KR101791574B1 - Pharmaceutical composition for preventing or treating female menopausal disorder comprising an extract of black rice aleurone layer - Google Patents
Pharmaceutical composition for preventing or treating female menopausal disorder comprising an extract of black rice aleurone layer Download PDFInfo
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- KR101791574B1 KR101791574B1 KR1020150157772A KR20150157772A KR101791574B1 KR 101791574 B1 KR101791574 B1 KR 101791574B1 KR 1020150157772 A KR1020150157772 A KR 1020150157772A KR 20150157772 A KR20150157772 A KR 20150157772A KR 101791574 B1 KR101791574 B1 KR 101791574B1
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Abstract
The present invention relates to a pharmaceutical composition for the prevention and treatment of a female menopausal disorder comprising an extract of black rice aleurone layer as an active ingredient. More specifically, the present invention relates to a pharmaceutical composition for preventing and treating female menopausal disorder, In the ovariectomized rats, ovariectomized rats suppressed body weight gain, decreased body fat content, body fat index, liver lipid and triglyceride, decreased serum triglyceride, blood cholesterol and leptin levels, increased adiponectin concentration , Increases bone mineral content by increasing calcium content, decreases alkaline phosphatase (ALP) activity, increases serum estradiol content, and increases parathyroid hormone parathyroid hormone (PTH) in the blood, US hobuncheung extract may be useful in pharmaceutical compositions for the prevention and treatment of menopausal disorders.
Description
The present invention relates to a pharmaceutical composition for the prevention and treatment of a female menopausal disorder which contains, as an active ingredient, an extract of a black rice rind (aleurone layer).
Korea has entered an aging society since 2000 with the improvement of living and medical level. With the increase of life expectancy, interest in maintaining a healthy life in women after menopause is getting higher. Metabolic changes before and after menopause are associated with body fat distribution, lipid and various hormone metabolism, and increase the prevalence of vascular dysfunction, obesity, cardiovascular disease and osteoporosis. Estrogen deficiency associated with menopause leads to weight gain, especially abdominal fat, which increases the risk of metabolic syndrome and cardiovascular disease, increases blood lipid levels, and deposits lipids in the liver. Thus, estrogen replacement therapy (ERT) has been attempted to improve obesity and obesity-related complications in postmenopausal women, but with the reported occurrence of cancer in the reproductive organs, efforts to find solutions in natural foods without side effects continue .
In addition, osteoporosis due to osteoporosis is a problem in women who are progressing through menopause. Osteoporosis is a metabolic bone disease with a marked decrease in bone mineral density and bone strength compared with normal people due to decrease in bone constituents. The imbalance of absorption and osteogenesis, especially estrogen deficiency due to menopause, has become a major problem in menopausal women. Estrogen is involved in skeletal metabolism by synthesizing a substance that inhibits osteoclast activity by acting on osteoblast. Bone loss rate is accelerated after 5 to 10 years due to estrogen deficiency after menopause, and bone mineral density is gradually decreased by aging. The decrease in bone mass is due to individual differences or various other causes, but if the bone mass is excessively decreased due to pathological changes and falls below a predetermined value, fracture easily occurs even with a small impact. It is known that osteoporosis can not lead to a healthy life by restricting long-term activities due to various fractures, especially fractures of the femur, which are easily caused by weakening of the bone rather than the symptom itself, resulting in 15% of the deaths of the elderly have. A variety of drugs have been used in addition to endogenous regulators to treat or prevent osteoporosis induced by excessive osteoclast activity. However, these drugs are known to have various side effects and difficulties in taking medicines. Therefore, it is required to develop a new substance which has new action and drug structure, less toxicity and side effects, and is effective for prevention or treatment of osteoporosis. In addition, since these new substances are highly likely to be found in natural products that have not been used for a long time by folk remedies, attempts to create new drugs from natural products are being actively pursued.
Among the foods that are used for bone health in the private sector, black rice is cultivated and produced in Korea nationwide, and various products using black rice materials are being developed. Black rice anthocyanin is a water-soluble flavonoid-based natural pigment, which is also processed into various forms of food. It is attracted much attention as 'black food' because it is a natural food with a dark red color. In addition, phenolics are known to have various physiological functions because they have a hydroxyl group and have a binding property to macromolecules. Antioxidants (Sangkitikomol et al., Genet Mol. Res. 9: 2086-2095) H. et al., Plant foods Hum. Nutr. 62: 1-6), inflammation relief (Guo, H. et al., J. Nutr. Biochem. 23: 349-360), fatty liver improvement (Jang, H. et al., Nutr. Metab. 9: 27-38), arteriosclerosis prevention and treatment (Xia, X. et al., J. Nutr. 136: 2220-2225), enhancement of immune function (Wang, Q. et al., Asia Pac. 16: 295-301).
