheral rim of the cytoplasm. Small blood vessels (arrows) are frequently distributed in the adipose tissue (FIGs. 2A, B). After feeding with the composition of Preparation Example 1 for 30 days, the adipose tissue shows that the adipocytes are slightly packed and the cytoplasmic membrane is loose and less tight. Many fibroblasts are visible. In addition, there are fewer small blood vessels in the adipose tissue (FIGs. 2C, D).

[0247] On the 60th day of feeding, the animal adipose tissue shows differences between the two groups of fat mice. Fat is observed in the abdominal cavity, and is accumulated to a greater extent on the surface and walls of internal organs of fat mice not administered with the composition of Preparation Example 1. High concentrations of fat are also observed in the abdominal omentum. The adipose tissue contains typical adipocytes of a more regular shape with many blood vessels (FIG. 5A).

[0248] The adipocytes of mice fed the composition of Preparation Example 1 have a varied shape and are filled with cell membranes with few fat droplets. Fibroblasts present in the fat are abundant (FIG. 5B). This indicates that the adipocytes are resorbed and more fibroblasts are seen in the loose connective tissue. Feeding the composition of Preparation Example 1 contributes to this phenomenon.

[0249] In a 120-day study of feeding the composition of Preparation Example 1, there is a change in the expression of the number of vessels per unit area of adipose tissue (FIG. 11A, B). Adipose tissue is shown to have more blood vessels and capillaries in the control group (FIG. 11A) compared to the group fed the composition of Preparation Example 1. In the group fed the composition of Preparation Example 1, adipose tissue had fewer blood vessels and capillaries (FIG. 11B).

[0250] Skeletal muscle

[0251] The primary function of muscle tissue in the animal body is to produce movement. Muscle tissue is composed of elongated cells called fibres (FIGs. 3A, B), the cytoplasm of which contains different amounts of contractile protein filaments called actin and myosin.

[0252] The effect of feeding the composition of Preparation Example 1 to skeletal muscle was studied. Skeletal muscle is attached to many bones and moves them accordingly. Normal skeletal muscle is long, multinucleated fibres. The longitudinal and parallel arrangement of fibres is held together by connective tissue (FIGs. 3, 7, 8). Skeletal muscle is innervated by large motor nerves and all skeletal muscle fibres are innervated; however, in fat mice, it is affected by the invasion of adipocytes.

[0253] Increased intercellular adipocytes in skeletal muscle in fat mice are frequently observed during the feeding period. The parenchymal cells of the tissue take up excess fat, and fatty changes occur in connective tissue cells. Lipid metabolism involves many complex enzymatic pathways, receptors, and molecular binding. Muscle and adipose tissues are the main sites of triglyceride supply. During the period of feeding the composition of Preparation Example 1, the following was observed:

[0254] 1. Mice fed water and normal mouse chow after 30 days: Fat mice exhibited an abundance of adipocytes (fat) between muscle fibres. The adipocytes infiltrated between the muscle fibres (FIG. 3A). In the muscle fibres of the fat mice, the muscle tissue was separated from the muscle fibres by abundant adipocytes. Neurons are visible in the adipocytes. In the group fed the composition of Preparation Example 1, there are significantly fewer adipocytes between muscle fibres (FIG. 3B). Adipocytes of various sizes are closely attached to the muscle fibres, indicating lipid reabsorption. The collagen in the bundles appears normal.

[0255] 2. On day 60 of feeding, control fat mice show the development of adipocytes in the intramuscular fibres as shown in animals fed a 30-day diet. The adipocytes are located around blood vessels and muscle. Masson's trichrome-stained sections also show the association of adipose tissue with blood vessels. Neurons in muscle are closely associated with muscle fibres, but not in fat mice (FIGs. 7A, B). The effect of feeding the composition of Preparation Example 1 on inhibiting adipocytes is observed to a much lesser extent compared to the control fed animals.

[0256] Feeding the composition of Preparation Example 1 is a peripheralisation or inhibition of adipocyte development. Feeding the composition of Preparation Example 1 in fat mice results in increased lipid uptake, resulting in a decrease in the number of adipocytes in the intermuscular fibres (FIGs. 8A, B, C). The adipocytes vary in size and thick collagen deposition indicates that there is lipid reabsorption in the adipocytes (FIG. 8A, B, C).

