KR101752247B1 - A composition comprising compounds isolated from Selaginella tamariscina for preventing or treating metabolic disorder - Google Patents

Abstract

The present invention relates to a composition for preventing or treating a metabolic disease comprising a compound separated from bupjosone. The compound isolated from Bucheon can be effectively used as a composition for preventing or treating metabolic diseases because it has an excellent effect of inhibiting protein tyrosine dephosphorylase 1B or increasing glucose uptake.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing or treating a metabolic disease,

The present invention relates to a composition for preventing or treating a metabolic disease comprising a compound isolated from Selaginella tamariscina .

In recent years, the development of cardiovascular and metabolic diseases including cancer has been increasing in spite of the recent developments of modern life science related to changes in dietary habits and aging of population and various stresses caused by recent economic development. Particularly, among the metabolic diseases, diabetes is a chronic wasting disease characterized by an abnormal deficiency of insulin or a dysfunction due to resistance, and is a disease that causes various complications such as systemic insufficiency and resistance decrease, vascular disorder, cerebral infarction, myocardial infarction to be. In addition, the World Health Organization (WHO) estimated that 350 million people are suffering from diabetes and that by 2030 the number will increase by a factor of two (Danaei, G. et al., 2011).

Diabetes mellitus is divided into two types according to the cause and the pathogenesis of the disease. The insulin-dependent insulin-dependent diabetes mellitus is caused by the fact that the beta cells of Langerhans is destroyed by specific human lymphocyte antigen (HLA) Type 1 diabetes mellitus is an insulin-independent type 2 diabetes mellitus induced by increased resistance to insulin in peripheral tissues such as muscle, liver, and adipose tissue due to lack of exercise, obesity, overeating, and stress. In particular, due to the aging of modern society and changes in lifestyle, type 2 diabetes accounts for more than 90% of all diabetics, and the number is steadily increasing. The main cause of type 2 diabetes is insulin resistance, a condition in which the response to a given amount of insulin is less than normal, and is generally caused by genetic and environmental factors (Hossain, P. et al. , 2007).

Meanwhile, GLUT4 (glucose transporter 4) is a glucose transporter that transports glucose to the cell membrane and glucose uptake. This process is a step of regulating glucose uptake in each cell and promoted by insulin. When GLUT4 transports glucose into the blood cells, it transforms glucose into glucose and oxidizes it to fatty acids. In muscle cells, the absorption of amino acids to synthesize proteins is promoted. In other tissues other than fat and muscle cells, glucose enters the cells by diffusion mechanism, regardless of insulin. However, when insulin is present in fat and muscle cells, GLUT4 is transferred to the cell membrane and glucose enters the fat and muscle cells. In this way, the insulin sensitivity of glucose into the cells only by the insulin, and if the insulin function is not reduced or secreted, GLUT4 does not migrate to the cell membrane and glucose does not flow into the fat and muscle cells, (Huang, S. et al., 2007; Lee, WY et al., 2008). In this case, since glucose absorption is not smooth and tissue cells can not be effectively used, monitoring glucose uptake by cells is particularly useful for diagnosis of metabolic diseases.

Protein tyrosine phosphatase 1B (PTP1B) induces the dephosphorylation of insulin receptors and insulin receptor substrates to inhibit the signal transduction pathway of insulin, as shown in Fig. 1 below. Is known as an enzyme that causes insulin resistance. In addition, the protein tyrosine dephosphorylase is also known to cause obesity by inhibiting the leptin signal transduction mechanism and inhibiting phosphorylation induced by leptin receptor and Jak in the signal transduction of leptin (Malamas, MS et al., 2000) .

[Reference Figure 1]

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, in rats in which protein tyrosine phosphatase 1B (PTP1B) gene was removed, insulin resistance was eliminated and type 2 diabetes was not induced, and obesity was inhibited (Elchebly, M. et al., 1999), and substances that inhibit protein tyrosine phosphatase 1B (PTP1B) have been shown to exhibit antidiabetic effects (Klaman, LD et al., 2000). The inhibitor of various tyrosine dephosphorylases including the protein tyrosine dephosphorylase 1B that has entered into clinical practice to date is shown in Reference 2 in the following reference. Most of the compounds are eliminated in clinical trials because of low bioavailability, toxicity and side effects. Therefore, it is required to develop an inhibitor derived from a highly safe natural product (Johnson, T. O. et al., 2002).

[Reference Figure 2]

Bugazon ( Selaginella tamariscina ) is a perennial herb with a bamboo plant, Lycoris spp. It is an evergreen perennial herb that grows in the gaps between Jeju Island and Ulleungdo, southern part, central part, northern part. It is about 20㎝ tall and leaves are 1.5 ~ 2㎜ long and thread-shaped. When wet, branches spread in all directions; when dried, they drift inward to form a ball; The spores are 0.5 ~ 1.5㎝ in length and 2mm in diameter.

It has been traditionally used in the treatment of inflammation, chronic infection, dysmenorrhea, uterine bleeding, hematuria, hyperglycemia, and the like (Jiwon et al., 1990) and flavonoids, biflavonoids, lignans lignans, selaginellins and phenols (Zheng, XK et al., 2011; Weng, JK et al., 2013).

Korean Patent Laid-Open Publication No. 2013-0081852 discloses that Buchoeson extract or fraction has an immunity-enhancing effect and Korean Patent No. 633344 discloses that there is an effect of preventing or treating acute or chronic degenerative brain diseases have. In Korean Patent Laid-Open Publication No. 2013-0113626, a study on the prevention and treatment of diabetes or obesity using bouchones extract has been reported. However, a previous report confirming that a compound isolated from bouchones has a therapeutic effect on obesity or diabetes not yet. Therefore, the inventors of the present invention have completed the present invention by confirming that the compound isolated from Bucheoson inhibits the activity of protein tyrosine dephosphorylase 1B or increases the absorption of glucose.

