KR20160045980A - Composition for Preventing and Treating Neurodegenerative Diseases Comprising Aurantiamide Acetate - Google Patents

Abstract

The present invention relates to a composition for preventing and treating neurodegenerative diseases comprising aurantiamide acetate as an active ingredient. More particularly, the present invention relates to a composition for preventing and treating neurodegenerative diseases comprising aurantiamide acetate separated from Aspergillus SF-5921 and having an anti-neuritic effect as an active ingredient. The composition for preventing and treating neurodegenerative diseases comprising aurantiamide acetate as an active ingredient according to the present invention is effective for inhibiting production of nitrogen oxides, PGE-2 and IL-1b in the microglia, inhibiting expression of iNOS and COX-2, suppressing activation of NF-κB, reducing IKK α/β/γ phosphorylation level and for reducing JNK and p38 MAPK phosphorylation level, with regard to neuritic responses, and has no cytoxicity. Thus, the composition can be useful for preventing and treating neurodegenerative diseases.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing and treating degenerative neurological diseases containing arsenic amide acetate as an active ingredient, and a composition for preventing and treating neurodegenerative diseases,

The present invention relates to a composition for the prevention and treatment of degenerative neurological diseases containing as an active ingredient arene-amide acetate. More particularly, the present invention relates to a composition for prevention and treatment of degenerative neurological diseases comprising Aspergillus sp. The present invention relates to a composition for the prevention and treatment of degenerative neurological diseases containing alanine amide acetate having an anti-neuronal inflammatory effect isolated from SF-5921.

Neuroinflammation, the chronic inflammation of the brain, causes degenerative neuropathy. The primary immune cells, microglial cells, play an important role in the innate immune response of the central nervous system (Glezer et al., Neuroscience 29: 867-83, 2007; Tremblay et al., J Neurosci 31: 16064-9 , 2011). Microglial cells are macrophages of the brain, which respond to brain damage by inhibiting nitric oxide (NO), prostaglandin E ₂ (PGE ₂ ), MCP-1 (monocyte chemo-attractant protein-1) Including a proinflammatory cytokine such as alpha (TNF-a), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) (Rankine et al., Eur J Neuro Sci 24: 77-86, 2006; Yoon et al., J Biosci Bioeng 107: 429-38, 2009). These cytokines and pro-inflammatory mediators are responsible for apoptosis and brain damage (Boje et al., Brain Res 587: 250-6. 1992; Chao et al., J Immunol 149: 2737-41, 1992). In addition, excessive nitric oxide (NO) may be produced by inducible nitric oxide synthase (iNOS), resulting in neuroinflammatory diseases (Nathan et al., Curr Opin Immunol 3: 65-70, 1991). Clooxygenase-2 (COX-2) can produce several proinflammatory cytokines such as prostaglandin E2 (PGE2) (Chen et al., J Cell Biochem 82: 537-48, 2001). Recent studies have shown that inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), induced by inflammatory stimulants such as LPS and proinflammatory cytokines, (Lappas et al., Biol Reprod 67: 668-73, 2002). Thus, it is possible to modulate the activity of microglial cells to treat neurological disorders such as Alzheimer's disease, Parkinson's disease, HIV-related dementia (HAD), stroke and multiple sclerosis (Good et al., Am J Pathol 149: 21 -8, 1996; Pratico et al., Neurobiol Aging 21: 441, 2000; Hald et al., Exp Neurol 193: 279-90, 2005).

NF-κB (nuclear factor-kappa B) transcription factors are associated with many genes that encode mediators of acute immune and inflammatory responses. NF-κB is a heterodimer of p50-p65 and is a key mediator of the immune response. When NF-κB is inactivated, it binds to IκB and is present in the cytoplasm. However, when IκB-α is phosphorylated in response to an inflammatory signal such as LPS and degraded, it is activated and migrates into the nucleus (Zhang et al., J Clin Invest 107: 13-9, 2001; Ghosh et al., Nat Rev Immunol 8: 837-48, 2008). In addition, mitogen-activated protein kinases (MAPKs) are serine / threonine protein kinases that regulate basic biological responses in response to extracellular stimulation signals. MAPKs are composed of p38, JNK and ERK1 / 2 (p44 / p42), and these molecules play an important role in cell proliferation, differentiation and death (Rao et al., J Leukoc Biol 69: 3-10, 2001 Liu et al., Nat Rev. Immunol 7: 202-12, 2007). NF-κB and MAPKs signaling pathways are involved in the regulation of inflammatory responses, and some studies have shown that natural substances inhibit the NF-κB and MAPKs signaling pathways, resulting in anti-neuroinflammatory effects (Jung et al., Br J Pharmacol 159: 1274-85, 2010).