[0257] After 120 days of feeding, the difference between the group fed the composition of Preparation Example 1 and the control group was significant (FIGs. 12A and 12B). In the feeding of the composition of Preparation Example 1, the muscle fibres show only a small number of fat cells. The fat cells were observed to be closely associated with blood vessels. Some of the muscles of the fed animals showed few hepatic fat cells (FIG. 12B).

[0258] Liver

[0259] Liver is an endocrine and exocrine organ, and hepatocytes secrete bile in the bile ducts. The bile salts present in bile are necessary to emulsify fats that enter the small intestine from the stomach. The bile helps pancreatic lipase to digest fat. The liver also stores glycogen and fat. The histological structure and cellular composition of the mouse liver is the same as in humans. Because the liver and lipids have a very close relationship, both physiologically and pathologically, the liver was chosen as one of the important organs to analyze the composition experiments of Preparation Example 1.

[0260] The smallest unit in the liver is the hepatic artery, and the portal central vein contains blood partially provided with oxygen. Fat storage in the liver is due to changes in the metabolic activity of hepatocytes. The accumulation of fat in the liver in fat mice is due to the fact that many liver enzymes enable the metabolism of fats and carbohydrates; therefore, the increased adaptability of the enzymes produces more glycerophosphate, which is then converted into triglyceride fats in the cells. Fat mice may have an imbalance in fat oxidation mechanisms. Reduced oxidation of fatty acids leads to their conversion to fat. Fat mice fed the composition of Preparation Example 1 or a control diet did not show local fibrosis.

[0261] 1. The livers of control fat mice fed for 30 days show that the liver cells contain fat droplets (FIG. 4A). However, in the group fed the composition of Preparation Example 1, there are significantly fewer fat droplets in the hepatocytes. Therefore, a reduction in fatty liver is observed in the group fed the composition of Preparation Example 1 (FIG. 4B).

[0262] 2. After 60 days of feeding, the control mice fatty livers show that the hepatocytes have vacuoles in the cytoplasm (FIG. 9A). The fatty liver is more obvious than at 30 days. However, in the group fed the composition of Preparation Example 1, the hepatocytes show very scaly fat droplets and glycogen deposition is seen in some hepatocytes (FIG. 9B).

[0263] 3. In the 120-day feeding experiment, the hepatocytes of the control group showed a marked accumulation of fat droplets in the cytoplasm (FIG. 13A). However, in the group fed the composition of Preparation Example 1, there was little or no fat accumulation in the cytoplasm of the hepatocytes (FIG. 13B).

[0264] Pancreas

[0265] The pancreas was chosen as an important organ to analyze the effect of feeding the composition of Preparation Example 1 because it is a major accessory digestive organ. The pancreas produces a variety of digestive enzymes that break down fats, carbohydrates, and proteins into smaller molecules. The majority of the pancreas is composed of exocrine acinar cells that secrete pancreatic enzymes. The pancreas secretes large amounts of digestive enzymes in response to the presence of fat in the small intestine. Pancreatic enzymes are produced by acinar cells. In the acinar cells which are secreted from the pancreas, pancreatic islets, which are pale-coloured, spherical cellular units, are interspersed. These islets function as the endocrine system. Islet cells produce two very important hormones: insulin and glucagon. Glucagon increases the level of glucose in the blood. This functions are achieved by accelerating the conversion of glycogen, amino acids, and fatty acids into glucose in the liver, thereby raising blood sugar. The beta cells of the islets produce insulin. It is very closely related to obesity in the release, which is stimulated by the rise in glucose after feeding. The main physiological function of insulin is to transport glucose into the cells of the liver, muscle and fat, thereby lowering the glucose level in the bloodstream.

[0266] 1. The histology of the pancreas in the 30-day feeding experiment shows that low cuboidal epithelial cells were lined in the small intra-lobular duct, and adipose tissues were distributed in the pancreatic vessels. Adipose tissue was infiltrated between pancreatic lobules (FIG. 5A). Although adipocytes were not involved in the pancreatic sublingual glands or acini, they easily cause acute pancreatitis by lipase which causes adipocyte necrosis. When the composition of Preparation Example 1 is fed, the pancreas does not show adipose tissue accumulation. Few fat droplets were occasionally observed only in the acini (FIG. 5B).

