Composition having effect of preventing or treating liver cell fat accumulation, comprising benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio]) as active ingredient

Abstract

The present invention relates to a pharmaceutical composition that effectively inhibits fat accumulation in liver cells at a concentration at which cytotoxicity does not occur, the composition comprising benzothiazole, 2-[[4-(trifluoromethyl) phenyl]thio] or a pharmaceutically acceptable salt thereof as an active ingredient.

Description

A composition having a preventive or therapeutic effect on hepatocyte fat accumulation, comprising benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] as an active ingredient

[0001] The present invention relates to a pharmaceutical composition for preventing or treating fat accumulation in liver cells, comprising benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof.

[0002] Fatty liver disease (FAD) is a condition caused by excessive fat accumulation in the liver. Fat, particularly triglycerides, constitutes more than 5% of the liver's weight. It is known to be caused by excessive alcohol consumption, drug use, hepatitis viruses, certain genetic disorders, and metabolic diseases such as obesity and type 2 diabetes.

[0003] Among these, alcohol-related fatty liver disease is classified as alcoholic fatty liver disease, and other types of fatty liver disease are classified as non-alcoholic fatty liver disease. It is a disease that starts from simple steatosis and progresses to steatohepatitis and liver cirrhosis.

[0004] There is no specific treatment for fatty liver disease other than lifestyle changes such as diet and exercise, and antidiabetic drugs (thiazolidinediones, metformin, GLP-1 agonist, DPP4 inhibitor), antioxidants and hepatoprotectors (vitamin E, ursodeoxycholic acid), and nonsteroidal anti-inflammatory drugs (NSAIDs) are used in a limited manner.

[0005] Currently, the development of fatty liver / steatohepatitis treatments using various new molecular targets is actively underway, including Elafibranor, a PPARα / δ ligand, Cenicriviroc, a CCR2 / 5 inhibitor, Obeticholic acid, an FXR agonist, and Selonsertib, an ASK-1 inhibitor, which are in phase 3 clinical trials. (Nature Medicine, 2018, 24:908-922)

[0006] Meanwhile, benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] has been reported to have anticancer effects by inhibiting sugar metabolism in cancer cells (Sci Rep, 2020, 16;10(1)).

[0007] However, there has not been much research on benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio], to date, and in particular, no research has been conducted on its effect in suppressing fat accumulation in liver cells.

[0008] The present invention is intended to solve the above-mentioned problem, and its purpose is to provide a pharmaceutical composition for preventing or treating fat accumulation in liver cells, characterized by comprising benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] and a pharmaceutically acceptable salt thereof.

[0009] The problems to be solved by the present invention are not limited to the problem(s) mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the description below.

[0010] In order to achieve the above-mentioned purpose, the present invention provides a pharmaceutical composition for preventing or treating fat accumulation in liver cells, comprising benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof as an active ingredient.

[0011] The present invention also provides a method for inhibiting fat accumulation in liver cells, comprising administering to a subject benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof.

[0012] In addition, the present invention provides a food composition for preventing or improving fat accumulation in liver cells, comprising benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

[0013] In addition, the present invention provides a feed composition for preventing or improving fat accumulation in liver cells, characterized in that it comprises benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

[0014] In addition, the present invention provides a cosmetic composition for preventing or improving fat accumulation in liver cells, characterized in that it comprises benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

[0015] According to the present invention, benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] can effectively suppress fat accumulation in hepatocytes at a low concentration that does not show cytotoxicity, and therefore can be widely used in the fields of medicine, food, cosmetics, and feed for preventing, improving, or treating fatty liver disease.

[0016] The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the detailed description of the present invention or the composition of the invention described in the claims.

[0017] Figure 1 shows the experimental results of Experimental Example 1. Figure 1 (A) shows the survival rate of mouse hepatocytes treated with palmitic acid (PA) and cultured for 24 hours, as confirmed by MTT assay, and Figure 1 (B) shows the survival rate confirmed by phase contrast microscopy.

[0018] Figure 2 is a diagram showing the experimental results of Experimental Example 2. Figure 2 (B) shows images of intracellular fat accumulation after treating mouse hepatocytes with palmitic acid at various concentrations and culturing them for 24 hours, using BODIPY 493 / 503 staining, and photographing them with a fluorescence microscope. Figure 2 (A) shows the numerical representation of these images.

