KR101783309B1 - A composition comprising extract of Tradescantia spathacea Sw. or compounds isolated therefrom for preventing or treating metabolic disorder - Google Patents

Abstract

The present invention relates to a composition for the prophylaxis or treatment of a metabolic disease comprising an extract of purple persimmon or a compound isolated therefrom. The purple starch extract or the compound isolated therefrom is excellent in the inhibitory effect of protein tyrosine dehydrogenase 1B and can be usefully used as a composition for the prevention or treatment of metabolic diseases.

Description

FIELD OF THE INVENTION The present invention relates to a composition for preventing or treating metabolic diseases, which comprises extracts of purple flowers or compounds isolated therefrom. or compounds isolated therefrom for or treating metabolic disorder < RTI ID = 0.0 >

The present invention relates to a composition for the prevention or treatment of metabolic diseases, which comprises extracts of Tradescantia spathacea Sw. Or compounds isolated therefrom.

In spite of the great progress of modern life science, the recent trends of dietary habits due to economic development, aging of population and various stresses are increasing the incidence of cardiovascular and metabolic diseases including cancer. Particularly, among the above metabolic diseases, diabetes is a chronic wasting disease characterized by an abnormal glucose metabolism due to an absolute deficiency or resistance of insulin, and is a disease that causes various complications such as systemic weakness and resistance, vascular disorder, cerebral infarction, myocardial infarction (Danaei, G. et al., 2011).

Diabetes mellitus is classified into two types according to the cause of illness and the condition of the disease. Type 1 diabetes, a type of insulin-dependent diabetes mellitus that occurs due to the destruction of the beta cells of Langerhans islet due to a specific human lymphocyte antigen (HLA) and viral infection, and the genetic (family history of about 20%) and environmental This type of insulin-independent diabetes mellitus is caused by an increase in resistance to insulin in peripheral tissues such as muscle, liver, and adipose tissue. In particular, type 2 diabetes accounts for more than 90% of diabetic patients and the number of diabetic patients is steadily increasing due to changes in lifestyle such as aging and lack of exercise, obesity, overeating, drug abuse and stress in modern society Hossain, P. et al., 2007; Day, C., 2001).

Diabetes mellitus is caused by a variety of pathogenic mechanisms. Therefore, the treatment methods are also inevitably diverse. Moreover, there are many cases in which conventional therapeutic methods do not have satisfactory effects. In addition, studies on diabetes mellitus have been conducted mainly on type 2 diabetes drugs, which account for more than 90% of diabetic patients. Some of them are currently on the market, but many of them are still in the experimental stage, It is in inspection stage. In particular, rapid - acting insulin secretagogues and insulin resistance modifiers considering biorhythm will be one of effective methods for the treatment of diabetes, and it is expected that this drug opening will be more active in the future. In the past decade, research has been carried out on the cause of diabetes mellitus, presumably due to the insulin resistance caused by insulin receptor problems. Recently, however, research has been shifted toward the insulin signaling system.

The insulin signaling pathway inhibits the regulation of protein tyrosine phosphatase 1B (PTP1B), particularly among protein tyrosine dephosphorylases (Xue, B. et al., 2007). The protein tyrosine dephosphorylase 1B is known as an enzyme that induces insulin resistance by interfering with the signal transduction mechanism of insulin by causing dephosphorylation of insulin receptor and insulin receptor substrates. In addition, protein tyrosine dephosphorylase is also known to cause obesity by inhibiting leptin signal transduction and inhibiting phosphorylation of leptin receptor and Jak in leptin signal transduction (Malamas, M. S. et al., 2000).

Although studies on protein tyrosine dephosphorylase 1B to date have remained at a relatively early stage, recently, the biological function and pathogenesis mechanism of protein tyrosine dephosphorylase 1B has been clarified and it has become a target of new drug development (Thareja, S. et al., 2012). Particularly, since the role of protein tyrosine dephosphorylase 1B in the intractable diseases such as diabetes, obesity and cancer has been clarified, much investment has been made in the development of new drugs targeting the inhibition of this enzyme. As an example of this, it has been reported that insulin resistance is eliminated in rats in which protein tyrosine phosphatase 1B (PTP1B) gene has been removed, and obesity is inhibited without inducing type 2 diabetes (Elchebly, M. et al. et al., 1999). In addition, substances that inhibit protein tyrosine phosphatase 1B (PTP1B) have been shown to exhibit anti-diabetic effects (Klaman, L. D. et al., 2000).

The inhibitor of various tyrosine dephosphorylases including the protein tyrosine dephosphorylase 1B which has entered into clinical practice to date is shown in Reference 1 below. In many cases, it has been omitted from the clinical trials due to low bioavailability, toxicity and side effects. Thus, it has been reported that various naturally occurring compounds inhibit protein tyrosine dephosphorylase 1B (Coman, C. et al., 2002) 2012; Jiang, CS et al., 2012).

[Reference Figure 1]

Purple Early Years ( Tradescantia spathacea Sw.) has been traditionally used as a medicinal plant in Vietnam to alleviate coughing and bleeding symptoms (Do, TL, 2004), epigallocatechin, rutin, peltatoside (Tan, J. et al., 2013). (Gonzalez-Avila M. et al., 2003; Tan, J. et al., 2013), the antioxidant activity, antioxidant activity, and antimicrobial activity (Rosales-Reyes T. et al. Is disclosed.

Korean Patent Laid-Open Publication No. 2013-0136653 discloses a tea containing frequently roasted chicken roots and a method for manufacturing the same. Korean Patent No. 192835 discloses that the roasted chicken extract has a hypoglycemic effect. However, in the purple roots of the present invention, There is no previous report confirming the therapeutic effect of obesity or diabetes mellitus extract of the present invention or a compound isolated therefrom as another plant.

