JP4745989B2 - Liver tissue cholesterol improver - Google Patents

Description

The present invention relates to a liver tissue cholesterol improving agent , and more particularly to a liver tissue cholesterol improving agent containing crown granules as an active ingredient.

  In general, lifestyle-related diseases such as obesity, hypertension, hyperglycemia, and hyperlipidemia are known as diseases caused by lifestyle such as high calorie diet, drinking / smoking, lack of exercise, and stress. These lifestyle-related diseases are known as risk factors for arteriosclerosis, which is a cause of adult diseases such as myocardial infarction and cerebral infarction, and are a serious social problem. In general, a symptom that is accompanied by a plurality of types of lifestyle-related diseases among lifestyle-related diseases that are risk factors for arteriosclerosis is called metabolic syndrome. More specifically, in addition to the symptoms of central obesity such as visceral fat accumulation, this refers to a case where two or more symptoms among hypertension, hyperglycemia, hypertriglyceremia, and low HDL cholesterolemia are met. . The present condition is that these symptom have not been fundamentally cured except for improvement of eating habits and moderate exercise. People with metabolic syndrome are at a higher risk of developing myocardial infarction and cerebral infarction than healthy individuals, so there is an urgent need for the development of preventive and therapeutic agents for factors associated with metabolic syndrome such as hypertension and hyperglycemia. ing.

By the way, four types of medicinal herbs, safflower (pepper), peony, senkyu and tanjin, which have the action of “live-blooded” as a herbal medicine, and a cabbage (Kubushi) that has a spiritual action, and There is known a crown granule prepared by blending two kinds of herbs of mokko at a predetermined blending ratio. Conventionally, coronal granule has been applied to improve symptoms such as headache, stiff shoulders, dizziness, palpitation and the like of middle-aged persons or those with a tendency to hypertension by various active ingredients. Moreover, the effect | action which suppresses the aging of a cell and the complication of diabetes which are described in patent document 1, 2 is also known.
JP 2006-28155 A JP 2006-63076 A

  This invention was made by elucidating the novel pharmacological action that the crown granule composed of natural herbal ingredients has the action of improving the symptoms of metabolic syndrome, as a result of intensive studies by the present inventors. The object is to provide a metabolic syndrome ameliorating agent that is excellent in the action of improving the symptoms of metabolic syndrome.

In order to achieve the above object, the liver tissue cholesterol improving agent according to the first aspect of the present invention comprises 2.6 to 6.8 parts by weight of Dansang, 0.6 to 1.7 parts by weight of cabbage, 0.6 to 0.6 parts of wood incense. Effective crown granule containing 1.7 parts by weight, safflower 1.1-3.4 parts by weight, glaze 1.1-3.4 parts by weight, and nematode 1.1-3.4 parts by weight as constituent crude drugs Fatty liver caused by increased cholesterol in liver tissue due to metabolic syndrome with endogenous hypertriglyceridemia that occurs only as an increase in neutral fat synthesized in the liver as a component The method is characterized in that it is used for lowering increased cholesterol in liver tissue.

ADVANTAGE OF THE INVENTION According to this invention, the liver tissue cholesterol improving agent excellent in the effect | action which improves the symptom of metabolic syndrome can be provided.

Hereinafter, an embodiment of a metabolic syndrome ameliorating agent embodying the present invention will be described.
The metabolic syndrome ameliorating agent of this embodiment contains a crown granule as an active ingredient. Metabolic syndrome is a symptom associated with multiple types of lifestyle-related diseases. More specifically, the metabolic syndrome refers to a case where two or more symptoms among hypertension, hyperglycemia, hypertriglyceremia, and low HDL cholesterolemia are present in addition to symptoms of central obesity. In general, lifestyle-related diseases such as obesity, hypertension, hyperglycemia, and hyperlipidemia are known as diseases caused by lifestyle such as high calorie diet, drinking / smoking, lack of exercise, and stress. These lifestyle-related diseases are known as risk factors for arteriosclerosis, which is a cause of adult diseases such as heart disease. When arteriosclerosis progresses, for example, cardiovascular diseases such as myocardial infarction, angina pectoris, cerebral infarction, renal failure, and obstructive arteriosclerosis develop. Therefore, a patient corresponding to metabolic syndrome has a higher risk of developing a myocardial infarction, a cerebral infarction, or the like associated with arteriosclerosis than a healthy person. The metabolic syndrome ameliorating agent of the present embodiment exerts an improvement effect on lifestyle-related diseases that are factors associated with metabolic syndrome by the crown granule that is an active ingredient.