[0019] Figure 3 is a diagram showing the experimental results of Experimental Example 3. Figure 3 (A) shows the cytotoxicity of hepatocytes treated with benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] at various concentrations, as confirmed by MTT assay, Figure 3 (B) shows the accumulation of intracellular fat after treating with benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] at various concentrations under a concentration of 50 μM palmitic acid, as stained with BODIPY 493 / 503, and Figure 3 (C) shows the quantification of the accumulation of intracellular fat.

[0020] Unless otherwise defined herein, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs.

[0021] Terms defined in commonly used dictionaries should be interpreted as having meanings consistent with their meanings in the context of the relevant technology, and should not be interpreted in an idealized or overly formal sense unless explicitly defined herein. Furthermore, when describing the present invention, detailed descriptions of related known technologies will be omitted if they are deemed to unnecessarily obscure the gist of the present invention.

[0022] Additionally, when a part of the present invention is said to "include" a certain component, this does not mean that other components are excluded, but rather that other components may be included, unless specifically stated otherwise.

[0023] The present invention provides a pharmaceutical composition for preventing or treating fat accumulation in liver cells, characterized in that it comprises benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] (BTPT) or a pharmaceutically acceptable salt thereof as an active ingredient.

[0024] The above benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] may be a compound represented by the following chemical formula 1. In addition, in the present invention, benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] may include various derivatives thereof, but the scope of the present invention is not limited thereto. In the present invention, benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] and derivatives thereof may all be compounds isolated from nature, chemically synthesized compounds, or commercially sold compounds.

[0025] [Chemical Formula 1]

[0026]

[0027] The above benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio], has been reported to have anticancer effects by inhibiting the sugar metabolism of cancer cells. However, to date, there has not been much research on the physiological activity of benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio], and in particular, no research has been conducted on its effect of inhibiting fat accumulation in liver cells.

[0028] In the present invention, it was confirmed that benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] effectively suppresses fat accumulation in normal hepatocytes within a range that does not exhibit intracellular toxicity, and thus, it is intended to apply the composition for preventing or treating fat accumulation in hepatocytes containing benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] as an active ingredient.

[0029] In the present invention, “pharmaceutically acceptable salt” means any organic or inorganic addition salt of benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] at a concentration that is relatively non-toxic and harmless to the individual receiving it and has an effective effect, and side effects caused by the salt do not reduce the beneficial effects of benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

[0030] The term "prevention" used in the present invention means any action that inhibits fat accumulation in hepatocytes by administering the composition of the present invention, or thereby delays the progression of fat accumulation in hepatocytes.

[0031] The term "improvement" or "treatment" as used in the present invention means any act of inhibiting fat accumulation in hepatocytes by administering the composition of the present invention, or thereby improving or beneficially changing the state of fat accumulation in hepatocytes, and means an attempt to obtain useful results or desirable results, including clinical results.

[0032] The pharmaceutical composition of the present invention can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods. Carriers, excipients, and diluents that can be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. When formulated, it is prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants that are commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and these solid preparations are prepared by mixing the compound of the present invention with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include witepsol, macrogol, Tween 61, cocoa butter, laurin, and glycerogelatin.

[0033] In addition to the above-mentioned effective ingredients, the above pharmaceutical composition may further include any compound or natural extract known to have already proven stability and activity in order to increase and enhance the effect of inhibiting fat accumulation in liver cells.

[0034]

[0035] According to one embodiment of the present invention, the fat accumulation may be induced by free fatty acids. The free fatty acids are also called non-ester fatty acids, and their main components include palmitic acid, stearic acid, oleic acid, etc., and can be transported to liver tissue by binding to albumin in the blood. If the function of adipocytes is abnormal due to causes such as an unbalanced diet and obesity, free fatty acids may be abnormally accumulated in liver tissue through lipolysis, which may increase the incidence and risk of fatty liver disease. Preferably, the fat accumulation may be induced by palmitic acid, but is not limited thereto.

[0036] The above fatty liver disease may include alcoholic fatty liver disease or non-alcoholic fatty liver disease.

[0037] The above fatty liver disease refers to a disease induced by fatty liver, and the fatty liver refers to a phenomenon in which neutral fat appears to be abnormally deposited within liver cells, unlike in normal cases. In a normal liver, approximately 5% is composed of adipose tissue, and neutral fat, fatty acids, phospholipids, cholesterol, and cholesterol esters are the main components of fat. However, once fatty liver occurs, most of the components are replaced by neutral fat, and if the amount of neutral fat exceeds 5% of the liver weight, it is diagnosed as fatty liver. The above fatty liver is caused by a disorder of fat metabolism within liver cells or a defect in the process of transporting excess fat.

