KR102008722B1 - Anti-inflammatory peptide Scolopendrasin-9 derived from Scolopendra subspinipes mutilans, composition comprising it for the treatment of sepsis - Google Patents

Abstract

The present invention relates to an anti-inflammatory peptide Scollofendracin-9 derived from Scolopendra subspinipes mutilans , an anti-inflammatory composition comprising the same as an active ingredient or a composition for treating sepsis. Scolofendracin-9 peptide is effective in controlling various inflammatory reactions such as inhibiting the production of tumor necrosis factor-α (TNF-α) or IL-6 (interleukin-6). It can be easily used as a composition for the treatment of various inflammatory diseases such as.

Description

Anti-inflammatory peptide Scolopendrasin-9 derived from Scolopendra subspinipes mutilans, composition comprising it for the treatment of sepsis}

The present invention relates to an anti-inflammatory peptide Scollofendracin-9 derived from Scolopendra subspinipes mutilans , an anti-inflammatory composition comprising the same as an active ingredient or a composition for treating sepsis.

Inflammation is one of the defenses of biological tissues against certain stimuli. It is a complex lesion that involves three things: tissue degeneration, circulatory disorders and exudates, and tissue proliferation. The cause is due to mechanical injury, physical factors such as temperature, radiation, chemical factors such as poisons, parasites such as bacterial infection, etc., and most of them are caused by bacteria. In addition to these main causes, the occurrence is complicated by various concomitant factors and predisposition or immunity of the individual.

Inflammatory response is also one of the most important pathological mechanisms in response to the host's defense mechanism against wounds, microbial infections. Macrophages are the most representative immune cells that control this inflammatory response. Activated macrophages are tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO). ) And various inflammatory mediators such as reactive oxygen species (ROS) (Laskin, DL et al., 2011). On the other hand, overexpression of these inflammatory mediators leads to rheumatoid arthritis, osteoporosis, sepsis, vascular disease, cancer and the like (Lawrence, T. et al., 2012).

Sepsis is a condition in which systemic symptoms such as high fever, joint pain, headache, and malaise are accompanied by chills caused by microorganisms or toxins produced by microorganisms such as Pseudomonas aeruginosa, Escherichia coli, streptococci, staphylococci, and pneumococci. Say. Severe symptoms are accompanied by hypotension, decreased urine volume and septic shock (Nat. Med. 2003, 9, 517-524). Although the path of infection of microorganisms is unknown, appendicitis, otitis media, dermatitis, pressure sores, pulmonary diseases, cholecystitis, pyelitis, and osteomyelitis are known as causative agents of sepsis. Sepsis can be diagnosed through blood tests, urine tests, and cerebrospinal fluid tests. Also, an increase in white blood cell count and acute inflammatory substances can help diagnose sepsis.

So far, no fundamental treatment for the treatment of sepsis has been identified. Sepsis is not as good as conventional anti-inflammatory treatments, and even the only FDA-approved drotrecogin alfa, Xigris, Engl. J. Med. 2012, 366, 2055-2064 has been developed for sepsis at clinical stage. Because the effect of treatment is not clear, studies on this have been discontinued. Currently, sepsis is usually treated with antibiotics or antifungal injections, and the medication and duration of treatment depends on the type of microorganism. Hemodialysis or transfusion may also be given depending on the patient's condition. If antibiotics and antifungal medications are heard well, sepsis can be cured, but it can be difficult to treat in people who are infected with drug-resistant microorganisms, in patients with weak immunity, or when treatment is started too late. In addition, the mortality rate of sepsis is very high, reaching 50-70%, and is known to be the leading cause of death worldwide (Nat. Med. 2003, 9, 517-524). Complications of sepsis can lead to sequelae. Complications include meningitis, neurologic sequelae, and purulent arthritis, combined with abnormal bone growth.

The inventors of the present invention, while studying various physiological activities using peptides derived from Scolopendra subspinipes mutilans , confirmed that the novel peptide scolofendracin -9 has anti-inflammatory effect and treatment effect of sepsis. Lofendracin-9 peptide was found to be readily available as a therapeutic agent that can inhibit various inflammatory reactions to complete the present invention.