Conventional degenerative neuropathy treating compositions have become the most serious side effects, and herbal remedies show fewer side effects than other chemotherapeutic drugs. In addition, recent marine microorganisms are promising as a source of pharmacologically active metabolites, and secondary metabolites of marine fungi have been proposed as potential new drug compounds (Fenical et al., Nature Chem Biol 2: 666-73, 2006; Saleem et al., Nat Prod Rep 24: 1142-52, 2007).

Accordingly, the present inventors have made intensive efforts to isolate bioactive natural products from marine microorganisms and to verify their effectiveness. As a result, Aspergillus sp. SF-5921, and confirmed the antinociceptive effect of arene amide acetate on the inflammatory reaction induced by LPS in BV2 microglia, .

It is an object of the present invention to provide a composition for the prevention and treatment of degenerative neurological diseases containing as an active ingredient an aurantiamide acetate.

Another object of the present invention is to provide a food for improving degenerative neurological diseases containing an active ingredient of aurantiamide acetate.

In order to achieve the above object, the present invention provides a composition for preventing and treating degenerative neurological diseases, which comprises an active ingredient of aurantiamide acetate.

The present invention also relates to a process for the preparation of a marine fungus Aspergillus sp. Sp. Containing aurantiamide acetate represented by the following formula (1) A food for improving degenerative neurological diseases containing SF-5921 extract as an active ingredient.

[Chemical Formula 1]

The composition for preventing and treating neurodegenerative degeneracy comprising as an active ingredient the isocyanate according to the present invention is useful for inhibiting nitric oxide, PGE ₂ and IL-1β production, iNOS and COX- 2 expression, suppression of NFκ-B activation, decrease of IKKα / β / γ phosphorylation level, decrease of JNK and p38 MAPK phosphorylation level, and since they are free from cytotoxicity, they can be usefully used as a composition for the prevention and treatment of neurodegenerative diseases .

Figure 1 shows (A) NO, (B) PGE _2, (C) TNF-α induced by pretreatment of BV2 microglial cells with arene amide acetate for 3 hours followed by stimulation with LPS And (D) measuring the concentration of IL-1 [beta], and analyzing the effect of arene-amide acetate.
FIG. 2 shows the results of (A) iNOS and (B) expression of isoenzyme (B) COX-2 protein in BV2 microglia cells pretreated with arene amide acetate for 3 hours and stimulated with LPS The acetate effect was analyzed by Western blot analysis.
Figure 3 shows the results of analysis of the effect of arene amide acetate on the activation of NF-κB induced by LPS. (B) NF-κB binding activity of nuclear extracts by using NF-κB ELISA (Active Motif), (C) determination of IκB-α and Western blot analysis of p-IκB-α and (D) p-IKKα / β / γ and IKK α / β / γ.
Figure 4 shows the results of phosphorylation and protein expression of (A) ERK, (B) JNK and (C) p38 MAPK by pretreating BV2 microglial cells with arene amide acetate for 3 hours followed by stimulation with LPS (500 ng / The results are shown in Western blot analysis.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

In one aspect, the present invention relates to a composition for the prevention and treatment of degenerative neurological diseases containing as an active ingredient, aurantiamide acetate.

The Aurantiamide acetate of the present invention is an Aspergillus sp. As a compound having anti-neuronal inflammatory activity extracted from SF-5921, the aurantiamide acetate has a molecular weight of 445.2127 and is a compound of the molecular formula C ₂₇ H ₂₉ N ₂ O ₄ and has a structure of the formula (1) .

 [Chemical Formula 1]

The neurodegenerative diseases of the present invention are characterized in that they are selected from the group consisting of Alzheimer's disease, Parkinson's disease, HIV-related dementia (HAD), Huntington's disease, Lou Gehrig's disease, Creutzfeldt Jakob disease, stroke and multiple sclerosis.

Compositions containing the compounds of the present invention are characterized by having one or more of the following characteristics.