Korean Registered Patent No. 633344, a composition for preventing or treating acute or chronic degenerative brain diseases, including extracts of Ganoderma lucidum, is registered on Jan. 06, 2006. Korean Patent Laid-Open Publication No. 2013-0081852, a composition for enhancing immunity comprising bouczone extract or a fraction thereof, disclosed on Jul. 18, 2013. Korean Patent Laid-Open Publication No. 2013-0113626, a composition for preventing or treating diabetes or obesity comprising an extract of a fern as an active ingredient, disclosed on October 16, 2013.

(1990), "A Study on the Development of a New Genetic Algorithm", Proc. 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. 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. Hossain, P. et al., Obesity and diabetes in the developing world-a growing challenge, Engl. J. Med., 356 (3), 213-215, 2007. Huang, S. et al., The GLUT4 glucose transporter, Cell Metab., 5 (4), 237-252, 2007. 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. Lee, W. Y. et al., Type 2 Diabetes Mellitus and Retinol-Binding Protein 4, Korean Diabetes J., 32, 295-300, 2008. 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. 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. Weng, J. K. et al., Chemodiversity in Selaginella: a reference system for parallel and convergent metabolic evolution in terrestrial plants, Frontiers in Plant Science, 4, 119, 2013. Zheng, XK et al., Anti-diabetic activity and potential mechanism of total flavonoids of Selaginella tamariscina (Beauv.), Spring in rats induced by high fat diet and low dose STZ, J. Ethnopharmacol., 137 (1), 662-668 . 2011.

It is an object of the present invention to provide a composition for the prevention or treatment of metabolic diseases comprising a compound isolated from brucite.

The present invention relates to a composition for preventing or treating a metabolic disease comprising a compound isolated from Selaginella tamariscina . More particularly, the present invention relates to a method for producing a cellulosin, which comprises separating from a bupcrest, selaginellin (compound 1), selariscinin A (compound 2), selaginellin M (compound 3) (selariscinin B, compound 4), selariscinin C (compound 5), selariscinin D (compound 6), selariscinin E (compound 7), robustaflavone, Compound 8), cupressuflavone (compound 9), taiwaniaflavone (compound 10) and 3,8 "-biapigenin (3,8" -biapigenin, compound 11) To a composition for preventing or treating a metabolic disease comprising at least one compound.

[Chemical Formula 1]

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

These compounds have the effect of inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B) or increasing the uptake of glucose (glucose uptake).

The composition is characterized in that it is formulated into a pharmaceutical dosage form with the addition of a pharmaceutically acceptable carrier, excipient or diluent.

In addition, the present invention relates to a method for the treatment and / or prophylaxis of seulaginellin (compound 1), selariscinin A (compound 2), selaginellin M (compound 3), selalininin (Selariscinin B, compound 4), selariscinin C (compound 5), selariscinin D (compound 6), selariscinin E (compound 7), robustaflavone , Compound 8), cupress flavone (compound 9), taiwaniaflavone (compound 10) and 3,8 "-biapigenin (3,8" -biapigenin, compound 11) And to a health functional food for preventing or ameliorating a metabolic disease comprising at least one compound selected from the group consisting of

In another aspect, the present invention provides a pharmaceutical composition comprising selariscinin A (compound 2), selariscinin B (compound 4), selariscinin C, compound 5, (Selariscinin D, compound 6) and selariscinin E (selariscinin E, compound 7).

(2)

The present invention relates to a method for producing boucchons extract, which comprises extracting buppon's hands with water, C1 to C4 lower alcohols or a mixed solvent thereof; Sequentially fractionating the bamboo shoot extract with dichloromethane, ethyl acetate and n-butanol; And each of the above fractions was analyzed by chromatography to determine the concentration of selariscinin A (compound 2), selariscinin B (compound 4), selariscinin C (compound 5) The present invention relates to a method for separating at least one compound selected from the group consisting of selariscinin D (compound 6) and selariscinin E (selariscinin E, compound 7).

Hereinafter, the present invention will be described in detail.

The present invention relates to a composition for the prevention or treatment of metabolic diseases comprising at least one compound selected from the group of compounds of the formula (1) isolated from Selaginella tamariscina .

The compound can be obtained by fractionating the Buchoeson's water, the C1 to C4 lower alcohol or the mixed solvent extract thereof by chromatography. The C1 to C4 lower alcohol may be methanol, ethanol, propanol, isopropanol, butanol or the like . Preferably, the benthosolid portion is extracted with water, a lower alcohol of C1 to C4 or a mixed solvent thereof to obtain a bushsox extract, and the bushsox extract is sequentially fractionated using dichloromethane, ethyl acetate and n-butanol, To obtain fractions, and then fractionating the above fractions by chromatography.

The chromatography can be carried out by silica gel column chromatography, RP-18 column chromatography, thin layer chromatography (TLC), ion exchange resin chromatography ), Medium pressure liquid chromatography, silica gel vacuum 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 at least one compound selected from the group of compounds of the formula (1) separated from bupjosone. The pharmaceutical composition containing the compound can be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like oral preparation, external preparation, suppository and sterilized injection solution according to a conventional method 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 or 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 the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The dosage of the pharmaceutical composition comprising the compound of the present invention will vary depending on the age, sex, body weight, the specific disease or condition to be treated, the severity of the disease or condition, the route of administration, and the judgment of the prescriber. 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 compositions comprising the compounds of the present invention may be administered to mammals such as rats, livestock, humans, and the like in a variety of 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 compound of the present invention 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 health functional food for preventing or ameliorating a metabolic disease such as diabetes or obesity, which comprises at least one compound selected from the group of compounds of formula (1) isolated from bupjosone and a pharmaceutically acceptable food supplementary additive to provide. The compound may be added in an amount of 0.001 to 100% by weight to the health functional food of the present invention. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids, and examples of foods to which the compound of the present invention can be added include various foods, beverages, gums, tea, vitamins .