Korean Patent Registration No. 10-1700603 (Invention: Antimicrobial Peptide Perilinettacin-1 Derived from Cockroach and Its Composition, Applicant: Korea, Registered Date: Jan. 23, 2017) Korean Registered Patent No. 10-1697179 (Invention name: Composition for the prevention and treatment of atopic dermatitis, including Scolopefendracin-1 peptide as an active ingredient, Applicant: Korea, Registered date: January 11, 2017) Korean Registered Patent No. 10-1625502 (Invention: Novel Scolopendracin-4 Peptide and Composition thereof Promoting the Growth of Colonic Epithelial Cells, Applicant: Korea, Registered Date: May 24, 2016)

Lawrence, T. et al., Anti-inflammatory lipid mediators and insights into the resolution of inflammation, Nat. Rev. Immunol., 2002, 2, 787-795. Riedemann, N. C. et al., Novel strategies for the treatment of sepsis., Nat. Med. 2003, 9, 517-524. Ranieri, V. M. et al., Drotrecogin alfa (activated) in adults with septic shock., Engl. J. Med. 2012, 366, 2055-2064.

Disclosure of Invention An object of the present invention is to provide an anti-inflammatory peptide scolofendracin-9 derived from Scolopendra subspinipes mutilans , an anti-inflammatory composition comprising the same as an active ingredient, or a composition for treating sepsis.

The present invention relates to a peptide represented by the following SEQ ID NO: 1 synthesized in the gene of anti-inflammatory peptide isolated from Scolopendra subspinipes mutilans .

SEQ ID NO: 1: MCKYFIKIVSKSAKK-NH ₂

The peptide is characterized in that it is effective in inhibiting the production of inflammatory cytokines of tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6).

Accordingly, the present invention provides an anti-inflammatory composition comprising the peptide as an active ingredient, and provides a composition for preventing or treating sepsis comprising the same.

Therefore, the present invention can provide a health functional food for prevention or improvement of sepsis containing the peptide as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention relates to a peptide represented by SEQ ID NO: 1 synthesized from a gene of anti-inflammatory peptide isolated from Scolopendra subspinipes mutilans . Therefore, the present invention may be directed to an anti-inflammatory peptide directly isolated from Scolopendra subspinipes mutilans having the same sequence as SEQ ID NO: 1.

Therefore, the present invention may be directed to an anti-inflammatory peptide directly isolated from Scolopendra subspinipes mutilans having the same sequence as SEQ ID NO: 1.

The peptide of the present invention may have a carboxyl terminus of -NH ₂ form or -OH form.

In the present invention, in order to identify the peptide gene derived from Scolopendra subspinipes mutilans , first, the freeze is rapidly frozen with liquid nitrogen to separate the total RNA, and the RNA information is determined using RNA seq analysis to determine the genetic information on the royal transcripts. Based on the sequence of amino acids (peptides) translated from the respective transcripts, unigenes estimated to be peptides exhibiting anti-inflammatory activity may be selected using properties of existing anti-inflammatory peptides.

The amino acid sequence of the peptide consists of 15 amino acids, MCKYFIKIVSKSAKK-NH ₂ , which is named Scolopendrasin-9.

The present invention also provides an anti-inflammatory composition comprising the peptide as an active ingredient, a pharmaceutical composition for the prevention or treatment of sepsis.

More specifically, the pharmaceutical composition of the present invention may be administered to various mammals such as rats, livestock, humans, and the like. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections.

Pharmaceutical compositions containing the scolofendracin-9 peptide of the present invention can also be administered parenterally during clinical administration and can be used in the form of general pharmaceutical formulations. The peptide or the composition containing the same may be administered in various parenteral dosage forms, and when formulated, it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. which are commonly used. Can be. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As a suppository base, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

In addition, the scolofendracin-9 peptide of the present invention can be used in admixture with various carriers accepted as a medicament, such as physiological saline or organic solvent, and in order to increase stability or absorption, glucose, sucrose or dex Carbohydrates such as tran, ascorbic acid or antioxidants such as glutathione, chelating agents, small molecule proteins or other stabilizers can be used as medicaments.