[0267] 2. Fat mice fed the composition of Preparation Example 1 for 60 days show significantly reduced fat accumulation in the pancreas (FIGs. 10A, B). Mice fed the composition of Preparation Example 1 for 60 days showed reduced fat droplets in the salivary glands, which are devoid of adipocytes associated with the islets of Langerhans (FIG. 10C).

[0268] 3. Feeding the composition of Preparation Example 1 for 120 days shows a significant beneficial effect on adipocyte reduction in the pancreas of fatty mouse model. After 4 months, the pancreatic and sublingual glands in the control fatty mice show an association with adipocyte infiltration (FIG. 14A). However, the pancreas of animals fed the composition of Preparation Example 1 showed normal appearance of both endocrine islets and acini (FIG. 14B).

[0269]

[0270] Preparation Example 2: Preparation of a composition

[0271] The composition of the present invention includes the following:

[0272]

[0273] Seapolynol includes compounds of formulae 1 to 10, wherein R is all H.

[0274] [Formula 1]

[0275]

[0276] [Formula 2]

[0277]

[0278] [Formula 3]

[0279]

[0280] [Formula 4]

[0281]

[0282] [Formula 5]

[0283]

[0284] [Formula 6]

[0285]

[0286] [Formula 7]

[0287]

[0288] [Formula 8]

[0289]

[0290] [Formula 9]

[0291]

[0292] [Formula 10]

[0293]

[0294] The compounds of Formulae 1 to 10 are included in the following proportions based on their content in the composition:

[0295] (a) 5.2% by weight of the dibenzo-p-dioxin derivative of Formula 1;

[0296] (b) 29.7% by weight of the dibenzo-p-dioxin derivative of Formula 2;

[0297] (c) 2.0% by weight of the dibenzo-p-dioxin derivative of Formula 3;

[0298] (d) 20.1% by weight of the dibenzo-p-dioxin derivative of Formula 4;

[0299] (e) 8.4% by weight of the dibenzo-p-dioxin derivative of Formula 5;

[0300] (f) 13% by weight of the dibenzo-p-dioxin derivative of Formula 6;

[0301] (g) 4.5% by weight of the dibenzo-p-dioxin derivative of Formula 7;

[0302] (h) 4% by weight of the dibenzo-p-dioxin derivative of Formula 8;

[0303] (i) 3.1% by weight by weight of a dibenzo-p-dioxin derivative of Formula 9; and

[0304] (j) 10% by weight of dibenzo-p-dioxin derivative of Formula 10.

[0305]

[0306] Example 2: Investigating the impact on function and overall health

[0307] To check whether the composition of the present invention has a beneficial effect on liver function and overall health, 70 normal volunteers aged 40-65 years, whose livers may be under stress, were asked to participate in a clinical trial.

[0308] Participants were individuals between the ages of 40 to 65, mostly from high-income households, working in stressful work environments, and those who had or tended to have high cholesterol, fatty deposits around the liver, and a high likelihood of having insulin resistance. There were 70 participants (men and women), with an average age of 49.

[0309] The study procedure is as follows:

[0310] (1) Health assessment

[0311] Participants underwent health assessments (blood tests and fiber scans) at various time points: baseline, 12 weeks, 16 weeks, and 6 months.

[0312] Blood samples were taken to assess liver function, kidney function, cholesterol levels, and glycated hemoglobin (a biomarker of blood sugar levels and diabetes). A FibroScan, which measures liver stiffness, was performed to check for liver fibrosis (scarring) and liver fat content.

[0313] Participants were instructed to consume one bottle of the composition of Preparation Example and a glass of water per day for the duration of the study, while continuing to maintain their usual habitual lifestyle and diet without any changes. All participants were contacted via phone call every other week to discuss the effectiveness of the composition and their overall well-being. Participants were asked to submit weekly online surveys that included questions related to food and alcohol consumption. Participants were asked to submit weekly online surveys that included questions related to their exercise routine, sleep quality, mental clarity, energy, and stress levels.