1) inhibits the production of nitric oxide (NO), prostaglandin E ₂ (PGE ₂ ) and interleukin-1? (IL-1 ?; interleukin-1?);

2) inhibiting the expression of inducible nitric oxide enzyme (iNOS) and cyclooxygenase-2 (COX-2);

3) reduction of the phosphorylation level of IκB-α (inhibitor kappa B-α) and IKK α / β / γ (IκB kinase α / β / γ);

4) inhibit the activation of NF-κB (nuclear factor kappa B); And

5) Reduction of phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK).

The compositions containing the compounds of the invention may additionally comprise suitable carriers, excipients or diluents according to conventional methods.

The composition containing the compound of the present invention may be selected from the group consisting of powders, pills, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, Or < / RTI >

In another aspect of the present invention, there is provided a marine fungus Aspergillus sp. Strain comprising an Aurantiamide acetate represented by the following formula (1) or an Aurantiamide acetate represented by the following formula (1). SF-5921 extract as an active ingredient.

[Chemical Formula 1]

The food of the present invention includes all forms such as functional food, nutritional supplement, health food and food additives. These types of health functional foods can be prepared in various forms according to conventional methods known in the art. For example, as a health food, the isocyanate acetate of the present invention may be prepared in the form of tea, juice, and drink for drinking, granulated, encapsulated, and pulverized. Functional foods also include beverages (including alcoholic beverages), fruits and their processed foods (such as canned fruits, bottled, jam, marmalade, etc.), fish, meat and processed foods such as ham, sausage, (Such as butter, cheese, etc.), edible vegetable oil, margarine, vegetable protein, retort food, fruit juice, fruit juice, Frozen foods, various kinds of seasonings (e.g., soybean paste, soy sauce, sauces, etc.) by adding the isocyanate acetate of the present invention.

The definitions of the main terms used in the description of the present invention and the like are as follows.

As used herein, the term "degenerative neurological disease" refers to a disease that causes degenerative changes in nerve cells of the central nervous system and causes various symptoms, including neuroinflammatory diseases accompanied by neuroinflammation. The congenital degenerative brain diseases according to the present invention include Alzheimer's disease, Parkinson's disease, HIV-related dementia (HAD), Huntington's disease, Lou Gehrig's disease, Creutzfeldt Jakob disease, stroke and multiple sclerosis.

As used herein, the term " inflammation "refers to a defense mechanism of biopsy for a certain stimulus, which is a mechanism of bio-defense to remove injury caused by various harmful stimuli and restore the original state. Irritation of the inflammation, infection, or chemical and physical stimulation, and the process of inflammation can be divided into two types of acute and chronic inflammation. Acute inflammation is a short-term reaction within a few days. Plasma components and blood cells are involved in dephosphorylation by displaying a microcirculatory system. Chronic inflammation has a long duration, and tissue proliferation is seen.

As used herein, the term "nitric oxide" refers to a substance that increases the production amount of nitric oxide synthase upon inducing an intracellular inflammatory reaction. In the nervous system, nitric oxide is synthesized by the nervous system nitric oxide synthase (NOS) present in nerve cells. The synthesized nitric oxide increases the production of cGMP in brain cells, and thereby functions to store externally-recognized information for a long time.

As used herein, "COX-2" is an enzyme involved in the production of prostaglandin, a protein related to an inflammatory reaction. An increase in intracellular COX-2 expression level may be an indicator of progress of the inflammatory reaction.

As used herein, "MAPK " is a major signal transduction system that regulates cell growth and differentiation by transferring the signal from the cell membrane to the nucleus when a growth factor or the like activates a receptor located in the cell membrane.

[Example]

Hereinafter, the present invention will be described in more detail by way of examples. It will be apparent to those skilled in the art that these embodiments are merely illustrative of the present invention and that the technical scope of the present invention is not limited to these embodiments.

Example 1: Isolation and identification of marine fungi

Aspergillus sp. In February 2011, SF-5921 was taken at 375 m below the depth of the Antarctic Ocean (S 76 ° 06.258 ', E 169 ° 12.756'). The 28S rRNA gene of SF-5921 (GenBank accession number KF647561) was identified as Aspergillus penicillioides (U81265), Eurotium chevalieri (JN938915), Aspergillus proliferans (FR848827) and Aspergillus glaucus (JF922029) And 99.87%, 97.94%, 97.81% and 97.81%, respectively. Therefore, it was confirmed that SF-5921 derived from marine fungi was Aspergillus sp., And Aspergillus sp. SF-5921 deposited a strain in the KRRI (Accession No .: KCTC 12614BP).