Central obesity, which is a definition of metabolic syndrome, means that fat accumulates in the center of the body, that is, the abdomen (internal organs), and is also referred to as visceral fat type obesity. It is possible to determine by abdominal CT imaging. As a simple judgment standard, when using a waist size (a waist circumference of the height of the navel), it indicates 85 cm or more for men and 90 cm or more for women. When using the waist / hip ratio, it means 0.9 or more for men and 0.85 or more for women. When BMI (body mass index: body weight (kg) / height (m) ² ) is used, it indicates 30 or more. Visceral fat type obesity is considered to be more related to arteriosclerosis than subcutaneous fat type obesity.

  The hypertension in the metabolic syndrome specifically refers to a case corresponding to at least one of a maximum blood pressure of 130 mmHg or more and a minimum blood pressure of 85 mmHg or more. When hypertensive symptoms occur, high pressure results in damage to the vascular endothelium and thickening of the vessel wall. Arteriosclerosis occurs as these symptoms progress. As arteriosclerosis worsens, a vicious cycle occurs in which hardened blood vessels further promote hypertension.

The hyperglycemia in metabolic syndrome indicates a case where the blood glucose level is 110 mg / dl or more on an empty stomach or the value of glycohemoglobin (glycated hemoglobin: HbA _1c ) exceeds 5.6. Glycohemoglobin is a sugar-binding dye in which hemoglobin is covalently bonded to glucose non-enzymatically in vivo. Since glucose binds to hemoglobin in erythrocytes when a hyperglycemic state continues for a long time, it has been conventionally used as one of the indicators of diabetes. The hyperglycemic state is accompanied by the generation of active oxygen and lipid peroxide and damages the vascular endothelium. Such vascular endothelium damage leads to atherosclerosis.

  Specifically, hypertriglyceremia in metabolic syndrome refers to a case where the concentration of neutral fat in blood is 150 mg / dl or more. Neutral fat is a fatty acid ester of glycerin, and representative one is triacylglycerol (triglyceride (TG)). TG in the blood is carried in a state of being incorporated into a lipoprotein core. Neutral fat is synthesized from fatty acids and sugars in the liver in the case of excess energy intake in addition to dietary intake. When it is synthesized excessively in the liver, it becomes fatty liver in which fat is excessively accumulated, and when triglyceride is further released from the liver, hypertriglyceridemia occurs. In the case of healthy individuals, the neutral fat in the blood usually shows the maximum value in about 4 hours and returns to the original value in about 12 hours. However, in the case of hypertriglyceridemia, the postprandial triglyceride value becomes abnormally high, and the recovery to pre-meal values is gentle over time. Hypertriglyceridemia is regarded as a risk factor for visceral fat obesity and arteriosclerosis.

  Specifically, low HDL cholesterolemia in metabolic syndrome refers to a case where the concentration of HDL cholesterol in blood is less than 40 mg / dl. HDL cholesterol is high-density lipoprotein cholesterol and is commonly called good cholesterol. HDL cholesterol has an anti-arteriosclerotic action because it has a role of returning excess cholesterol in each cell or blood vessel wall to the liver. Cholesterol returned to the liver is excreted as bile or reused as a hormone or LDL (low density lipoprotein). When the HDL cholesterol concentration is lowered, the balance with the LDL cholesterol (low density lipoprotein cholesterol) concentration that transports cholesterol to cells throughout the body is lost, and arteriosclerosis is promoted.