In the pharmaceutical composition, the total effective amount of the scolofendracin-9 peptide of the present invention or a peptide having more than 95% homology therewith may be determined in a single dose (eg, by bolus form or by infusion for a relatively short period of time). It can be administered to a patient in a single dose, and multiple doses can be administered by a fractionated treatment protocol that is administered for a long time. Since the concentration is determined by taking into consideration the various factors such as the age and health of the patient as well as the route and frequency of administration of the pharmaceutical composition, in view of the above, it will be appreciated by those skilled in the art. Appropriate effective dosages for particular uses as pharmaceutical compositions containing the novel peptides of the invention may be determined.

The present invention can provide a health functional food for prevention or improvement of sepsis containing the peptide as an active ingredient. The health functional food may include food supplements acceptable food supplements. The health functional food of the present invention includes the form of tablets, capsules, pills, or liquids, and the food to which the extract of the present invention can be added includes, for example, various drinks, meats, sausages, breads, candy, Snacks, noodles, ice cream, dairy products, soups, ionic drinks, beverages, alcoholic beverages, gum, tea and vitamin complexes.

The present invention relates to an anti-inflammatory peptide Scollofendracin-9 derived from Scolopendra subspinipes mutilans , an anti-inflammatory composition comprising the same as an active ingredient or a composition for treating sepsis. Scolofendracin-9 peptide is effective in controlling various inflammatory reactions such as inhibiting the production of tumor necrosis factor-α (TNF-α) or IL-6 (interleukin-6). It can be used easily as a therapeutic composition of.

Figure 1 shows the results of the reaction of the present invention scolofendracin-9 peptide in the calcium neutrophil cells and cell migration in neutrophils.
Figure 2 shows the results of the reaction of calcium ion free and cell migration in the vector-, FPR1- or FPR2-expressing RBL-2H3 cells of the scolofendracin-9 peptide of the present invention. 2A shows the results of Vector-, FPR1- or FPR2-expressing RBL-2H3 cells sequentially from top to bottom.
Figure 3 shows the results confirming that the scolofendracin-9 peptide of the present invention has the effect of inhibiting the expression of inflammatory cytokines in mouse neutrophil cells.
4 shows the results confirming that the scolofendracin-9 peptide of the present invention has a degranulation release control effect and a reactive oxygen production effect in mouse neutrophil cells.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.

Example 1 Selection of Anti-Inflammatory Peptide Gene from Wang Zhi>

In order to identify the peptide genes showing biological activity from Wangi-ni, Wangi-ni was rapidly frozen with liquid nitrogen to isolate the whole RNA, and the RNA information was used to confirm the genetic information of Wangi-ri transcripts using RNA seq analysis. Based on the amino acid sequence translated from the filtration of the entire unijin by referring to the properties of the existing biologically active peptides, the resulting genes were selected as a new biologically active peptide. The selected amino acid sequence was MCKYFIKIVSKSAKK-NH ₂ and consisted of 18 amino acids and named Scolopendrasin-9 (Table 1).

Peptide Amino acid sequence Scolopendrasin-9 MCKYFIKIVSKSAKK-NH ₂

<Example 2. Scolofendracin-9 Synthesis and Separation Purification>

Scolofendracin-9 peptide derived from Wangzine identified in Example 1 was synthesized and purified.

First, in order to synthesize the scolofendracin-9 peptide, the inventors of the present invention, the liquid phase solidification method of Merrifield (Merrifield, RB., J. Am. Chem. Soc., 85, using a Fmoc amino group protective container) 2149, 1963) to prepare peptides.

The peptide synthesis method was synthesized by a solid phase method using Fmoc (9-fluorenylmethoxycarbonyl) as a protecting group of the N _α -amino group of amino acids.

Specifically, the peptide having the carboxyl terminus of -NH ₂ form Rink Amide MBHA-Resin as the starting material, and the peptide of the carboxyl terminus -OH form was used as the starting material Fmoc-amino acid-Wang Resin.

Elongation of peptide chains by coupling of Fmoc-amino acids was carried out by DCC ( N -hydroxybenzo-triazole (HOBt) -dicyclo-hexylcar-bodiimide) method.