The present invention relates to a composition for the prevention or treatment of metabolic diseases comprising a compound isolated from Buddhism. The compound isolated from Bucheon can be effectively used as a composition for preventing or treating metabolic diseases because it has an excellent effect of inhibiting protein tyrosine dephosphorylase 1B or increasing glucose uptake.

1 is a result of MTT assay for confirming the cell survival rate of the compounds 1 to 11 of the present invention.
2 is a figure showing a correlation (arrow) of the compounds 2, 4, and ^{5 1 H- 1 H COSY (bold} lines) and the ¹ H- ¹³ C HMBC of.
Figure 3 is an illustration showing the correlation between (arrow) of compound 6 and ^{7 1 H- 1 H COSY (bold} lines) and the ¹ H- ¹³ C HMBC of.

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 bupjosone-derived compound >

The top part of the buguson ( Selaginella tamariscina ) used in the present invention was purchased in Yeongcheon market, Gyeongbuk, Korea in January, 2010. The above-mentioned foot-and-mouth surface portion (10 kg) was repeatedly subjected to ultrasonic treatment four times at 45 캜 for 10 hours in methanol (10 L) to obtain 1.5 kg of methanol extract. The methanol extract was suspended in 2 L of water and the dichloromethane fraction (470 g), the ethyl acetate fraction (2 L), the ethyl acetate (2 L) and the n-butanol (2 L) (150 g) and the n-butanol fraction (550 g) and the fraction (220 g) containing the water layer residue were obtained and the compound of the present invention was isolated from the ethyl acetate fraction having a relatively high glucose absorption effect in adipocytes.

The ethyl acetate fraction was purified by silica gel column chromatography (column size: 20 占 80 cm, particle size: 63-200 占 퐉 according to concentration gradient elution with dichloromethane: methanol (10: 1 → 0: 1 [v: ) To obtain five small fractions (ST.1 to ST.5). Among them, the small fraction ST.2 with a relatively high glucose uptake effect was purified by RP-18 column chromatography (column size: 4.5) according to the concentration gradient elution gradient of methanol: water (6: 4 → 1: 0 [v: v] × 60 cm, particle size: 40-63 μm) to obtain five small fractions (ST.2.1 to ST.2.5). Of these small fractions, ST.2.2 was obtained by high performance liquid chromatography (Gilson HPLC system, YMC _C18 column, column size: 10 x 250 mm, particle size: 5 탆, UV: 225 nm, mobile phase: (V / v) MeCN, 33-41 min: 100% MeCN, 41-40 min: 30-33 min: acetonitrile (MeCN) 43 minutes: 100 ~ 38% [v / v] MeCN, 43 ~ 45 min: were isolated 38% [v / v] MeCN ) to give the compound 6 (selariscinin D, 4.8㎎, t R = 20.7 min) using a.

In another condition, the small fraction ST.2.2 was purified by high performance liquid chromatography (RS Tech Optima Pak C ₁₈ Column, column size: 10 x 250 mm, particle size: 10 탆, UV: 225 nm, mobile phase: acetonitrile containing 0.1% formic acid-water; V / v MeCN, 33-41 min: 100% MeCN, 41-43 min: 100-38% [v / v] were isolated 38% [v / v] to give the compound 4 (selariscinin B, 4.4㎎, t R = 20.7 min) using MeCN): / v] MeCN, 43 ~ 45 minutes.

The small fraction ST.2.4 was purified by high performance liquid chromatography (Gilson HPLC system, RP C18 column, column size: 10x250) according to isocratic elution conditions (solvent: 60% [v / v] methanol aqueous solution containing 0.1% formic acid) ㎜, particle size: 10㎛) in fraction to give the compound 7 (E selarircinin, 15.8㎎, t _R = 32.6 min.), another isocratic elution conditions (solvent: 0.1% of 64% formic acid containing [v / v ] aqueous solution of methanol, UV: 225㎚) was used to separate the compound 3 (selaginellin M, 16.3㎎, t R = 26.5 min) and compound 5 (selariscinin C, 2.8㎎, t R = 30.2 min).

The small fraction ST.3 was fractionated by silica gel column chromatography according to elution conditions of dichloromethane: methanol (1: 1? 0: 1 [v: v]) to obtain 10 small fractions (ST.3.1 to ST.3.10 Among them, ST.3.3, ST.3.4 and ST.3.5 were analyzed by RP-18 column chromatography (concentration gradient elution: methanol: water (4: 6 → 4: 1 [v: v] Compound 8 (robustaflavone, 7.8 mg) and Compound 9 (cupressuflavone, 5.6 mg) were separated using a column (column size: 5.0 x 20 cm, particle size:

The small fraction ST.4 was purified by RP-18 column chromatography (column size: 3.0 × 20 cm, particle size: 40-40 nm) according to concentration gradient elution conditions of methanol: water (5: 5 → 5: 1 [v: v] 63 占 퐉) to obtain Compound 1 (selaginellin, 115.6 mg) and Compound 2 (selariscinin A, 65.0 mg). In another condition, the small fraction ST.4 was purified by silica gel column chromatography (column size: 3.0 x 20 cm, particle size: 3.0 x 10 cm) according to elution conditions of n-hexane: acetone (3: 1 to 1: 2 [v: : 40-63 占 퐉), 10 small fractions (ST.4.1 to ST.4.10) were isolated. Among them, ST.4.3 was fractionated by RP-column chromatography (particle size: 40-63 mu m) according to isocratic elution conditions (methanol: water, 50:50 [v / v]) to give compound 10 (taiwaniaflavone, 3.8 mg ) And the small fraction ST.4.5 was subjected to RP-column chromatography (particle size: 40-63 μm) as a gradient elution condition of methanol: water (1: 1 → 9: 1 [v: v] To isolate compound 11 (3,8 " -biapigenin, 4.5 mg).

≪ Example 2: Identification of physicochemical structure of a compound separated from Bucheoson '

Example 2-1. Selaginellin (Compound 1)

selaginellin;

M.W. : 512.56;

¹ H (400 MHz) and ¹³ C (100 MHz) NMR Data in MeOH- d ₄ (see Table 1).