  The metabolic syndrome ameliorating agent of the present embodiment is preferably applied as an ameliorating agent for each symptom because the coronal granule, which is an active ingredient, exerts an ameliorating action on each symptom of the metabolic syndrome. Among these symptoms of metabolic syndrome, the coronal granule, which is an active ingredient, is particularly excellent in the action of improving hypertension, hyperglycemia, hypertriglyceridemia and low HDL cholesterolemia. Therefore, it is more preferably applied as a hypertension improving agent, a hyperglycemia improving agent, a hypertriglyceridemia improving agent and a low HDL cholesterolemia improving agent for patients with metabolic syndrome. Furthermore, since hypertension, hyperglycemia, hypertriglyceridemia, and low HDL cholesterolemia are considered as risk factors for arteriosclerosis, they should be preferably applied as an arteriosclerosis improving agent or an arteriosclerosis preventing agent. Can do.

  The crown granule, which is the active ingredient of this embodiment, has four types of herbs, safflower, peony, tankyu, and tanjin, which have the effect of “revitalize” as herbal ingredients, It is a Chinese herbal medicine (Chinese herbal medicine) prepared by blending two kinds of herbs, Kobushi (Kubushi) and Mika (Mokko), which have an action (improves feelings).

  This coronal granule was born in China in the 1960s from research on therapeutic agents for cerebrovascular and cardiovascular diseases. In 1969, Kannashin Ichigo consisted of 9 kinds of herbal medicines, followed by 5 kinds in 1978. Kannashin No. 2 consisting of herbal medicines (tansan, glaze, senkyu, safflower, and incense) was born, and the crown granule, in which incense was replaced with incense and incense, was approved as a pharmaceutical product in Japan in 1990. .

  The compounding ratio of each constituent crude drug contained in the crown granule is 2.6 to 6.8 parts by weight of Dansan, 0.6 to 1.7 parts by weight of Katsuki, 0.6 to 1.7 parts by weight of incense, and safflower. 1.1 to 3.4 parts by weight, 1.1 to 3.4 parts by weight of glaze, and 1.1 to 3.4 parts by weight of senkyu are preferable, and the weight ratio of Dansang, Katsuki, Mika, safflower, glaze and senkyu 4: 1: 1: 2: 2: 2 is more preferable. This coronal granule has been known to have the efficacy and effect of improving various symptoms such as headache, head weight, stiff shoulders, dizziness, palpitation, etc., although it has been in the middle age or higher than before.

  Dansang is the root of the Labiatae perennial tanjin (Salvia miltiorrhiza Bunge). Katsuki is the rhizome of the perennial grasshopper (Cyperus rotundus Linne) in the family Cyperaceae. Incense is the root of the perennial South Leapala (Auslandia lappa Decne (Saussurea lappa Clarke)) of the Compositae family. The safflower is a tubular flower of the plant safflower (Carthamus tinctorius Linne) of the Compositae 1-2 year. The glaze is the root of the perennial peony (Paeonia lactiflora Pallas) in the Paeoniaceae family. The nematode is a rhizome of the perennial sensu (Cnidium officinale Makino) of the Umbelliferae family.

  The crown granule is obtained by mixing the constituent crude drugs at a predetermined blending ratio and extracting the mixture with hot water using 5 to 30 times, preferably 10 to 20 times the amount of the total weight of the mixture. A granular product produced by concentrating and drying an aqueous extract (crown granule extract). The concentration and drying are performed by conventional means such as a vacuum evaporation concentration method, a spray drying method, a freeze drying method and the like. According to the production method of this crown granule, for example, Dansan 4.5 g, Katsuki 1.125 g, Kikko 1.125 g, Safflower 2.25 g, Glaze 2.25 g and Senkyu 2.25 g (total 13.5 g) From this, a crown granule extract having a solid content of 4.5 g is obtained. The crown granule produced in this way is used as a metabolic syndrome ameliorating agent in the present embodiment.