Korean Patent Laid-Open No. 2013-0136653, tea containing frequently roasted chicken, and a method of producing the tea, registered on December 13, 2013. Korean Registered Patent No. 192835, Chicken Chrysanthemum morifolium extract having a hypoglycemic effect, registered on Jan. 30, 1999.

Coman, C. et al., Plants and natural compounds with antidiabetic action, Not. Bot. Horti. Agrobo., 40 (1), 314-325, 2012. Cui, L. et al., Protein tyrosine phosphatase 1B inhibitors from Morus root bark, Bioorg. Med. Chem. Lett., 16 (5), 1426-1429, 2006. Danaei, G. et al., National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health surveys and epidemiological studies with 370 country-years and 2.7 million participants, Lancet, 378 9785), 31-40, 2011. Day, C., The rising tide of type 2 diabetes, Br. J. Diabetes. Vasc. Dis., 1 (1), 37-43, 2001. Do, T. L., Medicinal plants and drugs from Viet Nam (in Vietnamese), Medical Publishing House (Hanoi, Viet Nam), 2004. Elchebly, M. et al., Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene, Science, 283 (5407), 1544-1548, 1999. Gonzalez-Avila M. et al., Antigenotoxic, antimutagenic and ROS scavenging activities of a Rhoeo discolor ethanolic crude extract, Toxicol. in Vitro, 17 (1), 77-83, 2003. Hossain, P. et al., Obesity and diabetes in the developing world-a growing challenge, Engl. J. Med., 356 (3), 213-215, 2007. Jiang, C. S. et al., Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity in the last decades, Acta. Pharmacol. Sin., 33 (10), 1217-1245, 2012. Johnson, T. O. et al., Protein tyrosine phosphatase 1B inhibitors for diabetes, Nat. Rev. Drug. Discov., 1 (9), 696-709, 2002. Klaman, L. D. et al., Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice, Mol. Cell. Biol., 20 (15), 5479-5489, 2000. Malamas, M. S. et al., New azolidinediones as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties, J. Med. Chem., 43 (5), 995-1010,2000. Rosales-Reyes T. et al., Aqueous crude extract of Rhoeo discolor, a Mexican medicinal plant, and the formation of liver preneoplastic foci in rats, J. Ethnopharmacol., 115 (3), 381-386, 2008. Tan, J. et al., Antioxidant and antibacterial activity of Rhoeo spathacea (Swartz) Stearn leaves, J. Food Sci. Technol., 1-7, 2013. Thareja, S. et al., Protein tyrosine phosphatase 1B inhibitors: a molecular level legitimate approach for the management of diabetes mellitus, Med. Res. Rev., 32 (3), 459-517, 2012. Xue, B. et al., Protein tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance, J. Biol. Chem., 282 (33), 23829-23840, 2007.

It is an object of the present invention to provide a composition for the prevention or treatment of metabolic diseases, which comprises an extract of purple persimmon or a compound isolated therefrom.

The present invention relates to a process for producing spathacea Sw.) extract or a compound isolated therefrom. The present invention also relates to a composition for preventing or treating metabolic diseases. More specifically, the following formula 1 (2 R, 3 R) -2,3- dihydroxy-2-methyl-butyrolactone (Compound 1), Brac Te surprised Id A (Compound 2), 4- (3 ' , 4'-dihydroxyphenyl) furan -2 (5H) - source (compound 3), (S) -2- hydroxy-3- (4'-hydroxyphenyl) propionic acid (compound 4), (R) (Compound 5), Latipolysinin C (Compound 6), Latipolysinin B (Compound 7), Latipolysinin A (Compound 8), and 1, 2-hydroxy-3- (4'-hydroxyphenyl) propionic acid (Compound 9), Oresbuchin A (Compound 10), (±) -tradeascantin (Compound 11), (6 S, 9 R) - (. Tradescantia spathacea Sw) Reggio side (compound 12) and the trade's Kanto side early only purple comprising at least one compound selected from the group consisting of (compound 13) in that it contains an extract And to a composition for preventing or treating metabolic diseases.

[Chemical Formula 1]

The Purple Bay Early Seed Extract is characterized in that it is an extract obtained by extracting purple starch with at least one solvent selected from the group consisting of water, C1 to C4 lower alcohols, dichloromethane, ethyl acetate and n-butanol.

In addition, the present invention is the above formula (1) separated from the beginning of only purple (Tradescantia spathacea Sw.) (2 R, 3 R) -2,3- dihydroxy-2-methylbutyronitrile as the lactone (compound 1), Te Brac (3), ( S ) -2-hydroxy-3- (4'-dihydroxyphenyl) furan- Hydroxyphenyl) propionic acid (Compound 4), ( R ) -2-hydroxy-3- (4'-hydroxyphenyl) propionic acid (Compound 5), Latipolysinin C (Compound 6), Latipolysinin B 7), Latipolysinin A (Compound 8), 1- (3 ', 4'-dihydroxyphenyl) -2-hydroxyethan-1-one (Compound 9), Oresbuchin A (Compound 10) , (±) - comprises at least one compound selected from the group consisting of Reggio side (compound 12) and the trade's Kanto side (compound 13) - the trade's kantin (compound 11), (6 S, 9 R) And to a composition for preventing or treating metabolic diseases.

The metabolic disease may be a disease selected from obesity or diabetes.