Example 2 Isolation and Structural Determination of Arenesyamide Acetate

Marine fungi Aspergillus sp. SF-5921 The cells were cultured at 25 DEG C for 14 days in a medium containing 0.4% (w / v) potato starch, 2% (w / v) dextrose, 3% (w / v) NaCl and 1.5% (w / v) Acetate (500 ml) and concentrated in vacuo with 21 mg of the extract. A; (4.2mg, t _R = 33.3min arene upon amide acetate) Ethyl acetate extract to give a concentration gradient for 50 minutes with methanol of 50% to 100%, the fungus metabolite compounds of dipeptide type using reverse phase HPLC Lt; / RTI > The structure of the separated compounds was confirmed by NMR and MS data analysis.

ESIMS data were analyzed using a Q-TOF micro LC-MS / MS instrument (Waters, UK) and optical rotation was recorded using a Jasco p-2000 digital polarimeter. NMR spectra (1D and 2D) were recorded on CDCl ₃ using a JEOL LNM ECP-400 spectrophotometer and chemical shifts were based on the peak of the residual solvent (δ _H / δ _C = 7.26 / 77.0). The HSQC and HMBC experiments were optimized to ¹ J _CH = 140 Hz and ⁿ J _CH = 8 Hz. The HPLC (YOUNGLIN-YL9100, Korea) separation was performed at a rate of 5 mL / min using a Phenomenex Synergi 4u Polar-RP 80A, AXIA packed column (21.2 × 150 mm, 5-mm particle size).

Analysis of the NMR structure of the arenediamide acetate isolated in this Example: white powder, [?] _D 44 ° ( c 0.075, CH ₂ Cl ₂ ); ^{1 H-NMR (400MHz, CDCl} 3): δ7.71 (2H, d, J = 7.7Hz, H-16 / H-20), 7.52 (1H, t, J = 7.7Hz, H-18), 7.43 (2H, t, J = 7.7Hz , H-17 / H-19), 7.28 (2H, d, J = 7.0Hz, H-23 / H-27), 7.26 (2H, d, J = 7.0Hz, H-24), 7.23 (1H, d, J = 5.6 Hz, H-25), 7.16 (2H, brs, H-5 / , 7.06 (2H, d, J = 6.9Hz, H-6 / H-8), 6.74 (1H, d, J = 7.7Hz, N-Hb), 5.94 (1H, d, J = 8.4 Hz, N- Ha), 4.75 (1H, q , J = 5.5Hz, H-13), 4.34 (1H, m, H-2), 3.92 (1H, dd, J = 11.6, 4.8Hz, H-10b), 3.80 ( 1H, dd, J = 11.3, 4.0Hz, H-10a), 3.22 (1H, dd, J = 13.7, 5.5Hz, H-21b), 3.05 (1H, dd, J = 13.6, 8.4 Hz, H-21a ), 2.75 (1H, dd, J = 11.8, 1.8 Hz, H-3b), 2.72 (1H, s, H-3a), 2.02 (3H, s, H-12); ¹³ C-NMR (100 MHz, CDCl ₃ )?: 170.9 (C-11), 170.3 (C-1), 167.2 (C-14), 137.8 C-24), 128.9 (C-6 / C-8), 128.7 (C-5 / C-9), 128.6 (C-17 / C-19), 127.2 (C-25), 127.1 C-13), 49.5 (C-2), 38.5 (C-21), 37.5 (C-3), 20.9 (C-12); HRESIMS: m / z 445.2122 [M + H] ⁺ (calcd for C ₂₇ H ₂₉ N ₂ O ₄ , 445.2127).

[Chemical Formula 1]

Example 3: Determination of cytotoxicity of arene amide acetate

In this example, the effect of arene amide acetate on cytotoxicity was confirmed in BV2 microglia using MTT assay.

BV2 microglial cells 5x10 ^{5 /} mL penicillin G (100U / ml), streptomycin (100mg / ml), with a containing L- glutamine (2mM) and the FBS (10%) inactivated by heat DMEM (Gibco BRL Co. , USA) at 37 ° C and 5% CO ₂ . To measure cytotoxicity, 1 mL of 100 mg / mL MTT was treated for 4 hours in 5x10 ⁵ / mL cells in a 96-well plate and the absorbance at 590 nm was measured.