Example 2-2. Cellarinin A (Compound 2)

seliccicine;

(S) -4 - [(4' -hydroxy-4- (hydroxymethyl) -3 - ((4-hydroxyphenyl) ethynyl) biphenyl-2-yl) (4-hydroxyphenyl) methylene] -2,5-cyclohexadien-1 -one;

M.W. : 512.56;

purple amorphous powder (acetone);

: +105.03 ( c 0.5, MeOH);

UV ( c 0.025, MeOH) [ lambda] _max nm: 199, 265, 299 and 440;

IR v _max (KBr) cm ^-1 : 3394 (OH), 2943 (CH), 2203 (C? C), 1641, 1631 (C? C), 1381 (CH), 1077, 1045 (CO);

¹ H (400 MHz) and ¹³ C (100 MHz) NMR Data in MeOH- d ₄ (see Table 1);

HREIMS m / z: 512.1626 [M ] + (calcd for C 34 H 24 O 5, 512.1624).

Examples 2-3. Cellaginellin M (Compound 3)

selaginellin M;

M.W. : 526.59;

¹ H (400 MHz) and ¹³ C (100 MHz) NMR Data in MeOH- d ₄ (see Table 1).

Examples 2-4. Cellarinin B (Compound 4)

selicicine B;

2- (hydroxybis (4-hydroxyphenyl) methyl) -3 - ((4-hydroxyphenyl) ethynyl) -4- (hydroxymethyl) -biphenyl-2 ', 4'-diol;

M.W. : 546.58;

greenish-pink amorphous powder;

: 4.70 ( c 0.25, MeOH);

UV ( c 0.025, MeOH) [ lambda] _max nm: 199, 298 and 440;

IR v _max (KBr) cm ^-1 : 3386 (OH), 2943 (CH stretching), 2205-2198 (C? C), 1641, 1599 (C? C), 1453, 1379 , 1041 (CO), 887, 669;

¹ H (400 MHz) and ¹³ C (100 MHz) NMR Data in acetone- d ₆ (see Table 2);

HREIMS m / z: 546.1683 [M ] + (calcd for C 34 H 26 O 7, 546.1679).

Example  2-5. Cellarinin  C ( selariscinin  C, compound 5)

selicicine C;

2- (hydroxybis (4-hydroxyphenyl) methyl) -3 - ((4-hydroxyphenyl) ethynyl) -4- (methoxymethyl) -biphenyl-2 ', 4'-diol;

M.W. : 560.60;

pale yellow amorphous powder;

: 82.14 ( c 0.1, MeOH);

UV ( c 0.025, MeOH) [ lambda] _max nm: 196, 265, 299, 438;

IR v _max (KBr) cm ^-1 : 3400 (OH), 2201 (C? C), 1641, 1622 (C? C), 1468, 1374 (CH bending), 1154, 996 (CO);

¹ H (400 MHz) and ¹³ C (100 MHz) NMR Data in MeOH- d ₄ (see Table 2);

HREIMS m / z: 560.1839 [M ] + (calcd for C 35 H 28 O 7, 560.1835).

Example  2-6. Cellarinin  D (Compound 6)

selicicine D;

4'-hydroxy-4- (hydroxymethyl) -3 - [(4-hydroxyphenyl) ethynyl] biphenyl-2-carboxylic acid;

M.W. : 360.37;

red amorphous powder;

_{IR v max (KBr): 3394} (OH), 2943 (CH), 2203 (C≡C), 1674 (C = O), 1631 (C = C), 1381 (CH), 1077, and 1045 ㎝ -1 ;

UV ( c 0.02, MeOH)? _Max (log?): 205 (4.99), 264 (4.77), 300 (4.71), 322 (4.57), 420 (4.38) nm;

¹ H (400 MHz) and ¹³ C (100 MHz) NMR data in MeOH- d ₄ , (see Table 3);

HREIMS m / z: 360.1026 [M ] +, (. Calcd for C 22 H 16 O 5, 360.0998).

Example  2-7. Cellarinin  E ( selariscinin  E, compound 7)

seliccinin E;

(2 S) -2,3-dihydro- 5,7,7 ", 2 ', 4', 4"'- hexahydroxy- (5'-8 ") biflavone;

M.W. : 540.48;

yellow amorphous powder;

: 6.3 ( c 0.25, MeOH);

UV ( c 0.02, MeOH) ? _Max (log ? ): 204 (4.53), 221 (4.51), 286 (4.32), 329 (4.14) nm;

IR v _max (KBr) cm ^-1 : 3331 (OH), 2916 (CH), 1670 (C = O), 1593, 1242, 1033

_{CD (MeOH) [θ] 221} +18.6, [θ] 286 -8.7, [θ] 330 +4.5;

¹ H (400 MHz) and ¹³ C (100 MHz) NMR data in MeOH- d ₄ , (see Table 3);

HRFABMS m / z: 540.1060 [M ] + (calcd for C 30 H 20 O 10, 540.1056).

Examples 2-8. Roosteraflavone (Compound 8)

robustaflavone;

M.W. : 538.46;

m.p. : 350-352 DEG C;

IR (KBr) cm ^-1 : 3435, 1657, 1405, 1247, 838;

FABMS m / z : 391 [M + H] < ⁺ >;

_{^{1 H-NMR (pyridine- d 5}} , 400 ㎒): δ 7.06 (H-3), 6.77 (H-6, d, J = 2.22 Hz), 6.85 (H-8, d, J = 2.2 ㎐), (H-2 '), 7.17 (H-5', d, J = 8.6 Hz), 7.92 (H-6 ', d, J = 8.6 Hz), 6.93 8 "), 7.92 (H-2 '', 6 '', d, J = 8.6 Hz), 7.17 (H-3 '', 5 '', d, J = 8.6 Hz);

_{^{13 C-NMR (pyridine- d 5}} , 100 ㎒): δ 165.3 (C-2), 104.1 (C-3), 181.9 (C-4), 163.3 (C-5), 100.3 (C-6), (C-2), 123.4 (C-3 '), 166.4 (C-7), 95.3 (C-8), 159.6 ), 161.5 (C-4 '), 117.9 (C-5'), 132.9 (C6 '), 165.0 C-5 "), 105.9 (C-6"), 162.6 (C-7 "), 95.3 1 ''), 129.5 (C-2 '', 6 ''), 117.0 (C-3 '', 5 ''), 162.7 (C-4 '').