  The crown granule (solid matter) thus obtained may be taken as it is in the form of a powder or powder, or it may be used together with suitable excipients, bases, emulsifiers, solvents, stabilizers and other additives. , Tablets, capsules, pills, suppositories, solutions, injections, etc. may be processed and administered. Moreover, it is also possible to process and take in the form of a drink etc. based on the hot water extract before the said drying or its concentrate.

  The metabolic syndrome ameliorating agent is formulated so that the crown granule as an active ingredient is preferably administered in an amount of about 1 to 20 g, more preferably about 4.5 g per day for an adult, and the daily dose is multiple times a day (3 It is particularly preferred to be prescribed for taking between meals or on an empty stomach. The metabolic syndrome ameliorating agent containing the crown granule as an active ingredient can be used for use as a medicine or food by being contained in a medicine such as Chinese medicine or a food such as health food or general food.

According to the metabolic syndrome improving agent of the present embodiment, the following effects can be obtained.
(1) The metabolic syndrome ameliorating agent of the present embodiment contains a crown granule containing six kinds of herbal ingredients as an active ingredient. Therefore, the metabolic syndrome improving effect can be exhibited by ingestion.

  (2) The metabolic syndrome ameliorating agent of the present embodiment can effectively exert an improving action on hypertension, hyperglycemia, hypertriglyceremia, and low HDL cholesterolemia, particularly by the crown granule that is an active ingredient. it can. Therefore, it is expected that it can be suitably used for persons suffering from these diseases.

  (3) Hypertension, hyperglycemia, hypertriglyceridemia and low HDL cholesterolemia are considered risk factors for arteriosclerosis. Therefore, the metabolic syndrome improving agent of the present embodiment can be preferably applied as an arteriosclerosis improving agent or an arteriosclerosis preventing agent.

  (4) Further, since arteriosclerosis is a symptom caused by cardiovascular disease such as myocardial infarction, angina pectoris, cerebral infarction, renal failure, obstructive arteriosclerosis, etc., the metabolic syndrome improvement of this embodiment The agent can be applied as an ameliorating or preventing agent for those cardiovascular diseases.

(5) Since the metabolic syndrome ameliorating agent of this embodiment is based on a Chinese herbal medicine that is already widely used as a raw material, there is no worry about side effects.
(6) In addition, the crown granule blended as an active ingredient in the metabolic syndrome ameliorating agent of this embodiment has other medicinal properties (efficacy / effect to improve various symptoms such as headache, head weight, stiff shoulders, dizziness, palpitation, diabetes, etc. Therefore, their effects can be expected by ingestion.

Note that the metabolic syndrome ameliorating agent of the present embodiment can be modified and embodied as follows.
-The metabolic syndrome improving agent of this embodiment is preferably applied to the treatment of patients with metabolic syndrome. However, not only for therapeutic use, but also for healthy individuals to take for the prevention of metabolic syndrome.

  The metabolic syndrome ameliorating agent of this embodiment is administered to domestic animals (non-human mammals) such as horses, cows and pigs, poultry such as chickens, and pets such as dogs, cats, rats and mice, in addition to humans. May be.

  The crown granule, which is the active ingredient, may be contained in taste products such as bread, cakes and snacks, dairy products such as milk and yogurt, and beverages such as soft drinks.

Next, the embodiment will be described in more detail with reference to each test example.
(Preparation of crown granules)
The constituent crude drug of the crown granule used in this test and its content are: 2.25 g glaze, 2.25 g nematode, 2.25 g safflower, 1.125 g cabbage, 1.125 g wood incense and 4 It consists of .5g of Dansang. 20 times the amount of water was added to the mixture of these constituent crude drugs, and hot water extraction was performed at 100 ° C. for 1 hour. Then, after filtration, the filtrate was concentrated under reduced pressure to distill off the solvent, whereby a 44% yield of crown granule (crown granule extract) was obtained.