[0038] The above alcoholic fatty liver disease refers to a case in which fat synthesis is promoted in the liver and normal energy metabolism is not carried out due to excessive alcohol consumption. Alcohol is not stored in the body and is completely eliminated through oxidation in the liver. Specifically, alcohol in the liver is metabolized by three major pathways: alcohol dehydrogenase (ADH) pathway, microsomal ethanol oxidizing system (MEOS) pathway, and catalase pathway, and is converted into acetaldehyde, which is then metabolized into acetate by aldehyde dehydrogenase (ALDH). At this time, the acetaldehyde is toxic and can damage liver cells, and in the microsomal alcohol oxidation pathway, reactive oxygen species (ROS) such as superoxide (O2), hydrogen peroxide (H2O2), and peroxynitrite are generated in the process of alcohol metabolism by activation of cytochrome P450-2E1 (CYP2E1; cytochrome P450 2E1), which causes oxidative stress and liver damage. In addition, as a result of the metabolism of alcohol, a large amount of fatty acids are produced, which causes fat to accumulate in the liver, and fatty liver accumulated in the liver due to this cause is called alcoholic fatty liver.

[0039] The above non-alcoholic fatty liver disease refers to cases in which fatty liver disease is present without a history of alcohol consumption, and is known to be related to metabolic diseases such as obesity, diabetes, and hyperlipidemia.

[0040] The above non-alcoholic fatty liver disease may include one or more selected from the group consisting of non-alcoholic simple fatty liver disease, non-alcoholic steatohepatitis, non-alcoholic cirrhosis, and end-stage fibrosing liver disease.

[0041] Nonalcoholic steatohepatitis (NSHE) refers to patients with nonalcoholic fatty liver disease (NAFLD) who develop severe or more severe inflammation. If treatment is delayed, it can progress to cirrhosis or hepatocellular carcinoma.

[0042] Nonalcoholic cirrhosis, also known as cirrhosis, refers to any form of liver disease characterized by significant hepatocyte loss, proliferation of fibrous tissue, and regenerative nodules. Cirrhosis can also be induced by insulin resistance, and complications such as ascites (fluid accumulation in the abdomen), variceal bleeding, and hepatic encephalopathy can occur.

[0043]

[0044] According to one embodiment of the present invention, the concentration of the benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof may be, but is not limited to, 10 to 50 μM. When the concentration of the benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof included in the pharmaceutical composition satisfies the above-mentioned range, not only is the effect of inhibiting fat accumulation in hepatocytes further improved, but there is also an advantage of excellent stability, such as no or very low cytotoxicity to hepatocytes. When the concentration of the benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof is less than the above-mentioned range, the effect of inhibiting accumulation in hepatocytes may be reduced, and when it exceeds the above-mentioned range, there is a problem that cytotoxicity may be enhanced.

[0045]

[0046] The present invention provides a method for inhibiting fat accumulation in hepatocytes, characterized by comprising the step of contacting liver cells in which fat accumulation is induced in vitro or ex vivo with a pharmaceutical composition containing benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof as an active ingredient.

[0047] In addition, the present method provides a method for inhibiting fat accumulation in hepatocytes, characterized in that it comprises a step of administering to a subject a pharmaceutical composition comprising the benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof as an active ingredient.

[0048] The term "subject" used in the present invention means any animal, including humans, in which fat accumulation in liver cells has occurred or can occur, and for example, the subject may mean a dog, cow, horse, rabbit, mouse, rat, chicken, or all mammals, including humans, but is not limited thereto, and the subject may be an individual other than a human.

[0049] The method of administering the above pharmaceutical composition to a subject is not particularly limited in the present invention, but may be administered by routes such as oral, rectal, intravenous, intramuscular, subcutaneous, intrauterine, or intracerebrovascular injection.

[0050] The dosage of the pharmaceutical composition may vary depending on the age, sex, and weight of the subject to be treated, the specific disease or pathological condition to be treated, the severity of the disease or pathological condition, the route of administration, and the prescriber's judgment, and is not particularly limited in the present invention. Determination of the dosage based on these factors is within the level of those skilled in the art, and may range from 0.01 mg / kg / day to about 2000 mg / kg / day, for example, and preferably from 0.1 mg / kg / day to 1000 mg / kg / day. The administration may be administered once a day or divided into several times, but this is not particularly limited in the present invention.