Examples 2-9. Caffe leroflavone (Compound 9)

cupressuflavone;

M.W. : 538.46;

m.p. : 360-361 DEG C;

IR (KBr) cm ^-1 : 3424, 1647, 1409, 1245, 836;

FABMS m / z : 391 [M + H] < ⁺ >;

_{^{1 H-NMR (acetone- d 6}} , 400 ㎒): δ 6.81 (2H, s, H-3, 3 "), 6.49 (2H, s, H-6 ', 6"), 7.52 (4H, d, J = 8.7 Hz, H-2 ', 2'',6', 6 ''), 6.76 (4H, d, J = 8.7 Hz, H-3 ', 3'',5', 5 ''');

_{^{13 C-NMR (acetone- d 6}} , 100 ㎒): δ 163.1 (C-2, 2 "), 102.1 (C-3, 3"), 181.8 (C-4, 4 "), 160.5 (C-5 , 5 "), 100.0 (C-6, 6"), 161.0 (C-7, 7 "), 99.9 , 10 "), 121.0 (C-1 ', 1"), 127.5 (C-2', 2 "', 6', 6"''), 161.0 (C-4 ', 4''').

Examples 2-10. TYWNAIA Flavone (Compound 10)

taiwaniaflavone;

M.W. : 538.46;

_{^{1 H-NMR (Methanol- d 4}} , 500 ㎒): δ 6.51 (IH, s, H-3), 6.08 (IH, s, H-6), 7.64 (2H, d, J = 8.5 ㎐, H- 6 '), 6.08 (1H, s, H-8''), 6.57-6.59 (3H, s, H-3', 5 ' , 8.26 (1H, br d, J = 2.0 ㎐, H-2 "'), 7.08 (1H, d, J = 8.5 ㎐, H-5"'), 7.86 (1H, br dd, J = 8.5, 2.0 Hz, H-6 "');

_{^{13 C-NMR (Methanol- d 4}} , 125 ㎒): δ 166.1 (C-2), 109.1 (C-3), 183.9 (C-4), 165.6 (C-5), 103.0 (C-6), (C-1), 129.4 (C-2 '), 117.2 (C-3'), ), 163.4 (C-4 '), 117.2 (C-5'), 129.4 (C-6 '), 165.6 162.8 (C-5), 102.9 (C-6), 162.2 (C-7), 96.7 C-1 "'), 132.8 (C-2''), 125.1 (C-3''), 156.7 ).

Example  2-11. 3.8 " Via Figenin (Compound 11)

3.8 "-biapigenin;

M.W. : 538.46;

^{1 H-NMR (400 ㎒,} DMSO): δ 6.30 (1H, s, H-6), 6.55 (1H, s, H-8), 7.38 (2H, d, J = 8.8 ㎐, H-2 ', (1H, s, H-6 '), 6.71 (2H, d, J = 8.8 Hz, H-3', 5 ' 2H, d, J = 8.8 Hz, H-2 '', 6 ''), 6.81 (2H, d, J = 8.8 Hz, H-3 '', 5 '').

^{13 C-NMR (400 ㎒,} DMSO): δ 163.7 (C-2), 110.3 (C-3), 180.7 (C-4), 162.5 (C-5), 99.0 (C-6), 164.7 (C (C-1), 128.3 (C-2), 115.5 (C-3), 161.4 (C-4 '), 115.4 (C-5'), 128.3 (C-6 '), 164.0 (C-6), 161.8 (C-7), 103.1 (C-8), 155.2 ''), 130.0 (C-2 ''), 116.2 (C-3 ''), 161.4 (C-4 ''), 116.2 (C-5 ''), 130.0 (C-6 '').