As a result, no cytotoxicity was observed at a concentration of 10 μM to 200 μM of isocyanate acetate, and a concentration in the range of 10 μM to 100 μM of isocyanate acetate was used in the examples.

Example 4: Influence on the proinflammatory mediators and cytokine production of areenamide acetates

Concentrations of proinflammatory mediators such as NO and PGE ₂ were measured in order to determine the antinociceptive effect of arene amide acetate on BV2 microglia stimulated with LPS. The production of NO was measured by analyzing the concentration of nitrate by the Griess reaction. 100 liters of sample and Griess reagent (Solution A: 222488; Solution B: S438081, Sigma) were mixed in equal amounts and measured at 525 nm by ELISA. In addition, PGE ₂ , TNF-α and IL-1β were pretreated with isoleucine acetate in a 24-well plate for 3 hours, stimulated with LPS (1 μg / ml) for 12 hours, (R & D Systems, USA).

BV2 microglia cells pretreated with arene amide acetate for 3 hours and then stimulated with LPS (1 / / mL) for 24 hours, as shown in Fig. 1, LPS increased the concentration of nitrate by about 10 times . However, the BV2 microglia pretreated with arene amide acetate showed a concentration-dependent decrease in NO production, and an IC ₅₀ of 49.70 μM (FIG. 1A). The isocyanate acetate also reduced PGE ₂ production in a concentration dependent manner, with an IC ₅₀ of 51.53 μM (FIG. 1B). Further measurement of the levels of pro-inflammatory cytokines TNF-α and IL-1β revealed that the IC ₅₀ of IL-1β was 40.36 μM, which was dependent on the concentration of the isocyanate acetate (FIG. 1D) (Fig. 1C).

Example 5: Effect of arene amide acetate on iNOS and COX-2 protein expression

The effect of arene-amide acetate on iNOS and COX-2 protein expression in BV2 microglia cells stimulated with LPS was confirmed using Western blot (Fig. 2). Western blot was prepared by pretreating with isoleucine amide acetate and BV2 microglia stimulated with LPS were incubated with lime containing protease inhibitor (0.1 mM PMSF, 5 mg / mL aprotinin, 5 mg / mL pepstatin A and 1 mg / mL chymostatin) Proteins were extracted using cis buffer (20 mM Tris-HCl, pH 7.4). Protein concentration was measured with a Lowry protein assay kit (P5626; Sigma) and protein expression was analyzed using an ECL kit (Amersham).

As a result, LPS-induced iNOS and COX-2 protein expression was inhibited (FIG. 2A, B) depending on the concentration of alanine amide acetate, suggesting that isocyanate acetate reduced iNOS and COX-2 protein expression Lt; RTI ID = 0.0 > proinflammatory < / RTI > cytokines and mediators.

Example 6: Effect of arene amide acetate on IκB-α phosphorylation and NF-κB activity

NF-κB is a major regulator of inflammatory responses mediated by LPS or proinflammatory cytokines. The iNOS and COX-2 promoters include the NF-κB site that can induce gene expression (Rajapakse et al., Immunology 123: 348-57, 2008; Karin et al., Annu Rev Immuno 29: 72-9 , 2004). Thus, in this example, the regulation of NF-κB pathway by isocyanamide acetate was investigated.

BV2 microglia cells were pretreated with areenamide acetate for 3 hours and then stimulated with LPS (1 μg / mL) for 30 minutes. Cellular and nuclear extracts were homogenized in PRE-mammalian protein extraction buffer (1:20, w: v) (Pierce Biotechnology, USA) containing 1 mM PMSF and protease inhibitor cocktail I (EMD Biosciences, USA) Nuclear and cytoplasmic extraction reagents (Pierce Biotechnology, USA). Subsequently, the DNA binding activity of NF-κB was measured using a TransAM kit (Active Motif, USA) using nuclear extracts.