After coupling the Fmoc-amino acid at the amino terminus of each peptide, the Fmoc group was removed with 20% piperidine / N-methylpyrrolidone (NMP) solution, washed several times with NMP and dichloromethane (DCM), and then nitrogen. Dried with gas.

Trifluoroacetic acid (TFA) -phenol-thioanisole-H ₂ O-triisopropylsilane (85: 5: 5: 2.5: 2.5, vol./vol.) Solution was added thereto and reacted for 3 hours to remove the protecting group and the resin. The peptide was isolated and then the peptide was precipitated with diethyl ether. The crude peptide thus obtained was subjected to a purified reverse phase-HPLC column (Delta Pak, C ₁₈ 300 μs, 15 μm, 19.0 mm x) with an acetonitrile gradient containing 0.1% TFA. 30mm, Waters).

The synthetic peptide was hydrolyzed with 6 N-HCl at 110 ° C. for 24 hours, and the residue thus obtained was concentrated under reduced pressure, dissolved in 0.02 N-HCl, and the amino acid composition was measured by an amino acid analyzer (Hitachi 8500 A).

In addition, the molecular weight was calculated based on the sequence of the synthesized peptide, and the exact molecular weight was measured using a matrix-assisted laser desorption ionization mass spectrometer.

As a result, it was confirmed that the antimicrobial peptide having the correct amino acid sequence was synthesized because the measured molecular weight and the calculated molecular weight coincide.

In addition, the WKYMVm, MMK-1, and WRWWWW (WRW4) peptides used as FPR2 agonists in the present invention were synthesized in the same manner. Lysphosphatidylserine (LPS) was purchased from Avanti Polar Lipids, and fMLF (FPR1 agonist) was purchased from Sigma.

Example 3 Preparation of Experimental Cells

Example 3-1. Isolation of Mouse Neutrophils

Mouse bone marrow neutrophils were isolated according to previous reports. In more detail, the following method was performed. Mouse bone marrow cells isolated from femur and tibia were suspended in HBSS-EDTA solution. After centrifugation at 400g for 10 minutes, the resuspended cells were carefully loaded with 52% / 69% / 78% Percoll gradient and centrifuged at 1500g for 30 minutes. Cells were separated from the 69% / 78% interface layer and red blood cells were removed by hypotonic lysis. The isolated cells were analyzed by flow cytometry (BD FACSCanto II) and were identified as more than 95% Ly6G positive, indicating that the neutrophils were well separated.

Example 3-2. Vector-, FPR1- or FPR2-expressing RBL-2H3 Cells

FPR1- or FPR2- gene-expressing cell lines were prepared using RBL-2H3 cells, basophilic leukemia cells (preparation of vector-RBL-2H3 cell line as a control). The construction of the cell line is described in J Immunol. 2000 Oct 15; 165 (8): 4598-4605.

<Example 4. Confirmation of calcium ion concentration and cell migration in neutrophils>

Activation of immune cells, including neutrophils, in many cases involves an increase in intracellular calcium ions. Increasing intracellular calcium ions can mediate various physiological functions such as cell mobility control, proliferation control, and inflammation control. Neutrophils are immune cells that first move to the infection site and initiate an innate immune response upon invasion of the infecting organism, and thus, the activation of neutrophils involves the release of calcium ions in the cells. Therefore, since the anti-inflammatory effect of Scolopendrasin-9 of the present invention can be confirmed by confirming the calcium ion reaction in neutrophils, it was examined whether calcium ion in neutrophils was liberated.

LPS used in the experiments below stimulates RBL-2H3 used to express FPR1- or FPR2 to increase intracellular calcium ions. fMLF is an agonist that selectively acts only on FPR1 and not on FPR2. MMK-1, on the other hand, is an agonist that selectively acts only on FPR2 and not on FPR1. WKYMVm is an agonist that acts on both FPR1 and FPR2.