[0051]

[0052] Another aspect of the present invention relates to a food composition capable of preventing or improving fat accumulation in liver cells by effectively inhibiting fat accumulation in liver cells at a low concentration that does not exhibit cytotoxicity by including the aforementioned benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

[0053] The above food composition can be manufactured in all food forms, such as, for example, functional food, nutritional supplement, health food, food additive, etc., and the various forms of food can be manufactured in various ways according to conventional methods known in the art, and the present invention does not specifically limit this.

[0054] For example, the health food may be prepared by manufacturing the food composition itself in the form of tea, juice, or drink for consumption, or may be granulated, encapsulated, or powdered for consumption. In addition, the functional food may be prepared by adding a separate extract to beverages (including alcoholic beverages), fruits or processed foods thereof (e.g., canned fruits, bottled fruits, jams, marmalades, etc.), fish, meats or processed foods thereof (e.g., ham, sausages, corned beef, etc.), breads or noodles (e.g., udon, buckwheat noodles, ramen, spaghetti, macaroni, etc.), fruit juices, various drinks, cookies, taffy, dairy products (e.g., butter, cheese, etc.), edible vegetable oils, margarine, vegetable proteins, retort foods, frozen foods, various seasonings (e.g., soybean paste, soy sauce, sauces, etc.). In addition, the food composition of the present invention may be prepared in the form of a powder or concentrate for use as a food additive.

[0055] In order to be manufactured into various forms of food as described above, the food composition may further include, in addition to the above-mentioned effective ingredients, a food-relatedly acceptable carrier or additive, and, in the manufacture of the formulation or form to be manufactured, any carrier or additive known to be usable in the art may be further included without any special limitation.

[0056]

[0057] Another aspect of the present invention relates to a feed composition capable of preventing or improving fat accumulation in hepatocytes at a low concentration without cytotoxicity by including benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

[0058] The feed composition may include, but is not limited to, plant-based feeds such as grains, roots, food processing by-products, algae, fibers, pharmaceutical by-products, oils, starches, meal, or grain by-products; animal-based feeds such as proteins, minerals, oils, minerals, single-cell proteins, zooplankton, or food, and the like. The feed composition may refer to feeds commonly used in the art without any particular limitation.

[0059] The form of the above feed composition may include, but is not limited to, powdered feed, solid feed, moist pellet feed, dry pellet feed, EP (extruder pellet) feed, raw feed, etc.

[0060] The above feed composition may further include a binder, an emulsifier, a preservative, etc. in addition to the above-mentioned effective ingredients for the purpose of preventing quality deterioration, etc., and may further include additives such as amino acids, vitamins, enzymes, flavoring agents, non-protein nitrogen compounds, silicates, buffers, extractants, oligosaccharides, and feed mixers for the purpose of increasing utility, but is not limited thereto.

[0061]

[0062] Another aspect of the present invention relates to a cosmetic composition capable of preventing or improving fat accumulation in liver cells even at a low concentration that does not exhibit cytotoxicity by including benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

[0063] The formulation of the above cosmetic composition is not particularly limited in the present invention, but may be formulated as cosmetics such as, for example, a softening toner, an astringent toner, a nourishing toner, a nourishing cream, a massage cream, an essence, an eye cream, an eye essence, a cleansing cream, a cleansing foam, a cleansing water, a pack, a powder, a body lotion, a body cream, a body oil, or a body essence, and may be applied in a form that is applied to the skin or in a form that is absorbed into the skin using microneedles or the like.

[0064] The above cosmetic composition comprises, as a carrier acceptable in a cosmetic process, hydrocarbons such as petrolatum, liquid paraffin, and gelling hydrocarbon (nickname: plastibase); animal or vegetable oils such as medium-chain fatty acid triglycerides, lard, hard fat, and cacao fat; higher fatty acid alcohols and fatty acids and esters thereof such as cetanol, stearyl alcohol, stearic acid, and isopropyl palmitate; water-soluble bases such as macrogol (polyethylene glycol), 1,3-butylene glycol, glycerol, gelatin, sucrose, and sugar alcohols; emulsifiers such as glycerin fatty acid esters, polyoxyl stearate, and polyoxyethylene hydrogenated castor oil; adhesives such as acrylic acid esters and sodium alginate; propellants such as liquefied petroleum gas and carbon dioxide; It may further include preservatives such as paraoxybenzoic acid esters, and in addition to these, it may further include stabilizers, fragrances, colorants, pH adjusters, diluents, surfactants, preservatives, antioxidants, etc. as needed.