In this study, we found that aleurone layer from black rice, which is known to be effective in lipid metabolism and able to help bone health, was found in menopausal women In the model ovariectomized rats, the ovariectomized body weight gain was suppressed, and body fat content, body fat index, liver lipid and triglyceride were decreased, blood triglyceride, blood cholesterol and leptin levels were decreased but adiponectin concentration , Increase bone mineral content by increasing calcium content, decrease alkaline phosphatase (ALP) activity, increase serum estradiol content, increase parathyroid hormone (PTH) of the present invention, it is possible to reduce the concentration of parathyroid hormone Extract of the present invention has been completed by identifying that may be useful in the prevention or treatment a pharmaceutical composition of the menopausal disorders.
An object of the present invention is to provide a pharmaceutical composition and a health functional food for the prevention and treatment of a female menopausal disorder which contains an extract of a rice black rice aleurone layer as an active ingredient.
In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of a menopausal disease containing an extract of black rice aleurone layer as an active ingredient.
In addition, the present invention provides a health functional food for preventing or ameliorating a menopausal disease containing an extract of black rind fungus as an active ingredient.
In the present invention, the aleurone layer collected from black rice inhibits ovariectomized weight gain in ovariectomized rats, an animal model of postmenopausal women, and inhibits body fat content, body fat index, liver total lipid and triglyceride , Decreases serum triglyceride, blood cholesterol and leptin levels, increases the level of adiponectin, affects bone mineral density and development of the tibia, increases the calcium content and affects the bone mineral content. Alkaline phosphatase (alkaline phosphatase) phosphatase (ALP) activity, increased estradiol content in the blood, and decreased blood levels of parathyroid hormone (PTH), the black rhamnose extract of the present invention was found to prevent or treat menopausal diseases And can be usefully used as a pharmaceutical composition.
FIG. 1 is a graph showing the effect of black rice aleurone layer on weight gain of ovariectomized experimental animals.
Fig. 2 is a graph showing the effect of black rumen extract on the kidney circumference, abdomen and total fat weight of ovariectomized rats.
FIG. 3 is a graph showing the effect of black rumen extract on the obesity index of ovariectomized rats.
FIG. 4 is a graph showing the effect of black rumen extract on blood triglyceride and total cholesterol levels in ovariectomized rats.
FIG. 5 is a graph showing the effect of black rumen extract on the levels of adiponectin and leptin in ovariectomized rats.
FIG. 6 is a graph showing the effect of black rumen extract on total liver lipid, triglyceride and total cholesterol content.
FIG. 7 is a graph showing the effect of black rice extract on the adipocyte size of adipose tissue.
Fig. 8 is a graph showing the effect on the body weight of the experimental animals due to the black cohosh extract.
Fig. 9 is a graph showing the effect of the black rumen extract on the concentration of calcium present in the femoral region of ovariectomized rats.
FIG. 10 is a graph showing the effect of black rumen extract on the alkaline phosphatase activity of serum of ovariectomized rats.
FIG. 11 is a graph showing the effect of the black rumen extract on the osteocalcin level of serum of ovariectomized rats.
FIG. 12 is a graph showing the effect of black rumen extract on serum estradiol levels in ovariectomized rats.
FIG. 13 is a graph showing the effect of black rumen extract on the parathyroid hormone level of ovariectomized rats.
Hereinafter, the present invention will be described in detail.
The present invention provides a pharmaceutical composition for the prevention and treatment of a menopausal disease containing an extract of black rice aleurone layer as an active ingredient.
The extract is preferably extracted with water, a C 1 to C 2 lower alcohol or a mixture thereof, and the lower alcohol is preferably ethanol or methanol.
The menopausal disease may be selected from the group consisting of facial flushing, sweating, skin dryness, vaginal dryness, vaginal atrophy, lower urinary atrophy, vaginitis, cystitis, dysuria, Arthralgia, or osteoporosis, and it is most preferable that weight gain and osteoporosis are selected.
In a specific example of the present invention, the aleurone layer collected from black rice inhibits weight gain due to ovariectomy in ovariectomized rats, an animal model of postmenopausal women (see Fig. 1), and the body fat content, (Fig. 2 to Fig. 6), and the effect on the bone mineral density and development of the tibia is reduced by increasing the concentration of adiponectin (See Table 2), lower alkaline phosphatase (ALP) activity, increase serum estradiol content, increase parathyroid hormone (PTH) levels, (See Figs. 8 to 11).