In addition, the present invention of the formula 1 (2 R, 3 R) -2,3- dihydroxy-2-methylbutyronitrile as the lactone (compound 1), Brac Te surprised Id A (Compound 2), 4- (3 ', 4'-dihydroxyphenyl) furan -2 (5H) - source (compound 3), (S) -2- hydroxy-3- (4'-hydroxyphenyl) propionic acid (compound 4), (R ), 2-hydroxy-3- (4'-hydroxyphenyl) propionic acid (Compound 5), Latipolysinin C (Compound 6) (Compound 9), Oresbuchin A (Compound 10), (±) -tradeascantin (Compound 11) , (6 S, 9 R) - Reggio side (compound 12) and the trade's Kanto side (compound 13) containing the beginning of only purple containing at least one compound selected from the group extract consisting of (Tradescantia spathacea Sw.) And a health functional food for preventing or ameliorating a metabolic disease.

In another aspect, the present invention provides a method for purifying a purple early berry extract, comprising extracting a purple berry early stage with water, C1 to C4 lower alcohol or a mixed solvent thereof to prepare a purple early berry extract; Sequentially fractionating the purple bass early extract using dichloromethane, ethyl acetate and n-butanol; And of (2 R, 3 R) -2,3- dihydroxy-2-methylbutyronitrile as the lactone (compound 1), Brac Te surprised Id A (Compound 2) The formula (1) and the each fraction using chromatography (Compound 3), ( S ) -2-hydroxy-3- (4'-hydroxyphenyl) propionic acid (Compound 4), ( R ) -2-hydroxy-3- (4'-hydroxyphenyl) propionic acid (Compound 5), Latipolysinin C (Compound 6), Latipolysinin B (Compound 8), 1- (3 ', 4'-dihydroxyphenyl) -2-hydroxyethan-1-one (Compound 9), Oresbuchin A (Compound 10) kantin (compound 11), (6 S, 9 R) - , to a method for separating at least one compound selected from the group consisting of Reggio side (compound 12), and trade Kanto's side (compound 13).

The present invention also provides a novel compound (±) -tradescantantine (Compound 11) and tradeascantoide (Compound 13) of Formula 1 above.

Hereinafter, the present invention will be described in detail.

The present invention relates to a composition for the prevention or treatment of metabolic diseases, which comprises an extract of Tradescantia spathacea Sw. Or at least one compound selected from the group of compounds of formula (1) isolated therefrom.

The purple bark extract may be obtained by extracting water, a lower alcohol of C1 to C4 or a mixed solvent thereof in a purple color early stage. Examples of the lower alcohol of C1 to C4 include methanol, ethanol, propanol, isopropanol, Can be used. In addition, the purple bark extract may be a fraction obtained by fractionation with an organic solvent, and examples of the organic solvent include dichloromethane, ethyl acetate and n-butanol.

In addition, the compound isolated from the purple primrose of the present invention can be obtained by successively fractionating the purple early berry extract with dichloromethane, ethyl acetate and n-butanol to obtain respective fractions, and then fractionating the fractions by chromatography .

The chromatography was performed by silica gel column chromatography, flash column chromatography, sephadex LH-20 column chromatography, RP-18 column chromatography (RP -18 column chromatography, thin layer chromatography (TLC), medium pressure liquid chromatography and high performance liquid chromatography (HPLC).

Meanwhile, the compound of the present invention can be synthesized according to a conventional method in the art, and can also be prepared as a pharmaceutically acceptable salt.

The present invention also provides a pharmaceutical composition for the prevention or treatment of metabolic diseases comprising an extract of Purple Bay bark extract or at least one compound selected from the group of compounds of formula (1) isolated therefrom. The pharmaceutical composition containing the extract or the compound may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions, Can be used. Examples of carriers, excipients and diluents that can be contained in the pharmaceutical 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. Examples of suppository bases include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like.

The dosage of the pharmaceutical composition comprising the purple early berry extract of the present invention or the compound isolated therefrom may vary depending on the age, sex, body weight, the specific disease or condition to be treated, the severity of the disease or condition, It will depend on the judgment of the person. Dosage determinations based on these factors are within the level of ordinary skill in the art and generally the dosage ranges from 0.01 mg / kg / day to approximately 2000 mg / kg / day. A more preferable dosage is 1 mg / kg / day to 500 mg / kg / day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

The pharmaceutical composition comprising the purple early berry extract of the present invention or a compound isolated therefrom can be administered to mammals such as rats, 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 dural or intracerebral injection. Since the extract of the present invention or the compound isolated therefrom has little toxicity and side effects, it can be safely used even for long-term administration for preventive purposes.

The present invention also provides a method of preventing or ameliorating a metabolic disease such as diabetes or obesity, which comprises an extract of Purple Bass Juniperia or one or more compounds selected from the group of compounds of Formula 1 isolated therefrom and a pharmaceutically acceptable food supplementary additive And a health functional food. The extract or the compound may be added to the health functional food of the present invention in an amount of 0.001 to 100% by weight. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids. Examples of the foods to which the extract or compound of the present invention can be added include various foods, beverages, gums, tea, Vitamin complexes and the like.

The present invention relates to a composition for the prophylaxis or treatment of a metabolic disease comprising an extract of purple persimmon or a compound isolated therefrom. The purple starch extract or the compound isolated therefrom is excellent in the inhibitory effect of protein tyrosine dehydrogenase 1B and can be usefully used as a composition for the prevention or treatment of metabolic diseases.

1 is a graph showing the correlation (arrows) between ¹ H- ¹ H COZY (bold lines) and ¹ H- ¹³ C key HMBC on (±) -tradeascanthin (Compound 11) .
FIG. 2 is a graph showing the correlation (arrows) between ¹ H- ¹ H COZY (bold lines) and ¹ H- ¹³ C key HMBC for the novel compound of the present invention, trade susantoide (Compound 13).
FIG. 3 is a graph showing the correlation (arrow) of ¹ H- ¹ H key NOESY on the novel compound of the present invention, tradescantide (Compound 13). FIG.

Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, the intention is to provide an exhaustive, complete, and complete disclosure of the principles of the invention to those skilled in the art.

≪ Example 1: Isolation of purple starling compound >

The ground part of the Purple Early Bird ( Tradescantia spathacea Sw.) Used in the present invention was collected in October 2012 in Hue city. The above dried and pulverized purple starch (7 kg) was repeated three times with methanol (10 L) at 60 ° C for 3 hours to obtain an extract, which was concentrated under reduced pressure to obtain 750 g of a methanol extract. The methanol extract was suspended in 1.5 L of water and successively fractionated with dichloromethane (1 L × 6), ethyl acetate (1 L × 5), and n-butanol (1 L × 5), and the dichloromethane fraction (300 g) Ethyl acetate fraction (40 g) and n-butanol fraction (60 g) and finally fraction (250 g) containing water layer residue were obtained.

In addition, the inhibition effect on protein tyrosine dephosphorylase 1B was relatively high, and the ethyl acetate fraction and the n-butanol fraction, which had a comparatively high TLC pattern, were combined. The combined fractions (100 g) were subjected to open flash column chromatography (column size: 10 x 23 cm, silica gel: 230 - 300 cm) according to a gradient elution gradient of dichloromethane: methanol (50: 1 -> 0: 1 [v: v] 400 mesh) to obtain seven small fractions (TD1-TD7). TD2 was purified by silica gel column chromatography (column size: 6.0.times.15 cm, particle size: 40 .mu.m) according to the gradient elution gradient of n-hexane: ethyl acetate (9: 1 to 4: 1 [v: v] Compound (8) (75 mg) and four small fractions (TD2.1-TD2. The small fraction, TD2.2, was further purified by RP-18 column chromatography (column size: 2.0 x 15 cm, particle size: 40-40 cm) using a mobile phase of methanol: water (1:10 → 0: 1 [v: v] 63 [mu] m).

The small fraction, TD3, was purified by silica gel column chromatography (column size: 4.0 x 15 cm, particle size: 40-63 탆) according to concentration gradient elution conditions of n-hexane: acetone (4: ) To obtain three small fractions (TD3.1-TD3.2). Among these fractions, TD3.1 was fractionated by Sephadex LH-20 open column chromatography (column size: 2.0 × 50 cm, particle size: 25-100 μm) according to iso-solvent conditions of 100% 1 g). The small fraction, TD3.2, was further purified by high performance liquid chromatography (RP-18 column, manufactured by Tosoh Corporation) according to the concentration gradient elution condition of aqueous methanol solution (21% → 25% [v / v]) containing 0.1% [v / Compound 3 (5 mg), Compound 9 (9 mg), Compound 10 (70 mg) and Compound 11 (7 mg) were fractionated by column chromatography (column size: 250 x 20 mm ID, particle size:

The small fraction TD4 was purified by medium pressure liquid chromatography (column size: 5.0.times.20 cm, particle size: 40-63 .mu.m) according to concentration gradient elution with dichloromethane: methanol (40: 1 → 0: 1 [v: v] (TD4.1-TD4.4) was obtained. TD4.2 of the above-mentioned small fractions was purified by Sephadex LH-20 open column chromatography (column size: 2.0 x 50 cm, particle size: 25 -100 占 퐉) and RP-18 column chromatography (column size: 3.0 占 15 cm, particle size: 40-63 占 퐉) in accordance with concentration gradient elution method of methanol: water (1:10 → 0: 1 [v: v] Mu m) to separate Compound 2 (100 mg).

The small fraction, TD6, was purified by RP-18 column chromatography (column size: 3.0 占 15 cm, particle size: 40-63 占 퐉 according to concentration gradient elution conditions of methanol: water (1:10 → 0: 1 [v: v] ) To obtain four small fractions (TD6.1-TD6.4). TD6.1 was purified by silica gel column chromatography (column size: 3.0 × 15 cm, particle size: 40) according to the gradient elution method of dichloromethane: methanol (5: 1 → 0: 1 [v: v] (24 mg) and Compound 5 (23 mg) were fractionated with Sephadex LH-20 column chromatography (column size: 2.0 x 50 cm, particle size: 25-100 탆) of 100% Respectively. Further, the small fraction TD6.2 was fractionated by Sephadex LH-20 open column chromatography (column size: 2.0 x 50 cm, particle size: 25-100 탆) of 100% methanol, and then 0.1% [v / v] formic acid (RP-18 column, column size: 250 x 20 mm ID, particle size: 5 mu m) according to a concentration gradient elution condition of methanol aqueous solution (32% → 35% [v / v] And purified to obtain Compound 12 (10 mg). The TD6.4 fraction was purified by column chromatography on Sephadex LH-20 (column size: 2.0 x 50 cm, particle size: 25-100 탆) and dichloromethane: methanol (5: 1 → 0: 1 [v : v]) by silica gel column chromatography (column size: 3.0 × 15 cm, particle size: 40-63 μm) to obtain Compound 13 (8 mg).

Example 2. Confirmation of the physicochemical structure of the compound isolated from Purple Haze

Example 2-1. (2 R , 3 R ) -2,3-dihydroxy-2-methylbutyrolactone (Compound 1)

(2 R, 3 R) -2,3 -dihydroxy-2-methylbutyrolactone;

colorless oil;

MW: 132.11;

-57.8 ( c 0.4, MeOH);

_{^{1 H NMR (methanol- d 4,}} 600 ㎒) δ: 4.49 (1H, dd, J = 4.2, 10.2 ㎐, H-4a), 4.20 (1H, dd, J = 1.8, 10.2 ㎐, H-4b), 4.10 (1H, dd, J = 3.6, 1.2 Hz, H-2), 1.44 (3H, s, H-5);

_{^{13 C NMR (methanol- d 4,}} 150 ㎒) δ: 180.5 (C-1); 74.7 (C-2), 74.5 (C-3), 73.5 (C-4), 21.6 (C-5);

EI-MS m / z 132 [M] ^< ⁺ & gt ^; .