[0065] The above cosmetic composition, including the aforementioned components, may be prepared in the form of an external preparation using conventional methods. The external preparation may be applied to a local wound using conventional methods.

[0066]

[0067] Hereinafter, the contents of the present invention will be described in more detail with reference to the following experimental examples. However, the scope of the present invention is not limited to the following experimental examples, but includes modifications of technical ideas equivalent thereto.

[0068]

[0069] [Experimental Example 1: Confirmation of hepatocyte toxicity caused by palmitic acid]

[0070] Palmitic acid (PA) bound to bovine serum albumin (BSA) was treated at various concentrations (10, 20, 50, 100, 200, 500 μM) to mouse hepatocytes (AML12) and cultured for 24 hours. The cell viability was observed using an MTT assay (see (A) of Figure 1) and a phase contrast microscope (see (B) of Figure 1).

[0071]

[0072] Referring to FIG. 1 of the present invention, it can be confirmed that palmitic acid does not exhibit any significant cytotoxicity to hepatocytes up to 100 μM, but exhibits significant cytotoxicity at concentrations higher than that. ***p< 0.001 (vs control, palmitic acid concentration 0 μM).

[0073]

[0074] [Experimental Example 2: Confirmation of Fat Accumulation in Liver Cells by Palmitic Acid]

[0075] Palmitic acid bound to BSA was treated at various concentrations (20, 50, 100 μM) in AML12 mouse hepatocytes and cultured for 24 hours. After staining for intracellular lipid accumulation using BODIPY 493 / 503, the degree of lipid accumulation by palmitic acid was photographed using a fluorescence microscope (see (B) in Fig. 2) and quantified (see (A) in Fig. 2). In addition, the number of living cells was confirmed after staining the cell nucleus using Hoechest 33342 (see (B) in Fig. 2).

[0076]

[0077] Referring to FIG. 2 of the present invention, it was shown that fat accumulation increased in a concentration-dependent manner by treating hepatocytes with palmitic acid, and thus in vitro experimental conditions for fat accumulation in hepatocytes using palmitic acid were established.

[0078]

[0079] [Experimental Example 3: Inhibitory Effect of Benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] on Cytotoxicity and Hepatocyte Fat Accumulation]

[0080] Benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] was treated at various concentrations (5, 10, 50 μM) to mouse hepatocytes AML12, cultured for 24 hours, and then cytotoxicity was confirmed using the MTT assay (see (A) of Figure 3).

[0081] In addition, under experimental conditions in which fat accumulates in mouse hepatocytes AML12 (palmitic acid 50 μM), benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] was treated at various concentrations (10, 50 μM), and after 24 hours, the fat accumulation was stained with BODIPY 493 / 503 (see (B) of Figure 3) and its intensity was quantified and displayed (see (C) of Figure 3).

[0082]

[0083] Referring to (A) of FIG. 3 of the present invention, benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] was shown to have more than 80% of cells surviving up to a concentration of 50 μM, confirming that benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] does not exhibit cytotoxicity.

[0084] Referring to (B) of FIG. 3 of the present invention, it was confirmed that benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio], effectively inhibits fat accumulation caused by palmitic acid within a concentration that does not exhibit significant toxicity to hepatocytes.

Claims

1. A pharmaceutical composition for preventing and treating fat accumulation in hepatocytes, characterized in that it comprises benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] and an acceptable salt thereof as an active ingredient.

2. In paragraph 1, A pharmaceutical composition, characterized in that the above fat accumulation is induced by free fatty acids.

3. In paragraph 2, A pharmaceutical composition, characterized in that the free fatty acid is at least one of palmitic acid, stearic acid, and oleic acid.

4. In paragraph 1, A pharmaceutical composition, characterized in that the concentration of the benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof is 10 to 50 μM.

5. A method for inhibiting fat accumulation in hepatocytes, characterized by comprising a step of administering to a subject benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio] or a pharmaceutically acceptable salt thereof.

6. A food composition for preventing or improving fat accumulation in liver cells, characterized by containing benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

7. A feed composition for preventing or improving fat accumulation in liver cells, characterized by containing benzothiazole, 2-[[4-(trifluoromethyl)phenyl]thio].

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