Therefore, the black rumen extract may be useful as a pharmaceutical composition for the prevention or treatment of menopausal diseases.
The pharmaceutical composition may further comprise a pharmaceutically acceptable additive.
The additive may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.
The pharmaceutical dosage forms of the compositions of the present invention may also be used in the form of their pharmaceutically acceptable salts and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable set.
The pharmaceutical preparations containing the composition according to the present invention can be administered orally in the form of oral preparations such as tablets, pills, capsules, powders, suspensions, granules or expectorates, external preparations, suppositories and sterile injection solutions according to conventional methods And can be used as formulations. Examples of carriers, excipients and diluents that can be included in the pharmaceutical preparation containing the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As a suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.
The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
In addition, the present invention provides a health functional food for preventing or ameliorating a menopausal disease containing an extract of black rind fungus as an active ingredient.
The extract of the present invention inhibits weight gain due to menopausal diseases and confirmed that it has an influence on bone density and development of tibia, and thus it can be used as a health functional food for prevention or improvement of menopausal diseases.
As used herein, the term "health functional food" is produced by using raw materials or ingredients (functional raw materials) having functions useful for nutrients or human body that are likely to be deficient in daily eating, and is intended to maintain the normal function of the human body, But is not limited to, and is not meant to exclude health food in the usual sense.
The composition of the present invention can be added directly to food or used together with other food or food ingredients, and can be suitably used according to conventional methods. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (for prevention or improvement). In general, the amount of the compound in the health functional food may be 0.01 to 90 parts by weight based on the total weight of the food. However, when consumed for a long period of time for the purpose of health and hygiene or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.
The health functional beverage composition of the present invention is not particularly limited to the ingredients other than those containing the above-mentioned crunch angle as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. As a flavor other than the above, a natural flavoring agent {tau martin, stevia extract (for example, rebaudioside A, glycyrrhizin etc.)} and synthetic flavorings (saccharin, aspartame, etc.) have.
In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks.
These components may be used independently or in combination.
Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples.
However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.
< Example 1> Black rice The extract and Black rice Horn Anthocyanin content analysis of extracts
<1-1> Black rice Preparation of extract
Black rice was pulverized and extracted with 10 times (w / v) 50% ethanol at 40 ° C for 48 hours. The extract was filtered with a filter paper, concentrated, and lyophilized to use in the experiments of the present invention.
<1-2> Black rice Horn Preparation of extract
The aleurone layer of black rice was pulverized and extracted with 10
<1-3> Anthocyanin content analysis
The anthocyanin content of the black rice extract and black rumen extract of the black rice produced through Examples <1-1> and <1-2> were analyzed and are shown in Table 1 below.
For the analysis of anthocyanin content, 1 g of dry sample was placed in a 50 ml test tube, 20 ml of 5% formic acid solution was added, and the mixture was centrifuged (3000 rpm, 10 minutes) after extraction in a water bath at 40 ° C for 24 hours. The calculated values were calculated using the internal standard substance (
(mg / g)
(mg / g)
(mg / g)
As a result, the content of anthocyanin in black rumen extract was about 5 times higher than that of black rice extract (Table 1).
< Example 2> Production of animal models for menopausal disease and dietary regulation
Five-week-old Sprague-Dalwley female rats were divided into two groups: sham (Central Lab. Inc., Seoul, Korea) or ovariectomy (OVX) (Diets (D12451), New Brunswick, NJ, USA) with a fat content of 45% in the diet. Black rice extract (BRE) was orally administered at 30 mg or 90 mg per kg body weight for 12 weeks. Rats were individually housed and conditioned at 23 ± 1 ° C, 65 ± 5% RH and 12 hours / day, and water and experimental diet were fed free. Body weight was measured once a week, and dietary intake was measured three times a week. All laboratory animal procedures were approved by the National Institute of Agricultural Science and Technology (NAAS 1408).
< Example 3> Sampling
The rats were anesthetized with CO2 and blood was collected from the heart. The animals were anesthetized with distilled water and IF (soy isoflavone (10 mg / kg body weight) and BRE (30 mg or 90 mg / kg body weight) The blood was centrifuged at 3,000 rpm for 20 minutes to separate the plasma, and the liver and fat were collected from the blood, and weighed and rapidly frozen in liquid nitrogen. The adiposity index was calculated as follows .
Adiposity index = (total fat content / final weight) x 100
For statistical analysis of all results, the results were expressed as mean and standard error for each experimental group using SAS program (package version 9.2, Korea), and the effects of IF and BRE were analyzed by ANOVA, The difference between groups at the p <0.05 level was verified by Duncan's multiple range test.