Compound 1 ( selaginellin ) Compound 2 ( selariscinin  A) Compound 3 ( selaginellin  M) pos . δ _H  ( J in  ㎐) δ _C , type δ _H  ( J in  ㎐) δ _C , type δ _H  ( J in  ㎐) δ _C , type One 165.6, C 181.7, C 189.4, C 2 6.51 (br d, 8.8) 122.3, CH 6.46 (dd, 2.0, 8.8) 123.3, CH 6.47 (dd, 2.4, 10.0) 128.6, CH 3 7.14 (br d, 8.8) 138.9, CH 7.18 (dd, 2.0, 8.8) 140.6, CH 7.48 (dd, 2.8, 10.0) 142.4, CH 4 131.9, C 131.6, C 131.8, C 5 7.14 (br d, 8.8) 138.9, CH 7.18 (dd, 2.0, 8.8) 140.6, CH 7.59 (dd, 2.8, 10.0) 141.7, CH 6 6.51 (br d, 8.8) 122.3, CH 6.46 (dd, 2.0, 8.8) 123.3, CH 6.44 (dd, 2.4, 10.0) 129.0, CH 7 165.6, C 170.2, C 164.6, C 8 7.14 (br d, 8.8) 138.9, CH 7.18 (dd, 2.0, 8.8) 140.6, CH 6.77 (dd, 2.0, 8.8) 134.2, CH 9 6.51 (br d, 8.8) 122.3, CH 6.46 (dd, 2.0, 8.8) 128.5, CH 6.75 (dd, 2.0, 8.8) 114.7, CH 10 165.6, C 181.7, C 163.1, C 11 6.51 (br d, 8.8) 122.3, CH 6.46 (dd, 2.0, 8.8) 128.5, CH 6.75 (dd, 2.0, 8.8) 114.7, CH 12 7.14 (br d, 8.8) 138.9, CH 7.18 (dd, 2.0, 8.8) 140.6, CH 6.77 (dd, 2.0, 8.8) 134.2, CH 13 131.9, C 131.6, C 132.6, C 14 123.9, C 124.4, C 123.8, C 15 143.0, C 142.8, C 143.1, C 16 7.70 (d, 8.0) 128.9, CH 7.74 (d, 8.0) 128.8, CH 7.72 (d, 7.6) 128.7, CH 17 7.33 (d, 8.0) 131.1, CH 7.38 (d, 8.0) 130.7, CH 7.34 (d, 7.6) 131.0, CH 18 143.6, C 143.9, C 143.5, C 19 142.4, C 142.5, C 143.0, C 20 6.76 (br d, 8.4) 131.2, CH 6.87 (dd, 2.0, 8.4) 130.9, CH 6.85 (dd, 2.0, 8.8) 131.2, CH 21 6.53 (br d, 8.4) 115.9, CH 6.51 (dd, 2.0, 8.4) 115.8, CH 6.54 (dd, 2.0, 8.8) 115.9, CH 22 158.0, C 158.0, C 158.1, C 23 6.53 (br d, 8.4) 115.9, CH 6.51 (dd, 2.0, 8.4) 115.8, CH 6.54 (dd, 2.0, 8.8) 115.9, CH 24 6.76 (br d, 8.4) 131.2, CH 6.87 (dd, 2.0, 8.4) 130.9, CH 6.85 (dd, 2.0, 8.8) 131.2, CH 25 133.1, C 133.1, C 132.7, C 26 4.94 (s) 63.7, CH ₂ 4.94 (s) 63.6, C 4.96 (s) 63.7, CH ₂ 27 84.7, C 84.4, C 84.7, C 28 100.7, C 101.1, C 100.7, C 29 6.98 (br d, 8.8) 134.2, CH 6.97 (dd, 2.0, 8.8) 134.3, CH 6.99 (dd, 2.0, 8.8) 134.7, CH 30 6.62 (br d, 8.8) 116.5, CH 6.62 (dd, 2.0, 8.8) 116.8, CH 6.63 (dd, 2.0, 8.8) 116.5, CH 31 159.6, C 160.5, C 159.7, C 32 6.62 (br d, 8.8) 116.5, CH 6.62 (dd, 2.0, 8.8) 116.8, CH 6.63 (dd, 2.0, 8.8) 116.5, CH 33 6.98 (br d, 8.8) 134.2, CH 6.97 (dd, 2.0, 8.8) 134.3, CH 6.99 (dd, 2.0, 8.8) 134.7, CH 34 114.6, C 114.1, C 114.6, C OCH ₃ 3.77 (s) 56.1, CH ₃

Compound 4 (selariscinin B ^a ) Compound 5 ( selariscinin  C) pos. δ _H  ( J in Hz) δ _C , type δ _H  ( J in Hz) δ _C , type One 156.9, C 157.1, C 2 6.66 (dd, 2.0, 8.8) 115.2, CH 6.58 (dd, 2.0, 8.4) 115.4, CH 3 7.15 (dd, 2.0, 8.8) 131.2, CH 7.10 (dd, 2.0, 8.4) 131.5, CH 4 134.9, C 135.3, C 5 7.15 (dd, 2.0, 8.8) 131.2, CH 7.10 (dd, 2.0, 8.4) 131.5, CH 6 6.66 (dd, 2.0, 8.8) 115.2, CH 6.58 (dd, 2.0, 8.4) 115.4, CH 7 65.8, C 66.3, C 8 7.15 (dd, 2.0, 8.8) 131.2, CH 7.10 (dd, 2.0, 8.4) 131.5, CH 9 6.66 (dd, 2.0, 8.8) 115.2, CH 6.58 (dd, 2.0, 8.4) 115.4, CH 10 156.9, C 157.1, C 11 6.66 (dd, 2.0, 8.8) 115.2, CH 6.58 (dd, 2.0, 8.4) 115.4, CH 12 7.15 (dd, 2.0, 8.8) 131.2, CH 7.10 (dd, 2.0, 8.4) 131.5, CH 13 134.9, C 135.3, C 14 119.7, C 122.1, C 15 143.1, C 138.5, C 16 7.59 (d, 8.0) 126.7, CH 7.42 (d, 7.6) 129.1, CH 17 7.75 (d, 8.0) 119.5, CH 7.67 (d, 7.6) 119.5, CH 18 140.7, C 142.3, C 19 152.9, C 153.9, C 20 7.67 (d, 8.0) 121.5, CH 7.61 (d, 8.4) 121.9, CH 21 6.84 (dd, 2.0, 8.0) 115.6, CH 6.78 (dd, 2.0, 8.4) 115.9, CH 22 158.8, C 159.6, C 23 6.78 (d, 2.0) 113.4, CH 6.71 (d, 2.0) 113.6, CH 24 157.3, C 157.8, C 25 131.8, C 132.1, C 26 4.82 (s) 63.3, CH ₂ 4.63 (s) 74.4, CH ₂ 27 85.3, C 85.7, C 28 102.1, C 102.5, C 29 6.98 (dd, 2.0, 8.8) 133.5, CH 6.87 (dd, 2.0, 8.8) 133.9, CH 30 6.80 (dd, 2.0, 8.8) 116.5, CH 6.69 (dd, 2.0, 8.8) 116.7, CH 31 158.8, C 159.4, C 32 6.80 (dd, 2.0, 8.8) 116.5, CH 6.69 (dd, 2.0, 8.8) 116.7, CH 33 6.98 (dd, 2.0, 8.8) 133.5, CH 6.87 (dd, 2.0, 8.8) 133.9, CH 34 115.5, C 115.9, C OCH ₃ 3.43 (s) 58.9, CH ₃ ^a Compound was measured in acetone- d ₆