As a result, migration of p65 and p50 to the nucleus was increased in the cells stimulated with LPS, but migration to the nucleus was significantly inhibited in the cells pretreated with arene amide acetate (Fig. 3A). In addition, IκB-α phosphorylation was increased by LPS stimulation, but IκB-α phosphorylation was markedly reduced and IκB-α degradation was also inhibited in the cells pretreated with areneamide acetate (FIG. 3C). As can be seen in FIG. 3B, the DNA binding activity of NF-κB is increased about 3-fold by LPS treatment, but the isocyanate acetate inhibits activity in a concentration-dependent manner. Thus, it was confirmed that the isoamyl acetate inhibits DNA binding of NF-κB through inhibition of migration of p65 / p50 to the nucleus due to IκB-α phosphorylation and degradation.

Since IκB-α phosphorylation is known to be involved in IKK (IκB kinase) (Yamamoto et al., Trends Biochem Sci 29: 72-9, 2004), the activity of IKK // induced by LPS . As can be seen in Figure 3D, LPS induces phosphorylation of IKK [alpha] / [beta] / [gamma]. However, pretreatment with 50 or 100 μM areocyanate acetate has no effect on total intracellular IKK α / β / γ levels, but IKK α / β / γ phosphorylation is significantly reduced. As a result, it was confirmed that the isoleucine amide acetate inhibits LPS-induced NF-kB activity through inhibition of the activity of the IKK complex.

Example 7: Influence of alanine amide acetate on phosphorylation of MAPK

The MAPK pathway is involved in the inflammatory response, and inhibition of the MAPK pathway is an important route to prevent the induction of proinflammatory mediators by LPS. Thus, the MAPK family of ERK, JNK and p38 are major targets of anti-inflammatory drug development in controlling inflammatory responses (Reibman et al., J Immunol 165: 1618-25, 2000; Kaminska et al., Biochem Biophys Acta 1754: 62, 2005).

In this example, the effect of arene amide acetate on ERK, JNK and p38 phosphorylation induced by LPS was examined in BV2 microglia, and how alanic amide acetate inhibited the inflammatory response in the MAPK pathway.

As a result, ERK, JNK and p38 phosphorylation were increased 30 minutes after the LPS treatment, but it was confirmed that the cells pretreated with 10-100 μM arene amide acetate for 3 hours showed a concentration-dependent decrease in JNK and p38 phosphorylation (FIG. 4B, C ). However, there was no effect on ERK phosphorylation (Fig. 4A), and the degree of expression of ERK, JNK and p38 was not altered by isoleucamide acetate as well as LPS (Fig. 4). This indicates that the isocyanate acetates inhibit the JNK and p38 MAPK signaling pathways and regulate the inflammatory response.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Korea Biotechnology Research Institute KCTC12614BP 20140625

Claims (8)

A composition for preventing and treating degenerative neurological diseases containing as an active ingredient aurantiamide acetate.
The composition of claim 1, wherein the aurantiamide acetate has the structure of Formula 1:
[Chemical Formula 1]

2. The composition of claim 1, wherein the aurantiamide acetate has anti-neuronal inflammatory activity.
The method of claim 1, wherein the aurantiamide acetate is selected from the group consisting of marine fungi Aspergillus sp. SF-5921. ≪ / RTI >
The composition of claim 1, wherein the degenerative neurological disease is selected from the group consisting of Alzheimer's disease, Parkinson's disease, HIV-associated dementia (HAD), Huntington's disease, Lou Gehrig's disease, Creutzfeldt Jakob disease, stroke and multiple sclerosis .
4. The composition according to any one of claims 1 to 3, having one or more of the following properties:
1) inhibits the production of nitric oxide (NO), prostaglandin E ₂ (PGE ₂ ) and interleukin-1? (IL-1 ?; interleukin-1?);
2) inhibiting the expression of inducible nitric oxide enzyme (iNOS) and cyclooxygenase-2 (COX-2);
3) reduction of phosphorylation levels of IκB-α (inhibitor kappa B-α) and IKK α / β / γ (IB kinase α / β / γ);
4) inhibit the activation of NF-κB (nuclear factor kappa B); And
5) Reduction of phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK).
The composition of claim 1, further comprising a pharmaceutically acceptable carrier, excipient or diluent.
A marine fungus Aspergillus sp. Containing an Aurantiamide acetate represented by the following formula (1) or an Aurantiamide acetate represented by the following formula (1). SF-5921 Extract is an effective ingredient for the treatment of degenerative neurological diseases.
[Chemical Formula 1]

Images