Example 2-2. Blacta theanolid A (compound 2)

bracteanolidea;

white amorphous powder;

MW: 208.17;

mp: 240-242 [deg.] C;

_{^{1 H NMR (methanol- d 4,}} 600 ㎒) δ: 7.25 (1H, d, J = 2.4 ㎐, H-2 '), 7.23 (1H, dd, J = 2.4, 8.4 ㎐, H-6'), 6.87 (1H, d, J = 8.4 Hz, H-5 '), 6.49 (1H, s, H-5), 6.28 (1H, s, H-3);

_{^{13 C NMR (methanol- d 4,}} 150 ㎒) δ: 174.3 (C-2); (C-4 '), 146.9 (C-3'), 122.8 (C-1 '), 122.5 (C-6'), 116.7 -2 '), 112.0 (C-3), 100.1 (C-5);

EI-MS m / z 208 [M] ^< ⁺ & gt ^; .

Examples 2-3. 4- (3 ', 4'-dihydroxyphenyl) furan-2 (5H) -one (Compound 3)

4- (3 ', 4'-dihydroxyphenyl) furan-2 (5H) -one;

amorphous powder;

MW: 192.17;

_{^{1 H NMR (methanol- d 4,}} 250 ㎒) δ: 7.11 (1H, s, H-2 '), 7.09 (1H, d, J = 6.3 ㎐, H-6'), 6.91 (1H, d, J = 6.3 Hz, H-5 '), 6.29 (1H, s, H-3), 5.33 (2H, s, H-5);

_{^{13 C NMR (methanol- d 4,}} 62.5 ㎒) δ: 177.7 (C-2), 167.9 (C-4), 150.9 (C-4 '), 147.2 (C-3'), 122.9 (C-1 ' ), 120.9 (C-6 '), 116.8 (C-5'), 114.8 (C-2 '), 109.8 (C-3), 73.1 (C-5).

Examples 2-4. ( S ) -2-hydroxy-3- (4'-hydroxyphenyl) propionic acid (Compound 4)

( S ) -2-hydroxy-3- (4'-hydroxyphenyl) propanoic acid;

white needles;

MW: 182.18;

-10.6 ( c 1.2, MeOH);

_{^{1 H NMR (methanol- d 4,}} 250 ㎒) δ: 6.96 (2H, d, J = 8.5 ㎐, H-3 ', H-5'), 6.58 (2H, d, J = 8.5, H-2 ' , H-6 '), 4.15 (1H, dd, J = 4.5, 7.5 ㎐, H-2), 2.89 (1H, dd, J = 4.0, 13.8 ㎐, H-3a), 2.69 (1H, dd, J = 7.8, 13.8 Hz, H-3b);

_{^{13 C NMR (methanol- d 4,}} 62.5 ㎒) δ: 177.5 (C-1), 157.2 (C-4 '), 131.7 (C-3', C-5 '), 129.7 (C-1'), 116.2 (C-2 ', C-6'), 73.2 (C-2), 40.9 (C-3).

Examples 2-5. ( R ) -2-hydroxy-3- (4'-hydroxyphenyl) propionic acid (Compound 5)

( R ) -2-hydroxy-3- (4'-hydroxyphenyl) propanoic acid;

white amorphous powder;

MW: 182.18;

+15.6 ( c 0.6, MeOH);

_{^{1 H NMR (methanol- d 4,}} 250 ㎒) δ: 7.00 (2H, d, J = 8.3 ㎐, H-3 ', H-5'), 6.58 (2H, d, J = 8.5, H-2 ' , H-6 '), 3.97 (1H, dd, J = 3.5, 8.3 ㎐, H-2), 2.91 (1H, dd, J = 3.5, 14.0 ㎐, H-3a), 2.61 (1H, dd, J = 8.3, 14.0 Hz, H-3b);

_{^{13 C NMR (methanol- d 4,}} 62.5 ㎒) δ: 181.1 (C-1), 156.8 (C-4 '), 131.7 (C-3', C-5 '), 131.3 (C-1'), 116.0 (C-2 ', C-6'), 75.1 (C-2), 41.7 (C-3).

Examples 2-6. Latipolysinin C (Compound 6)

latifolicinin C;

light yellow powder;

MW: 196.20;

mp: 65-67 [deg.] C;

-9.6 < / RTI > ( c 0.4, MeOH);

^{1 H NMR (chloroform- d, 400} ㎒) δ: 6.97 (2H, d, J = 8.4 ㎐, H-3 ', H-5'), 6.65 (2H, d, J = 8.4 ㎐, H-2 ' , H-6 '), 4.39 (1H, dd, J = 4.8, 6.8 ㎐, H-2), 3.72 (3H, s, OCH 3), 3.72 (1H, dd, J = 4.4, 14.0 ㎐, H- 3a), 2.84 (1H, dd, J = 6.8, 14.0 Hz, H-3b);

_{^{13 C NMR (methanol- d 4,}} 100 ㎒) δ: 175.9 (C-1), 155.0 (C-4 '), 130.6 (C-3', C-5 '), 127.7 (C-1'), 115.6 (C-2 ', C -6'), 71.7 (C-2), 52.6 (OCH 3), 39.7 (C-3).