Compound 6 ( selariscinin  D) Compound 7 ( selariscinin  E) pos . δ _H  ( J in  ㎐) δ _C δ _H  ( J in  ㎐) δ _C One 123.8 2 143.0 5.42 (1H, dd, 12.8, 2.8) 80.6 3 7.69 (1H, d, 8.0) 129.0 3.18 (1H, dd, 12.8, 16.8)
2.76 (1H, dd, 2.8, 16.8) 44.1 4 7.31 (1H, d, 8.0) 131.0 198.0 5 143.6 168.5 6 142.7 5.87 (1H, d, 2.0) 97.2 7 165.5 165.6 8 4.91 (2H, s) 63.7 5.90 (1H, d, 2.0) 96.4 9 84.7 165.1 10 100.7 103.5 One' 114.6 131.2 2' 6.97 (1H, dd, 8.8, 2.0) 134.2 162.4 3 ' 6.62 (1H, dd, 8.8, 2.0) 116.5 6.38 (1H, s) 100.2 4' 159.6 163.8 5 ' 6.62 (1H, dd, 8.8, 2.0) 116.5 103.4 6 ' 6.97 (1H, dd, 8.8, 2.0) 134.2 7.44 (1H, s) 128.9 One" 133.1 2" 6.75 (1H, dd, 8.4, 2.0) 131.2 166.3 3 " 6.53 (1H, dd, 8.4, 2.0) 115.9 6.60 (1 H, s) 103.4 4" 158.0 184.5 5 " 6.53 (1H, dd, 8.4, 2.0) 115.9 7.41 (1H, d, 8.4) 131.3 6 " 6.75 (1H, dd, 8.4, 2.0) 131.2 7.05 (1H, d, 8.4) 117.0 7 " 157.4 8" 120.8 9 " 156.6 10 " 106.4 One"' 123.4 2"' 7.55 (1H, dd, 8.8, 2.4) 129.6 3 "' 6.79 (1H, dd, 8.8, 2.4) 117.0 4"' 162.7 5 " 6.79 (1H, dd, 8.8, 2.4) 117.0 6 " 7.55 (1H, dd, 8.8, 2.4) 129.6

< Example  3. Measurement of cell viability>

In order to measure the cell viability of the compounds 1 to 11 isolated from Bucheoson in Example 1, an assay of 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide was performed.

Treat the 3T3-L1 cells (American Type Culture Collection, ATCC, Manassas, VA, USA) to 96 well plates (96well microtiter plate) to 1 × 10 ⁴ cells is dispensed and to one of the present compounds 11 to each well such that And cultured for 48 hours. Thereafter, 1 mg / ml of MTT solution was added and reacted at 37 ° C for 1 hour. DMSO (dimethyl sulfoxide) was dissolved and dispersed in formazan crystals, and the resultant was dissolved in a spectrophotometer (Immuno Mini NJ-2300, The absorbance was measured and shown in Fig.

As a result of Fig. 1, the compounds 1 to 11 of the present invention showed similar cell survival rates as those of the control group (untreated group), confirming that no cytotoxicity was observed.

< Example  4. Protein Tyrosine Dephosphorylase  1B &lt; tb &gt; &lt;

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).

Protein tyrosine dephosphorylation enzymes 1B (human, recombinant) was purchased from ^{BIOMOL ® International LP (Plymouth Meeting,} PA). To a 96-well 96-well microtiter plate, a final volume of 110 μl was added to the buffer ((50 mM citrate, pH 6.0), 0.1 M NaCl, 1 mM ethylenediaminetetraacetic acid and 1 mM DTT (dithiothreitol) Each of the inventive compounds 1 to 11 was subjected to a reaction for 10 minutes at 37 캜 after preparing a mixed treatment containing them. The reaction was terminated by treatment with 10 M sodium hydroxide (10M NaOH), and the amount of the remaining p-nitrophenyl phosphate was adjusted to 40% by VERSA max (Molecular Devices, Sunnyvale, CA, USA) microplate reader. The activity of each compound is shown in Table 4 below in terms of IC ₅₀ (the half maximal inhibitory concentration).

Condition 1B inhibitory effect of protein tyrosine dephosphorylase (IC ₅₀ ) The methanol extract of Example 1 121.3 / / ml The ethyl acetate fraction of Example 1 71.5 / / ml Urosolic acid 1.6 mu g / ml (3.5 uM) RK-682 ¹⁾ 1.7 mu g / ml (4.5 uM) Compound 1 8.1 [mu] g / ml (15.9 uM) Compound 2 2.4 [mu] g / ml (4.6 uM) Compound 3 6.1 [mu] g / ml (11.5 uM) Compound 4 11.8 g / ml (21.6 uM) Compound 5 10.9 g / ml (19.4 uM) Compound 6 4.8 [mu] g / ml (13.2 uM) Compound 7 5.3 [mu] g / ml (9.8 uM) Compound 8 3.3 mu g / ml (6.2 uM) Compound 9 5.2 [mu] g / ml (9.6 uM) Compound 10 2.9 g / ml (5.4 uM) Compound 11 2.4 [mu] g / ml (4.5 uM) ¹⁾ Positive control substance (conventional protein tyrosine dephosphorylase 1B inhibitor)

Comparing the results of Table 4, it was confirmed that Compounds 1 to 11 were 10 to 51 times stronger inhibitory activity than the methanol extract of Example 1, and 6 to 30 times more potent than the ethyl acetate fraction of Example 1 It is confirmed that it has a strong inhibitory activity. Therefore, it can be confirmed that the budesonide compound of the present invention shows an excellent inhibitory effect on tyrosine dephosphorylase 1B.

Example 5: Measurement of glucose uptake in adipocytes.

In order to monitor glucose uptake in adipocytes, 2-NBDG (2- (N- (7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino ) -2-deoxyglucose) was used.