< Experimental Example 1> Dietary intake and Identification of weight gain
The body weight gain after feeding the experimental diet and the black rumen extracts for 12 weeks is shown in Fig. Initial body weight at the beginning of the experiment and the dietary intake during the experimental period were not significantly different among all the experimental groups. However, the body weight gain calculated by the final body weight and the initial body weight was significantly increased in the OVX group compared to the Sham group. Supplementation of BRE and IF reduced the body weight gain of the ovariectomized experimental animals, Respectively. The weight of liver tissue was not significant, but it was lower in BRE group than in OVX and IF group. Thus, BRE was shown to be effective in inhibiting weight gain due to ovariectomy and a 12-week high fat diet (Fig. 1).
< Experimental Example 2> Confirmation of body fat content and body fat index
The body fat content and body fat index of the experimental animals were measured by the method of Example 3 above.
As a result, the kidney peripheral fat, visceral fat, total fat content, and body fat index of the experimental animals are shown in FIG. 2 and FIG. The fat content around the kidneys was increased in the OVX group but decreased in the BRE group and the visceral fat content was significantly increased in the OVX group as compared with the Sham group, but was significantly decreased by IF and BRE administration (Fig. 2 ).
The body fat index, which is the ratio of total fat content to body weight, was significantly increased by ovariectomy, but supplementation of IF and BRE increased body fat index (Fig. 3). This is interpreted as the effect of cyanidin-3-O-glucoside (C3G) and peonidin-3-Oglucoside (P3G)
< Experimental Example 3> Serum lipid, Adiponectin And Of leptin Confirm concentration
Serum triglyceride and total cholesterol were measured in the plasma using an enzyme kit (ASAN Diagnostics, Korea). Serum leptin and adiponectin were analyzed using a Rat kit (R & D system, Minneapolis, MN).
As a result, as shown in Figs. 4 and 5, blood triglyceride and total cholesterol concentrations of the experimental animals are shown in Fig. Supplementation of IF and BRE-90 significantly reduced serum triglyceride levels and, although not significant, showed a trend of lowering total cholesterol concentration in the BRE supplementation group (Fig. 4).
Adiponectin and leptin are hormones secreted from adipocytes, which regulate food intake and energy homeostasis. Adiponectin levels in normal obesity are lower than normal levels. However, in this study, , Which appears to compensate for increased body fat in ovariectomized laboratory animals and was significantly higher in the BRE group than in the OVX group (Figure 5).
In addition, serum leptin levels were significantly increased in the OVX group compared to the Sham group, but significantly decreased in the IF group and the BRE group (Fig. 5). In the obese model, the leptin concentration in the blood is increased to compensate for the decreased sensitivity to leptin, and the leptin concentration in the blood is known to be an index reflecting the degree of body fat.
In ovariectomized models, estrogen deficiency also affected blood lipid levels and related hormone levels in addition to body weight and body fat content, while black rice extracts were shown to modulate these changes.
< Experimental Example 4> Confirmation of liver total lipid, triglyceride and total cholesterol content
Total lipid in liver was measured by Bligh et al. (1959). Specifically, 0.5 g of liver was homogenized with 1.5 ml of 0.9% saline, 7.5 ml of a 2: 1 (v / v) mixed solution of chloroform and methanol was added, and the mixture was allowed to stand for 30 minutes or longer. Then, 2.5 mL of chloroform and 2.5 mL of distilled water were added and the mixture was centrifuged at 3,000 rpm for 20 minutes. The separated chloroform layer was applied to ADVANTEC paper (No. 6) (ADVANTEC Co., Tokyo, Japan) containing sodium sulfate ), Dried, and weighed.
The triglyceride and total cholesterol concentrations of the liver were determined by dissolving the total lipids extracted with 0.5% triton x-100 in ethanol and using an enzyme kit (Asanpharm, Korea) in the same manner as serum lipids.
As a result, as shown in Fig. 6, the liver total lipid and triglyceride of the experimental animals were significantly increased in all the OVX group as compared with the Sham group. Total lipid was decreased by 6-10% in IF group and black rice supplement group compared with OVX group, and especially, triglyceride was decreased by 20-22%. Total cholesterol in the liver did not differ between the experimental groups as in blood total cholesterol (Fig. 6).
< Experimental Example 5> Identification of fat cell size
In order to confirm the size of adipocytes, an adipose tissue was fixed in a 10% formalin solution and the H & E staining slides were prepared. The images were taken with an Olympus AX 70 camera. As shown in FIG. 7, when the lengths of the three longest axes of the largest fat cells in the cis field were obtained at different high magnifications (× 400), the results were lower in the IF group and the BRE group, (Fig. 7).