Examples 2-7. Latipolisinin B (Compound 7)

latifolicinin B;

syrup;

MW: 210.23;

-5.0 ( c 0.1, MeOH);

_{^{1 H NMR (methanol- d 4,}} 600 ㎒) δ: 7.07 (2H, d, J = 8.4 ㎐, H-3 ', H-5'), 6.73 (2H, d, J = 8.4 ㎐, H-2 ', H-6'), 4.31 (1H, dd, J = 5.4, 7.2 ㎐, H-2), 4.16 (2H, q, J = 7.2, H-1 "), 2.97 (1H, dd, J = 5.4, 13.8 Hz, H-3a), 2.87 (1H, dd, J = 7.8, 13.8 Hz, H-3b), 1.25 (3H, t, J = 7.2 Hz, H-2 ");

_{^{13 C NMR (methanol- d 4,}} 150 ㎒) δ: 175.6 (C-1), 157.3 (C-4 '), 131.6 (C-3', C-5 '), 129.3 (C-1'), 116.2 (C-2 ', C-6'), 73.5 (C-2), 62.1 (C-1 "), 41.1 (C-3), 14.6 (C-2").

Examples 2-8. Latipolysinin A (Compound 8)

latifolicinine;

syrup;

MW: 238.28;

-6.0 ( c 0.3, MeOH);

^{1 H NMR (chloroform- d, 400} ㎒) δ: 7.02 (2H, d, J = 8.4 ㎐, H-3 ', H-5'), 6.66 (2H, d, J = 8.4 ㎐, H-2 ' , H-6 '), 4.39 (1H, dd, J = 4.8, 6.4 ㎐, H-2), 4.14 (2H, m, H-1 "), 3.03 (1H, dd, J = 4.4, 14.0 ㎐, H-3a), 2.87 (1H, dd, J = 6.4, 14.0 Hz, H-3b), 1.61 , t, J = 7.6 Hz, H-4 ");

¹³ C (chloroform- d , 100 MHz) ?: 174.6 (C-1), 155.0 (C-4 '), 130.8 (C-2 ', C-6'), 71.6 (C-2), 65.9 13.8 (C-4 ").

Examples 2-9. 1- (3 ', 4'-dihydroxyphenyl) -2-hydroxyethan-1-one (Compound 9)

1- (3 ', 4'-dihydroxyphenyl) -2-hydroxyethan-1-one;

amorphous powder;

MW: 168.15;

mp: 178-181 DEG C;

_{^{1 H NMR (Methanol- d 4,}} 400 ㎒) δ: 7.40 (1H, br s, H-2 '), 7.39 (1H, m, overlap, H-5'), 6.84 (1H, d, J = 8.0 Hz, H-6 '), 4.80 (2H, s, H-2);

¹³ C NMR (Methanol- d ₄ , 100 MHz) ?: 198.8 (C-1), 152.8 (C-4 '), 146.8 '), 116.2 (C-5'), 115.5 (C-2 '), 66.0 (C-2).

Examples 2-10. Oresbuchin A (Compound 10)

oresbiusine;

syrup;

MW: 212.20;

_{^{1 H NMR (methanol- d 4,}} 400 ㎒) δ: 6.69 (1H, d, J = 7.6 ㎐, H-5 '), 6.68 (1H, br s, overlap, H-2'), 6.54 (1H, dd, J = 2.0, 8.0 ㎐ , H-6 '), 4.31 (1H, dd, J = 5.2, 7.6 ㎐, H-2), 3.67 (3H, s, OCH 3), 2.91 (1H, dd, J = 5.2, 14.0 Hz, H-3a), 2.79 (1H, dd, J = 7.2, 14.0 Hz, H-3b);

_{^{13 C NMR (methanol- d 4,}} 100 ㎒) δ: 176.0 (C-1), 146.2 (C-3 '), 145.2 (C-4'), 130.0 (C-1 '), 121.9 (C-6 '), 117.7 (C-2 '), 116.3 (C-5 '), 73.5 (C-2), 52.4 (OCH 3), 41.3 (C-3).

Examples 2-11. (+ -) - tradescantin (Compound 11)

(±) -radecethanine;

amorphous powder;

MW: 240.21;

mp: 200-202 [deg.] C;

0 ( c 0.2, MeOH)

UV (MeOH) ? _Max nm (log ? ): 205 (5.29), 235 (5.21), 280 (5.03), 311 (4.96);

IR (KBr) v _max Cm ^-1 : 3356, 1724, 1671, 1595, 1522;

_{^{1 H NMR (methanol- d 4,}} 250 ㎒) and 13 C NMR (methanol- d 4, 62.5 ㎒) data, see table 1;

≪ 1 > H NMR data of Mosher esters (13S and 13R) (chloroform- d , 600 MHz) data, see table 2;

HR-EI-MS m / z 240.0632 [M] + (calcd. For C 11 H 12 O 6, 240.0634).

Examples 2-12. (6 S , 9 R ) - < / RTI >

(6 S, 9 R) -roseoside ;

colorless syrup;

MW: 386.44;

_{^{1 H NMR (methanol- d 4,}} 600 ㎒) δ: 5.92 (1H, dd, J = 4.8, 15.6 ㎐, H-8), 5.91 (1H, br s, H-4), 5.89 (1H, d, J = 15.0 ㎐, H-7 ), 4.46 (1H, m, H-9), 4.38 (1H, d, J = 7.8 ㎐, H-1 '), 3.89 (1H, dd, J = 2.4, 12.0 ㎐ M, H-6'a), 3.67 (1H, dd, J = 6.0, 12.0 Hz, H-6'b), 3.38 ), 3.27 (1H, m, H-3 '), 3.21 (1H, dd, J = 7.8, 9.0 Hz, H-2'), 2.56 (1H, d, J = 16.8 Hz, H- (1H, d, J = 16.8 Hz, H-2b), 1.96 (3H, d, J = 1.2 Hz, H-11), 1.33 (3H, d, J = 6.0 Hz, H- , s, H-12), 1.07 (3H, s, H-13);

¹³ C-NMR (methanol- d ₄ , 150 MHz) ?: 201.3 (C-3), 167.4 (C-5), 135.4 (C-1 '), 80.2 (C-6), 78.3 (C-5'), 78.2 (C-3 '), 77.4 ), 63.0 (C-6 '), 50.9 (C-2), 42.6 (C-1), 24.8 11).