(Production and evaluation of high-fructose diet-fed rats)
As an evaluation model for metabolic syndrome, rats with a high fructose diet load have been used. Fructose (fructose) is usually used as an energy source in the body. However, when excessive intake is made in a high fructose diet, excess fructose is converted into glucose or converted into neutral fat (triglyceride) by gluconeogenesis in the liver. An increase in neutral fat (triglyceride) in the liver increases VLDL cholesterol (very low density lipoprotein cholesterol) and causes lifestyle-related diseases such as hyperlipidemia (hypertriglyceridemia).

８週齢のウイスター系雄性ラットを用い、高フルクトース食を与えることにより、高フルクトース食負荷ラットを作製した。まず、表１に示されるような各栄養成分を所定の配合比で混合させた高フルクトース食（フルクトース６５％）を作製した。次に、高フルクトース食をラットに一週間投与した。その後採血し、一群につき１１匹ずつ３群（コントロール群、第１群及び第２群）にグループ分けをした。なお、各群に属するラットはそれぞれ血清中トリグリセリド値及び体重が概ね揃うようにグループ分けされた。次いで、第１群及び第２群のモデルラットに対し、冠元顆粒をそれぞれ一日当たり５０ｍｇ／ｋｇ体重及び１００ｍｇ／ｋｇ体重の投与量となるように胃ゾンデで１４日間、連日経口投与した。なおこのとき、前記冠元顆粒は蒸留水に溶解した状態で経口投与された。一方、コントロール群（Control Rat）は冠元顆粒の代わりに蒸留水のみを与えた。連日経口投与終了後、血液及び肝臓を採取するとともに、下記評価項目について測定した。また、高フルクトース食の代わりに表１に示される正常食（Normal Diet）を投与したラットを正常ラット（Normal Rat）として比較のため同評価項目を測定した。

A high-fructose diet-fed rat was prepared by giving a high-fructose diet using 8-week-old male Wistar rats. First, a high fructose food (fructose 65%) was prepared by mixing each nutrient component as shown in Table 1 at a predetermined blending ratio. Next, a high fructose diet was administered to the rats for a week. Thereafter, blood was collected and divided into 3 groups (control group, first group and second group), 11 animals per group. The rats belonging to each group were divided into groups so that the serum triglyceride level and body weight were almost uniform. Subsequently, the coronal granule was orally administered daily for 14 days with a gastric sonde to the model rats of the first group and the second group so that the daily dose of the coronal granule was 50 mg / kg body weight and 100 mg / kg body weight, respectively. At this time, the crown granule was orally administered in a state dissolved in distilled water. On the other hand, the control group (Control Rat) gave only distilled water instead of the crown granule. After completion of oral administration every day, blood and liver were collected and the following evaluation items were measured. Moreover, the same evaluation item was measured for the comparison as the rat which administered the normal diet (Normal Diet) shown in Table 1 instead of the high fructose diet as a normal rat.

(Ratological measurement of rats, measurement of blood pressure and lipid content)
The body weight, liver weight, cardiac systolic blood pressure and diastolic blood pressure of the rats in each administration group were measured. Moreover, the total cholesterol concentration and triglyceride concentration of each rat group were measured using a known colorimetric method. The results are shown in Table 2. In addition, the amount of triglyceride and total cholesterol in the liver tissue of rats in each administration group were also measured in the same manner. The results are shown in FIG.