[0314] (2) Blood assessment results

[0315] All participants' kidney function and glucose levels were in the normal range at baseline and remained in the normal range at all intervals.

[0316] Compared to baseline, in the liver profile,

[0317] 1) ALT value

[0318] 90% of participants showed improvement in their measurements.

[0319] 10% of participants showed deterioration in their measurements.

[0320] 2) AST numbers

[0321] 91% of participants showed improvement in their measurements.

[0322] 9% of participants showed deterioration in their measurements.

[0323] 3) GGT Level

[0324] 72% of participants showed improvement in their levels.

[0325] 28% of participants showed improvement in their measurements.

[0326] In the lipid profile,

[0327] 1) Cholesterol levels

[0328] 77% of participants showed improvement in their measurements.

[0329] 23% of participants showed deterioration in their measurements.

[0330] 2) Triglyceride levels

[0331] 82% of participants showed improvement in their measurements.

[0332] 18% of participants showed deterioration in their measurements.

[0333] 3) LDL levels

[0334] 59% of participants showed improvement in their measurements.

[0335] 41% of participants showed deterioration in their measurements.

[0336] (3) Fibroscan report

[0337] 1) Participants' liver stiffness remained at normal levels throughout the study.

[0338] 2) At the baseline:

[0339] 56% of participants had excess fat deposits around the liver (steatosis grade 1 or higher). 31% of participants had a fatty liver (CAP score >248). 24% of participants had fatty liver disease (CAP score is 260 or more).

[0340] 3) Comparison of the first and second fiberscans:

[0341] 82% of participants with fatty liver had a decrease in liver fat after the test. 88% of participants with fatty liver disease had a reduction in liver fat after the test. 41% of participants with excess fatty deposits around the liver had a reduction in liver fat to within normal range. The trial was ended.

[0342] (4) Response results based on the questionnaire

[0343] All participants reported improved sleep patterns with reduced anxiety. 90% of participants reported increased energy levels. 80% of participants reported improvements in cognition and memory. One-off evidence of improved skin, digestion, bowel flow, and reduced inflammation was also reported.

[0344] Consuming one bottle per day for eight weeks has been shown to have a positive effect on blood biomarkers such as cholesterol levels, triglycerides, and liver enzymes. Studies have also shown that the composition can reduce liver fat and prevent fatty liver disease and fibrosis, and has positive effects on cognition and sleep.

[0345]

[0346] Example 3: Liver function assessment

[0347] To monitor liver health over a two-year period, participants were given liver scans using a fibroscan machine and blood tests for liver function. Fibroscan works by measuring the speed of ultrasound waves traveling through the liver to identify fatty changes in liver tissue. The commonly used blood test measures the levels of two liver function enzymes, AST and ALT. When the liver is damaged, AST and ALT are released into the bloodstream, so increased levels of both enzymes indicate liver damage.

[0348] There were 66 participants in the study (14 women and 52 men), mostly from high-income households.

[0349] 1. Study procedures:

[0350] (1) Health assessment:

[0351] Participants underwent liver health assessments (fiber scan and blood tests) at various time points: baseline, 3, 6, and 12 months.

[0352] Fiber scans were measured by CAP scores:

[0353] - Normal liver fat: CAP score <248

[0354] - Fatty liver: CAP score >248

[0355] - Fatty liver disease: CAP score >260

[0356] (2) Liver Fat (CAP)

[0357]

[0358] Blood tests were measured in IU / L: Normal AST range: 0-37, Normal ALT range: 10-50 for men; Normal AST range: 0-31, Normal ALT range: 10-35 for women.

[0359] Participants consumed one bottle of the composition per day with a glass of water and continued to maintain their habitual lifestyle and diet without any changes.

[0360]

[0361] 2. Results

[0362] (1) Blood tests

[0363] Blood tests showed that 0% of participants had abnormal AST levels at baseline. 16% of participants had abnormal ALT levels. Compared to baseline, AST levels remained normal in 95% of participants. 5% of participants had elevated levels. For ALT levels, 6% of participants had improved levels. 89% of participants maintained normal levels. 5% of participants had higher levels.