Examples 2-13. Trade ス canthoside (Compound 13)

tradescantoside;

MW: 492.43;

mp: 223-228 [deg.] C;

-46.8 (c 0.2, MeOH);

UV (MeOH)? _Max nm (log?): 205 (4.55), 246 (4.23), 293 (4.14), 324 (4.19);

IR (KBr)? _Max cm ^-1 : 3291, 1689, 1597, 1515;

¹ H NMR (Methanol- d ₄ , 600 MHz) and ¹³ C NMR (Methanol- d ₄ , 150 MHz) data, see table 3;

HR-ESI-MS (positive) m / z 515.1166 [M + Na] ⁺ (calcd for C ₂₃ H ₂₄ O ₁₂ Na ⁺ , 515.1160);

HR-ESI-MS (negative) m / z 491.1187 [MH] ^- (calcd for C ₂₃ H ₂₃ O ₁₂ ^- , 491.1195).

Position δ _C δ _H  (multiplicity, J  in Hz) One 173.1 - 2 40.9 2.79 (dd, J = 4.3, 15.8)
2.50 (dd, J = 8.0,15.8) 3 70.6 5.29 (dd, J = 4.3,8.0) 4 199.4 - One' 127.8 - 2' 116.6 7.37 (s) 3 ' 146.8 - 4' 152.9 - 5 ' 116.1 6.77 (d, J = 8.3) 6 ' 123.7 7.39 (d, J = 8.3) OCH ₃ 52.7 3.61 (s)

Position 13S ( δ _H ) 13R ( δ _H ) 2a 2.96 (dd, J = 4.2, 16.8 Hz)
or 2.92 (dd, J = 4.2, 16.8 Hz) 2.92 (dd, J = 4.2, 16.8 Hz)
or 2.96 (dd, J = 4.2, 16.8 Hz) 2b 2.90 (dd, J = 9.0, 16.8 Hz)
or 2.84 (dd, J = 9.0, 16.8 Hz) 2.84 (dd, J = 9.0, 16.8 Hz)
or 2.90 (dd, J = 9.0, 16.8 Hz) 3 6.41 (dd, J = 4.2, 9.0 Hz)
or 6.38 (dd, J = 4.2, 9.0 Hz) 6.38 (dd, J = 4.2, 9.0 Hz)
or 6.41 (dd, J = 4.2, 9.0 Hz)

Position δ _C δ _H  (multiplicity, J  in Hz) One 124.3 - 2 120.1 7.88 (d, J = 1.8) 3 146.4 - 4 153.2 - 5 116.9 6.92 (d, J = 8.4) 6 127.4 7.67 (dd, J = 1.8,8.4) 7 170.1 - One' 104.0 4.91 (d, J = 7.8) 2' 74.9 3.58 (m) 3 ' 77.6 3.56 (m) 4' 71.9 3.48 (m) 5 ' 75.9 3.79 (m) 6 ' 64.9 4.61 (dd, J = 1.8, 12.0)
4.37 (dd, J = 7.2, 12.0) One'' 128.0 - 2'' 112.2 7.18 (d, J = 1.8) 3 '' 149.5 - 4'' 150.7 - 5 '' 116.7 6.85 (d, J = 8.4) 6 '' 124.3 7.12 (dd, J = 1.8,8.4) 7 '' 147.3 7.63 (d, J = 15.6) 8'' 115.5 6.48 (d, J = 15.6) 9 '' 169.4 - OCH ₃ 56.7 3.93 (s)

<Example 3> Measurement of inhibitory activity of protein tyrosine dephosphorylase 1B>

P-nitrophenyl phosphate (p-NPP) is converted to p-nitrophenol (p-NP) as a substrate by protein tyrosine dephosphorylase 1B, (Cui, L. et al., 2006).

To a 96 wells microtiter plate was added 40 μl of protein tyrosine dephosphorylase 1B (human) dissolved in buffer (50 mM citrate (pH 6.0), 0.1 M NaCl, 1 mM EDTA (ethylenediaminetetraacetic acid) and further each of the compounds of the invention dissolved in a recombinant, BIOMOL ^® International LP, Plymouth Meeting, PA), 1mM DTT (dithiothreitol) and DMSO. Then, the reaction was performed at 37 캜 for 10 minutes, followed by addition of 50 2 of 2 mM p-NPP, reaction at 37 캜 for 20 minutes, and termination of the reaction by treatment with 10 M NaOH. The amount of the remaining p-NPP was measured by a microplate spectrophotometer (Molecular Devices, Sunnyvale, Calif., USA) at 405 nm and expressed as IC ₅₀ (the half maximal inhibitory concentration) in Table 4 below.