< Experimental Example 6> Black rice Horn Determination of the effect of extract on bone mineral density, bone mineral content and strength
Bone mineral density (BMD) was measured in the femur and tibia after administration of 90 mg / kg body weight of black rice extract (BRE) using the experimental animals of Example 2, And bone mineral content (BMC) were measured using an animal bone densitometer (
Calcium and phosphorus contents of the tibia were analyzed by the Food and Drug Testing Method. The tibia was dry-blended at 600oC in a furnace, decomposed in a nitric acid solution, and used as an analytical sample. The content of calcium was analyzed by atomic emission spectrometry (ICP-OES, Perkinelmer, USA) and the content of phosphorus was measured using a spectrophotometer (UV / VIS spectrophotometer, Mecasys, Korea) according to the molybdenum blue colorimetric method.
As a result, as shown in Table 2, the bone mineral density of the femur and tibia in the osteoporosis model was decreased by 5% to 6% in the osteoarthritic model, while the bone mineral density of the femur and tibia in the experimental group (OVX-BRE) And 2% and 8%, respectively, and tibia showed significant difference from OVX group. Bone mineral content (BMC) tended to decrease in ovariectomized animal models. BRE fed tended to increase 3% and 18% in femur and tibia, respectively, but there was a significant difference between the experimental groups (Table 2). Especially, ovariectomy significantly decreased calcium content of tibia, but it increased to near level of Sham group when BRE was fed. However, the phosphorus content of tibia did not show any significant difference between all experimental groups. Therefore, it was confirmed that BRE supplementation could affect bone mineral content by increasing calcium content in tibia.
In addition, the strength of bones was significantly higher in the OVX group (24% and 11%, respectively) than in the Sham group (p <0.05) and higher than in the Sham group (Table 2). Therefore, it is expected that the extract of black rumen may help prevent fractures which frequently occur in postmenopausal women.
Therefore, the supply of BRE seems to affect bone mineral density, bone mineral content and development of tibia rather than femoral bone.
The values are mean ± SEM (n = 8); Different letters on the same line are significantly different according to Duncan's multiple range test; NS: Not significantly different.
< Experimental Example 7> Identification of activity of biochemical indicators of blood
In order to confirm the activity change of the biochemical indicator according to the administration of the black rice extract, black rice extract (BRE) was administered to the experimental animals of Example 2 at a dose of 90 mg per kg of body weight, and then the following experiment was conducted .
Specifically, the blood was collected from the heart after being anesthetized with carbon dioxide gas (CO 2 ), and the serum was left at room temperature for 30 minutes and then centrifuged at 3,000 rpm for 20 minutes to use for the analysis of calcium metabolism and related hormone secretion . Biochemical parameters such as alkaline phosphatase (ALP) activity in the blood (Asan Pharmaceutical, Korea), parathyroid hormone (PTH ELISA Kit, USCN life science, China), osteoclacin (Osteocalcin ELISA kit, Biomedical technologies Inc., USA) and estradiol ELISA kit, Biovision., USA).
As a result, as shown in FIG. 8 to FIG. 11, the effect of the black rumen extract on serum ALP activity was higher in the OVX group than in the Sham group not ovariectomized, but the OVX -BRE group had a significantly decreased ALP activity (p < 0.05) than the OVX group (Fig. 8). In the BRE-treated group, the ALP activity was lower than in the OVX-treated group, whereas the BRE-treated group showed a lower bone ALP activity than the OVX-treated group Seems to be due to the stable state.
In addition, osteocalcin (OC) is synthesized in osteoblasts and deposited in the intracellular matrix of bone, and newly synthesized part is secreted into the blood, so it is used as mineral metabolism indicator of bone. In particular, serum OC concentration is increased after menopause and is known to be a good predictor of bone loss after menopause. In the present invention, the blood OC concentration of the OVX group was significantly higher than that of the Sham group, but the BRE administration did not show any effect (FIG. 9), indicating that the plant extracts affected other biochemical indicators but did not affect OC (2005). The results of this study are consistent with the results of this study.
In addition, the serum estradiol content used as a diagnostic index for osteoporosis was 45% lower in the OVX group than in the Sham group, but the OVX-BRE fed with BRE was 23% higher than that in the OVX group (FIG. 10) .
In addition, parathyroid hormone (PTH) is controlled by the calcium concentration in the blood secretion, low calcium levels increase the secretion of this hormone in the parathyroid glands. In the present invention, the blood PTH concentration of the OVX group was increased compared with the Sham group, but the blood PTH level was significantly decreased by the addition of the black rice extract (BRE), and there was no significant difference with the Sham group (FIG. 11).
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