[0364] (2) Fibroscan results

[0365] At baseline, 64% of participants had fatty liver. 50% of participants had fatty liver disease. After 3 months, compared to baseline, 70% of participants had improved liver fat levels. After 6 months, compared to baseline, 73% had improved liver fat levels. After 12 months, compared to baseline, 76% had improved liver fat levels.

[0366] Among those who had a fatty liver at baseline, 83% improved their liver fat levels. 43% had their liver fat levels return to a normal CAP score. Among those with fatty liver disease at baseline, 79% improved their liver fat levels. 45% no longer had fatty liver disease, and of those, 80% had their excessive liver fat levels return to a normal CAP score.

[0367] 3. Conclusion

[0368] The results of the study showed that consuming one bottle of the composition daily can reduce liver fat and treat fatty liver disease. These results suggest that daily consumption of one bottle of the composition may reduce the prevalence of non-alcoholic fatty liver disease.

[0369]

[0370] Example 4. Efficacy in non-alcoholic fatty liver disease

[0371] Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, affecting one in three adults. Severe NAFLD (cirrhosis) is currently the major indicant for liver transplantation in the United States.

[0372] The purpose of the study is to determine the effect of the composition on a mouse model of NAFLD.

[0373] A fat, fructose, and cholesterol-enriched liquid diet (FFC: 60E% carbohydrate, 25E% fat, 15E% protein, 50% fructose wt / wt, 0.16% cholesterol wt / wt; Ssniff, Germany) was used to induce NAFLD in C57BL / 6 mice. Male mice were randomly assigned to FFC or control groups (6-9 week period) (see FIG. 1). The composition was administered daily (added to the liquid diet) at 1.7 ml / mouse (equivalent to a human dose of 22 ml) according to a volume measurement method considering body surface area and differences in animal body weight. Evaluation variables were liver biochemistry (serum alanine aminotransferase, ALT, and aspartate aminotransferase, AST), serum high-density lipoprotein (HDL), and histologic liver fat quantification (fat proportional area, FPA).

[0374] (1) NAFLD prevention model

[0375] No changes in liver biochemistry were caused by treatment with the composition. There were no changes in liver biochemistry (FIG. 2). Quantification of liver fat showed a significant reduction in liver fat accumulation. Quantification of liver fat showed a significant reduction in liver fat accumulation compared to the FFC diet alone (FIG. 3). There was also a trend toward increased HDL in the group treated with the composition (FIG. 4).

[0376] (2) NAFLD treatment model

[0377] Similar to the NAFLD prevention model, adding the formulation at week 6 did not change liver biochemistry (data not shown). The FFC+DEL group showed a trend toward improved liver fat accumulation compared to the FFC-only group after the addition of the formulation at week 6. Additionally, the addition of the formulation at week 6 significantly improved HDL levels (FIG. 6).

[0378] While the foregoing has described in detail certain aspects of the present invention, it will be apparent to one of ordinary skill in the art that these specific descriptions are merely preferred examples and are not intended to limit the scope of the present invention. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims

1.A composition for the prevention or treatment of fatty liver, comprising:(1) dibenzo-p-dioxine derivatives; and(2) polyphenolic compounds.2.The composition according to claim 1, which further comprises 5 to 12% by dry weight of Polygonatum var., 10 to 20% by dry weight of Astragalus membranaceus Bge., 5 to 15% by dry weight of Artemisiae Scopariae Herba, 2 to 7% by dry weight of Puerariae Radix, 10 to 45% by dry weight of Codonopsis polisula NANNF, 10 to 20% by dry weight of White Hoelen, 5 to 20% by dry weight of Atractylodes macrocephala koidz, 5 to 15% by dry weight of Rehmanniae Radix, 2 to 10% by dry weight of Curcuma longa, and 2 to 10% by dry weight of Mentha arvensis.3.The composition according to claim 1, wherein the dibenzo-p-dioxin derivative comprises at least one of the compounds of Formulae 1 to 10:[Formula 1][Formula 2][Formula 3][Formula 4][Formula 5][Formula 6][Formula 7][Formula 8][Formula 9][Formula 10]wherein R is hydrogen, alkyl, alkenyl, phenyl, phenylalkyl, alkanoyl, hydroxyphenyl, dihydroxyphenyl, or acyl.4.The composition according to claim 3, wherein the dibenzo-p-dioxin derivative is included in an amount of 0.1 to 5% by weight based on the total weight of the composition.5.The composition according to claim 4, wherein the dibenzo-p-dioxin derivative includes the following compounds, based on their contents contained in the composition:(a) 0.1 to 6% by weight of the dibenzo-p-dioxin derivative of Formula 1;(b) 5 to 60% by weight of the dibenzo-p-dioxin derivative of Formula 2;(c) 1 to 30% by weight of dibenzo-p-dioxin derivative of Formula 3;(d) 0.5 to 80% by weight of dibenzo-p-dioxin derivative of Formula 4;(e) 0.1 to 10% by weight of a dibenzo-p-dioxin derivative of Formula 5;(f) 0.5 to 15% by weight of a dibenzo-p-dioxin derivative of Formula 6;(g) 0.1 to 5% by weight of a dibenzo-p-dioxin derivative of Formula 7;(h) 0.1 to 5% by weight of a dibenzo-p-dioxin derivative of Formula 8;(i) 0.1 to 10% by weight by weight of a dibenzo-p-dioxin derivative of Formula 9; and(j) 0.1 to 12% by weight of dibenzo-p-dioxin derivative of Formula 10.6.The composition according to claim 1, wherein the polyphenolic compound comprises a compound of Formula 11:[Formula 11]7.The composition according to claim 1, wherein the fatty liver comprises alcoholic or non-alcoholic fatty liver.8.A health functional food for the prevention or improvement of fatty liver, including:(1) dibenzo-p-dioxine derivatives; and(2) polyphenolic compounds.9.The health functional food according to claim 8, which further comprises 5 to 12% by dry weight of Polygonatum var., 10 to 20% by dry weight of Astragalus membranaceus Bge., 5 to 15% by dry weight of Artemisiae Scopariae Herba, 2 to 7% by dry weight of Puerariae Radix, 10 to 45% by dry weight of Codonopsis polisula NANNF, 10 to 20% by dry weight of White Hoelen, 5 to 20% by dry weight of Atractylodes macrocephala koidz, 5 to 15% by dry weight of Rehmanniae Radix, 2 to 10% by dry weight of Curcuma longa, and 2 to 10% by dry weight of Mentha arvensis10.The health functional food according to claim 8, wherein the dibenzo-p-dioxin derivative comprises at least one of the compounds of Formulae 1 to 10:[Formula 1][Formula 2][Formula 3][Formula 4][Formula 5][Formula 6][Formula 7][Formula 8][Formula 9][Formula 10]wherein R is hydrogen, alkyl, alkenyl, phenyl, phenylalkyl, alkanoyl, hydroxyphenyl, dihydroxyphenyl, or acyl.11.The health functional food according to claim 8, wherein the dibenzo-p-dioxin derivative is included in an amount of 0.1 to 5% by weight based on the total weight of the composition.12.The health functional food according to claim 11, wherein the dibenzo-p-dioxin derivative includes the following compounds, based on their contents contained in the composition:(a) 0.1 to 6% by weight of the dibenzo-p-dioxin derivative of Formula 1;(b) 5 to 60% by weight of the dibenzo-p-dioxin derivative of Formula 2;(c) 1 to 30% by weight of dibenzo-p-dioxin derivative of Formula 3;(d) 0.5 to 80% by weight of dibenzo-p-dioxin derivative of Formula 4;(e) 0.1 to 10% by weight of a dibenzo-p-dioxin derivative of Formula 5;(f) 0.5 to 15% by weight of a dibenzo-p-dioxin derivative of Formula 6;(g) 0.1 to 5% by weight of a dibenzo-p-dioxin derivative of Formula 7;(h) 0.1 to 5% by weight of a dibenzo-p-dioxin derivative of Formula 8;(i) 0.1 to 10% by weight by weight of a dibenzo-p-dioxin derivative of Formula 9; and(j) 0.1 to 12% by weight of dibenzo-p-dioxin derivative of Formula 10.13.The health functional food according to claim 8, wherein the polyphenolic compound comprises a compound of Formula 11:[Formula 11]14.The health functional food according to claim 8, wherein the fatty liver comprises alcoholic or non-alcoholic fatty liver.

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