96-black well plates were treated with 3T3-L1 cells and 5 μM of the present compounds 1 to 11, respectively, and cultured at 37 ° C and 5% CO ₂ for 24 hours. Then, 2-NBDG was dissolved in PBS (phosphate buffer saline) supplemented with 1% [w / v] bovine serum albumin (BSA), and the final concentration of 2-NBDG was added to each well to a final concentration of 250 μM. After the reaction, the cells were washed twice with PBS. Fluorescence of the remaining cells was measured at 485 nm excitation wavelength and 535 nm emission wavelength using a Perkin Elmer Victor 3 V 1420 Multilabel Plate Counter (Perkin Elmer, USA) and is shown in Table 5.

Condition Fold of induction DMSO One insulin 1.5 Compound 1 1.2 Compound 2 1.3 Compound 3 1.4 Compound 4 1.1 Compound 5 1.2 Compound 6 1.2 Compound 7 0.9 Compound 8 One Compound 9 1.1 Compound 10 1.5 Compound 11 1.4

As a result of Table 5, it can be confirmed that the compounds 3, 10 and 11 show glucose absorption similar to that of insulin, and that the glucose absorption is smooth and the blood glucose lowering effect is excellent.

< Example  6. Toxicity test>

Example  6-1. Acute toxicity

The present experiment was conducted to investigate toxicity to the animal body in an acute (within 24 hours) when the excessive amount of selariscinin A (Compound 2) of the present invention was consumed in a short period and to determine the mortality. Twenty ICR mice were prepared, and 10 mice were assigned to each group. In the control group, 30% PEG-400 alone was administered, and the experimental group was orally administered with 1.0 g / kg of selariscinin A (compound 2) of the present invention. After 24 hours of administration, the mortality rate was examined. As a result, the control group and the cell lineininin A (compound 2) survived.

Example 6-2. Organ organs toxicity test in experimental group and control group

The long-term toxicity test was carried out on C57BL / 6J mice in order to investigate the effect of each of the organ (organs) of the animal on a 1.0 g / kg concentration of selariscinin A (compound 2) And 8 weeks after the administration of the vehicle alone, blood was collected from the animals and the concentration of glutamate-pyruvate transferase (GPT) and blood urea nitrogen (BUN) was measured using Select E (vital scientific NV, Netherland) Respectively. 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 selariscinin A (Compound 2) 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 selariscinin A (Compound 2) 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

1% by weight of selariscinin A (compound 2) of the present invention was added to the cooking seasoning to prepare a cooking sauce for health promotion.

Formulation Example 2-2. Manufacture of flour food products

A food for health promotion was prepared by adding 0.1% by weight of selariscinin A (Compound 2) of the present invention to wheat flour and preparing bread, cake, cookie, cracker and noodle by using this mixture.

Preparation Example 2-3. Manufacture of soups and gravies

Health enhancing soup and juice were prepared by adding selarcinin A (compound 2) of the present invention to soup and juice at 0.1 wt%.

Formulation Example 2-4. Manufacture of dairy products

The fermentation broth of the present invention (selariscinin A, compound 2) 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

0.5 g of selariscinin A (Compound 2) of the present invention was added to 1,000 ml of tomato juice or carrot juice to prepare health promotion vegetable juice.

Formulation example  2-6. Fruit juice  Produce

Healthy fruit juice was prepared by adding 0.1 g of selariscinin A (Compound 2) of the present invention to 1,000 ml of apple juice or grape juice.

Claims (11)

Selaginellin A (compound 1), selarisinin A (compound 2), selaginellin M (compound 3), selalininin B (compound 2), and the like, which are isolated from the genus Selaginella tamariscina , (selariscinin B, compound 4), selariscinin C (compound 5), selariscinin D (compound 6), selariscinin E (compound 7), robustaflavone, Compound 8), cupressuflavone (compound 9), taiwaniaflavone (compound 10) and 3,8 "-biapigenin (3,8" -biapigenin, compound 11) A composition for preventing or treating obesity or diabetes, which comprises at least one compound.
[Chemical Formula 1]

delete The method according to claim 1,
Wherein said compound inhibits the activity of protein tyrosine phosphatase 1B (PTP1B). 2. A composition for preventing or treating obesity or diabetes according to claim 1, wherein said compound inhibits the activity of protein tyrosine phosphatase 1B (PTP1B). The method according to claim 1,
Wherein said compound increases glucose uptake. &Lt; RTI ID = 0.0 &gt; 21. &lt; / RTI &gt; The method according to claim 1,
Wherein the composition is formulated into a pharmaceutical dosage form by addition of a pharmaceutically acceptable carrier, excipient or diluent. Selaginellin A (compound 1), selarisinin A (compound 2), selaginellin M (compound 3), selalininin B (compound 2), and the like, which are isolated from the genus Selaginella tamariscina , (selariscinin B, compound 4), selariscinin C (compound 5), selariscinin D (compound 6), selariscinin E (compound 7), robustaflavone, Compound 8), cupressuflavone (compound 9), taiwaniaflavone (compound 10) and 3,8 "-biapigenin (3,8" -biapigenin, compound 11) A health functional food for preventing or ameliorating obesity or diabetes, which comprises at least one compound.
[Chemical Formula 1]

delete The method according to claim 6,
Wherein said compound inhibits the activity of protein tyrosine phosphatase 1B (PTP1B). 2. A health functional food for preventing or ameliorating obesity or diabetes. The method according to claim 6,
Wherein said compound increases glucose uptake. 2. A health functional food for preventing or ameliorating obesity or diabetes. (Selariscinin B, compound 4), selariscinin C (compound 5), selariscinin D (compound 6), and selariscinin E (compound 7) ). &Lt; / RTI &gt;
(2)

Extracting Selaginella tamariscina with water, C1 to C4 lower alcohols or a mixed solvent thereof to prepare a budsons extract; Sequentially fractionating the bamboo shoot extract with dichloromethane, ethyl acetate and n-butanol; And each of the above fractions was chromatographed to obtain the following compounds: selariscinin B, compound 4, selariscinin C, compound 5, selariscinin D, compound 6, (Selariscinin E, compound 7). &Lt; / RTI &gt;
(2)

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