表２に示されるように、高フルクトース食によって肝重量が増加していることが確認される。また、表２及び図１に示されるように血清中の総コレステロール濃度及びトリグリセリド濃度、並びに肝組織中の総コレステロール量及びトリグリセリド量が増加していることが確認された。高フルクトース食によって、高中性脂肪血症を含む高脂血症、及び肝臓中に脂肪が蓄積する脂肪肝が発症しているものと思料される。一方、高フルクトース食に冠元顆粒を併せて投与したラット群において、これらの数値は、冠元顆粒の投与量依存的に減少していることが確認された。

As shown in Table 2, it is confirmed that the liver weight is increased by the high fructose diet. Further, as shown in Table 2 and FIG. 1, it was confirmed that the total cholesterol concentration and triglyceride concentration in serum and the total cholesterol amount and triglyceride amount in liver tissue were increased. The high fructose diet is thought to cause hyperlipidemia, including hypertriglyceridemia, and fatty liver in which fat accumulates in the liver. On the other hand, in the group of rats administered with the high fructose diet together with the crown granule, it was confirmed that these values decreased depending on the dose of the crown granule.

  Further, as shown in Table 2, it is confirmed that the systolic blood pressure value and the diastolic blood pressure value are increased by the high fructose diet. It is thought that hypertension is caused by a high fructose diet. On the other hand, in the group of rats administered with the high fructose diet together with the crown granule, it was confirmed that these values decreased depending on the dose of the crown granule.

(Measure blood glucose level)
Serum glucose concentration (blood glucose level) was measured using a known colorimetric method. In addition, the serum glycoprotein concentration was measured. Glycoprotein concentration is used as one index for determining a chronic hyperglycemic state because glucose binds to a protein in serum when the hyperglycemic state continues for a long time. Glycoprotein has an action of promoting arteriosclerosis. For example, in LDL cholesterol, LDL cholesterol composed of glycated protein is likely to be deposited on the vascular endothelium, and in HDL cholesterol, HDL cholesterol composed of glycated protein decreases the effect of carrying cholesterol to the liver.

  For the measurement of glycoprotein, first, serum was separated from the collected blood, then diluted 10-fold with distilled water, 0.75 mL of oxalic acid was added to 1 mL, and heated at 100 ° C. for 270 minutes. Thereafter, 40% trichloroacetic acid was added and mixed, followed by centrifugation at 3,000 rpm for 20 minutes. 0.25 mL of thiobarbituric acid was added to 1 mL of the supernatant after centrifugation, and after reacting at 37 ° C. for 30 minutes, the absorbance at 443 nm was measured and converted to the amount of glycated protein. The results are shown in Table 2.

  Further, as shown in Table 2, it is confirmed that the blood glucose level is increased by the high fructose diet. Moreover, it was confirmed that the glycoprotein concentration also increased. It is thought that hyperglycemia, which is a chronic hyperglycemia state, has developed due to a high fructose diet. On the other hand, in the group of rats administered with the high fructose diet together with the crown granule, it was confirmed that these values decreased depending on the dose of the crown granule. The crown granule is expected to suppress arteriosclerosis by suppressing an increase in glycoprotein concentration and suppressing a decrease in the action of lipoproteins such as LDL and HDL.

(Measurement of lipid peroxide amount)
The amount of lipid peroxide in serum and liver tissue was measured. Furthermore, in the liver tissue, the amount of lipid peroxide in the mitochondrial fraction where the generation of active oxygen was particularly remarkable in the cells was measured. Lipid peroxide is considered to cause cirrhosis such as arteriosclerosis and fatty liver. That is, an increase in the amount of lipid peroxide in the serum increases the onset of arteriosclerosis, and an increase in the amount of lipid peroxide in the liver tissue may increase the onset of fatty liver. In addition, it is known that patients with hypertension and hyperglycemia tend to increase the amount of lipid peroxide in the blood.

  A specific measurement method is as follows. First, 150 mL of a sample solution, 1.5 mL of 0.05N hydrochloric acid, and 0.5 mL of 0.67% thiobarbituric acid are reacted at 95 ° C. for 30 minutes, so that malon as an index of lipid peroxide amount A thiobarbituric acid reactant (TBA-RS) having a dialdehyde (MDA) structure was generated. After stopping the reaction, 2 mL of 15% methanol-containing butanol was added, and after centrifuging at 3,000 rpm for 10 minutes, the absorbance was measured at 535 nm. The results are shown in Table 3. It shows that there are many amounts of lipid peroxide, so that there are many amounts of TBA-RS.