Condition 1B inhibitory effect of protein tyrosine dephosphorylase (IC ₅₀ ) The methanol extract of Example 1 4.79 g / ml The mixed fraction of ethyl acetate and n-butanol in Example 1 1.55 ㎍ / ml Urosolic acid 1.3 [mu] g / ml (2.8 [mu] M) Compound 1 2 [mu] g / ml (15.1 [mu] M) Compound 2 1.6 [mu] g / ml (7.8 [mu] M) Compound 3 4.9 [mu] g / ml (25.7 [mu] M) Compound 4 11.6 [mu] g / ml (64.6 [mu] M) Compound 5 7.3 [mu] g / ml (40.2 [mu] M) Compound 6 1.3 [mu] g / ml (6.8 [mu] M) Compound 7 7.1 [mu] g / ml (33.8 [mu] M) Compound 8 1.1 [mu] g / ml (4.6 [mu] M) Compound 9 8.9 [mu] g / ml (53 [mu] M) Compound 10 1.4 [mu] g / ml (6.4 [mu] M) Compound 11 4.2 [mu] g / ml (17.6 [mu] M) Compound 12 16.2 [mu] g / ml (41.8 [mu] M) Compound 13 5.3 [mu] g / ml (10.8 [mu] M)

Referring to the results of Table 4, the purple starch extract of the present invention and the compound isolated therefrom showed excellent inhibitory effect on protein tyrosine dehydrogenase 1B similar to uric acid, which is a positive control, and thus, treatment of metabolic diseases such as diabetes or obesity The effect is expected to be good.

< Example  4. Toxicity test>

Example  4-1. Acute toxicity

This study was conducted to investigate the toxicity of the extract of Purple Bay bark extract of the present invention to an animal body in an acute (within 24 hours) when an excessive amount was taken in a short period and to determine the mortality rate. Twenty ICR mice were prepared, and 10 mice were assigned to each group. In the control group, only 30% PEG-400 alone was administered, and the experimental group was orally administered the purple early berry extract of the present invention at a concentration of 1.0 g / kg. After 24 hours of administration, the respective mortality rates were examined. As a result, both the control group and the control group administered with the purple starch extract survived.

Example 4-2. Organ organs toxicity test in experimental group and control group

The long-term toxicity test was carried out on the C57BL / 6J mice in order to investigate the effect of the purple early berry extract of the present invention at a concentration of 1.0 g / kg and the control group Blood samples were taken from the animals 8 weeks later and the concentrations of glutamate-pyruvate transferase (GPT) and blood urea nitrogen (BUN) in the blood were measured using a Select E (vital scientific NV, Netherland) instrument. As a result, GPT, which is known to be related to hepatotoxicity, and BUN, which is known to be related to renal toxicity, showed no significant difference compared to the control group. In addition, liver and kidney were cut from each animal and histological observation was performed with an optical microscope through a conventional tissue section production process, but no abnormal abnormalities were observed.

&Lt; Formulation Example 1 >

Formulation Example 1-1. Manufacture of tablets

200 g of the purple bass early extract of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. To this mixture was added a 10% gelatin solution, which was pulverized and passed through a 14-mesh sieve. This was dried, and a mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into tablets.

Formulation Example 1-2. Injection preparation

1 g of the purple bark extract of the present invention, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was placed in a bottle and sterilized by heating at 20 DEG C for 30 minutes.

<Formulation Example 2: Food Preparation>

Formulation Example 2-1. Manufacture of cooking seasonings

The purple starch extract of the present invention was added to the cooking seasoning at 1% by weight to prepare a cooking sauce for health promotion.

Formulation Example 2-2. Manufacture of flour food products

The purple starch extract of the present invention was added to wheat flour in an amount of 0.1% by weight, and a bread, a cake, a cookie, a cracker and a noodle were prepared using the mixture to prepare a health improving food.

Preparation Example 2-3. Manufacture of soups and gravies

The health enhancing soup and the juice were prepared by adding the purple berry extract of the present invention to the soup and juice at 0.1 wt%.

Formulation Example 2-4. Manufacture of dairy products

The purple starch extract of the present invention was added to milk in an amount of 0.1% by weight and various dairy products such as butter and ice cream were prepared using the milk.

Formulation Example 2-5. Vegetable juice manufacturing

The vegetable juice for health promotion was prepared by adding 0.5 g of the purple starch extract of the present invention to 1,000 ml of tomato juice or carrot juice.

Formulation example  2-6. Fruit juice  Produce

The fruit juice for health promotion was prepared by adding 0.1 g of the purple starch extract of the present invention to 1,000 ml of apple juice or grape juice.

Claims (11)

delete delete (. Tradescantia spathacea Sw) purple only to early detached from the formula 1 (S) -2- hydroxy-3- (4'-hydroxyphenyl) propionic acid (compound 4), (R) -2- hydroxy- (Compound 5), Latipolisinin C (Compound 6), Latipolysinin B (Compound 7), Latipolysinin A (Compound 8), Oresbuchin A (Compound 10) and trade scantoside (Compound 13) as an active ingredient. The composition for preventing or treating obesity or diabetes according to claim 1,
[Chemical Formula 1]

delete delete delete (. Tradescantia spathacea Sw) purple only to early detached from the formula 1 (S) -2- hydroxy-3- (4'-hydroxyphenyl) propionic acid (compound 4), (R) -2- hydroxy- (Compound 5), Latipolisinin C (Compound 6), Latipolysinin B (Compound 7), Latipolysinin A (Compound 8), Oresbuchin A (Compound 10) and tradescant cancide (Compound 13) as an active ingredient. The health functional food for preventing or ameliorating obesity or diabetes.
[Chemical Formula 1]

delete Extracting a purple early twig ( Tradescantia spathacea Sw.) With water, C1 to C4 lower alcohols or a mixed solvent thereof to prepare a purple early berry extract; Sequentially fractionating the purple bass early extract using dichloromethane, ethyl acetate and n-butanol; And (S) -2-hydroxy-3- (4'-hydroxyphenyl) propionic acid (Compound 4), (R) -2-hydroxy- (Compound 5), Latipolysinin C (Compound 6), Latipolysinin B (Compound 7), Latipolysinin A (Compound 8), Oresbuchin A (Compound 10) (13). &Lt; / RTI &gt;
[Chemical Formula 1]

delete A novel compound tradeascantoide having the following chemical structure (Compound 13).

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