表３に示されるように、高フルクトース食によって血清中及び肝組織（特に肝ミトコンドリア）中の過酸化脂質の量が著しく増加していることが確認される。一方、高フルクトース食に冠元顆粒を併せて投与したラット群において、これらの数値は、冠元顆粒の投与量依存的に減少していることが確認された。

As shown in Table 3, it is confirmed that the amount of lipid peroxide in serum and liver tissue (particularly liver mitochondria) is significantly increased by a high fructose diet. On the other hand, in the group of rats administered with the high fructose diet together with the crown granule, it was confirmed that these values decreased depending on the dose of the crown granule.

(Western blotting analysis of nuclear transcription factor SREBP-1)
The nuclear transcription factor SREBP-1 is known to regulate the expression of fatty acid metabolism-related gene information. Increased expression of the SREBP-1 gene indicates that fatty acid synthesis is activated. In this experiment, the expression of the nuclear transcription factor SREBP-1 in the liver tissue in each rat group was examined by Western blotting. First, using an extraction buffer (25 mM Tris-HCl (pH 7.5), 250 mM NaCl, 5 mM EDTA, 1% nonidet P-40, 1 mM phenylmethylsulfonyl fluoride (PMSF), 1 mM DTT, 50 μL protease inhibitor cocktail) from liver tissue. Extracted protein components in the tissue. In Western blotting, 30 μg of protein is dissolved in an electrophoresis buffer, subjected to SDS-PAGE by a conventional method, transferred to a nitrocellulose membrane, and the nitrocellulose membrane is subjected to immunoblot analysis (immunoblot). analysis). In this experiment, β-actin, which is a protein that is constantly expressed in almost all organs, was used as a standard marker for protein expression.

  In this immunoblot analysis, anti-SREBP-1 monoclonal antibody, anti-β-actin monoclonal antibody, and peroxidase-labeled secondary antibody were used. All of these antibodies were purchased from Santa Cruz Biotechnology Inc. The immunoblot analysis was performed by photographing the nitrocellulose membrane by the ECL (enhanced chemiluminescence) method. The results are shown in FIG.

  As shown in FIG. 2, it is confirmed that the amount of the nuclear transcription factor SREBP-1 is significantly increased by the high fructose diet. On the other hand, in the group of rats administered with the high fructose diet together with the crown granule, it was confirmed that these values decreased depending on the dose of the crown granule. It is thought that the expression level of SREBP-1 is decreased by the crown granule, and the synthesis of fatty acids related to SREBP-1 is decreased.

(Western blotting analysis of nuclear transcription factors NF-κB and COX-2)
Cyclooxygenase-2 (COX-2) is involved in the production of prostaglandin E2 involved in inflammation, and is a protein component that can cause many arteriosclerosis-related diseases. COX-2 gene expression occurs upon activation of the transcription factor NF-κB. Normally, NF-κB binds to I-κB in the cytoplasm and exists in an inactivated state. NF-κB, when dissociated from I-κB and activated, moves into the nucleus and promotes transcription of inflammation-related enzyme genes such as the COX-2 gene. Oxidative stress due to free radicals or the like is known to activate NF-κB of this transcription factor.

  In this experiment, the expression of nuclear transcription factors NF-κB and COX-2 in liver tissue in each rat group was examined by Western blotting. First, using an extraction buffer (25 mM Tris-HCl (pH 7.5), 250 mM NaCl, 5 mM EDTA, 1% nonidet P-40, 1 mM phenylmethylsulfonyl fluoride (PMSF), 1 mM DTT, 50 μL protease inhibitor cocktail) from liver tissue. Extracted protein components in the tissue. In Western blotting, 30 μg of protein is dissolved in an electrophoresis buffer, subjected to SDS-PAGE by a conventional method, transferred to a nitrocellulose membrane, and the nitrocellulose membrane is subjected to immunoblot analysis (immunoblot). analysis). In this experiment, β-actin, which is a protein that is constantly expressed in almost all organs, was used as a standard marker for protein expression.

  In this immunoblot analysis, anti-NF-κB monoclonal antibody, anti-COX-2 monoclonal antibody, anti-β-actin monoclonal antibody, and peroxidase-labeled secondary antibody were used. All of these antibodies were purchased from Santa Cruz Biotechnology Inc. The immunoblot analysis was performed by photographing the nitrocellulose membrane by the ECL (enhanced chemiluminescence) method. The results are shown in FIG.

  As shown in FIG. 3, it is confirmed that the amount of nuclear transcription factors NF-κB and COX-2 is increased by a high fructose diet. On the other hand, in the group of rats administered with the high fructose diet together with the crown granule, it was confirmed that these values decreased depending on the dose of the crown granule. In particular, it is confirmed that the expression level of the nuclear transcription factor NF-κB is decreased compared to normal mice.

  As described above, symptoms of hypertension, hyperglycemia, and hypertriglyceridemia, which are relevant factors of metabolic syndrome, were confirmed in rats with a high fructose diet. It was also confirmed that lipid peroxides related to arteriosclerosis and oxidative stress-related factors such as prostaglandin E2 synthesis-related protein COX-2 were increased. On the other hand, it was confirmed that in the high fructose diet-fed rats, the mice administered with the coronal granule improved their symptoms depending on the concentration of the coronal granule. It was confirmed that the coronal granule has an effect of improving or preventing arteriosclerosis as well as improving each symptom of metabolic syndrome.

Next, technical ideas that can be grasped from the above-described embodiment and other examples will be described below together with their effects.
(A) A method for administering a metabolic syndrome ameliorating agent, which is used as an agent for improving or preventing cardiovascular disease. Therefore, according to the invention described in (a), improvement or prevention of cardiovascular disorders associated with arteriosclerosis is expected due to the improvement or prevention of arteriosclerosis.

  (B) A pharmaceutical product or food or drink containing the metabolic syndrome ameliorating agent as an active ingredient. Therefore, according to the invention described in (b), the metabolic syndrome ameliorating agent can be taken efficiently.

  (C) A method for administering a metabolic syndrome ameliorating agent, wherein the active ingredient is administered at 50 to 100 mg / kg body weight / day. Therefore, according to the invention described in (a), the metabolic syndrome improving action can be effectively exhibited.

The graph which shows the influence by the crown granule of the lipid amount in a liver tissue. (A) A graph showing the amount of triglyceride in liver tissue. (B) A graph showing the amount of total cholesterol in liver tissue. The graph which shows the result of having quantified the photograph of the membrane at the time of investigating the expression of nuclear transcription factor SREBP-1 by Western blotting, and the expression level. The graph which shows the result of having quantified the photograph of the membrane at the time of investigating the expression of nuclear transcription factor NF- (kappa) B and COX-2 by western blotting, and the expression level. (A) A graph showing the expression level of nuclear transcription factor NF-κB. (B) A graph showing the expression level of COX-2.

Claims (1)

2.6-6.8 parts by weight of Dansan, 0.6-1.7 parts by weight of Katsuki, 0.6-1.7 parts by weight of incense, 1.1-3.4 parts by weight of safflower, 1.1 of glaze ~ 3.4 parts by weight, and 1.1 to 3.4 parts by weight of senkyu as a constituent crude drug, containing as the active ingredient, only due to an increase in neutral fat synthesized in the liver Improvement of liver tissue cholesterol used to lower the increased liver tissue cholesterol in fatty liver caused by increased cholesterol in liver tissue due to metabolic syndrome with onset of intrinsic hypertriglyceridemia Agent.

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