To this end, intracellular calcium levels were measured by Grynkiewicz's method using fura-2 / AM (Fura-2 pentaacetoxymethylester). In more detail, the following method was performed. 3 μM fura-2 / AM was loaded onto mouse neutrophils in fresh serum-free RPMI 1640 medium and reacted at 37 ° C. for 50 minutes. Cells loaded with Fura-2 / AM (1 × 10 ⁷ ) were placed in a lock solution (154 mM NaCl, 5.6 mM KCl, 1.2 mM MgCl ₂ , 5 mM HEPES [4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid], pH 7.3 , 10 mM glucose, 2 mM CaCl ₂ , and 0.2 mM EGTA [Ethylene Glycol Tetraacetic Acid]. After stimulating the cells with 100 μg / ml of Scolopendrasin-9 and 1 μM of WKYMVm, the reaction occurred immediately after stimulating the cells. Fluorescence changes were measured at dual excitation wavelengths of 340 nm and 380 nm and emission wavelengths of 500 nm. .

As a result, it was confirmed that calcium ion glass in neutrophils was induced by the concentration of 100 μg / ml of Scolopendrasin-9 (FIG. 1A).

Neutrophil mobility is a key process for initiating an immune response in infectious diseases and inflammatory diseases. We investigated whether neutrophil mobility is promoted by Scolopendrasin-9.

Mobility for mouse bone marrow neutrophils was confirmed by chemotaxis analysis and performed according to previous reports using a multiwell Boyden chamber. The isolated cells were applied to a polycarbonate filter (mouse neutrophil pore size 3 μm, RBL-2H3 cells pore size 8 μm) for 90 minutes at 37 ° C. (4 hours for RBL-2H3 cells). The migrated cells were stained with hematoxylin (Sigma, St. Louis, Mo., USA) and counted using an optical microscope as reported. At this time, Scolopendrasin-9 and WKYMVm were treated with Scolopendrasin-9 at 1-100 μg / ml and WKYMVm 1 μM at 37 ° C. for 90 minutes.

As a result, it was confirmed that the mobility of neutrophils is promoted at a concentration of Scolopendrasin-9 1-100 µg / ml (FIG. 1B).

<Example 5. Confirmation of calcium ion free regulatory effect and mobility in immune cells by confirming formyl peptide receptor 2 function>

Formyl peptide receptor (FPR) is one of several receptors that regulate chemotaxis of neutrophils. Calcium ion status in neutrophils was confirmed by FPR sub-signal through Scolopendrasin-9 treatment.

To this end, Scolopendrasin-9 was reacted with vector-, FPR1 and FPR2-expressing RBL-2H3 cell lines instead of neutrophils isolated from mice, and calcium concentration was measured in the same manner as in Example 4, and is shown in FIG. 2A (top to bottom). Sequentially Vector-, FPR1- or FPR2-expressing RBL-2H3 cells). At this time, 1 µM of LPS, 1 µM of fMLF, and 1 µM of MMK-1 were simultaneously reacted according to the treatment groups.

Referring to FIG. 2A, the change of calcium ion is selectively confirmed only in the FPR2-expressing RBL-2H3 cell line upon treatment with Scolopendrasin-9.

Similarly, in order to test whether Scolopendrasin-9 can directly induce chemotaxis of neutrophils via FPR2, Scolopendrasin-9 was reacted by the method of Example 4 to the vector- and FPR2-expressing RBL-2H3 cell lines to confirm cell mobility. It is shown in Figure 2B.

Referring to Figure 2B, it can be seen that the mobility of the cells at the concentration of 5 ~ 50㎍ / ㎖ Scolopendrasin-9 in the FPR2-expressing RBL-2H3 cell line is promoted.

<Example 6. Confirmation of cytokine production regulation effect in neutrophils>

In order to confirm the cytokine production regulation effect in neutrophils, the experiment was conducted by Enzyme Linked Immunosorbent Assay (ELISA) method. Mouse neutrophils (5x10 ⁵ ) in 2% serum RPMI 1640 medium were treated with Scolopendrasin-9 1-100 μg / ml, and after 30 minutes in the LPS treatment group, the supernatants were treated with 1 μg / ml LPS. It was used for the experiment. First, the capture antibody of cytokines to be used in the ELISA plate is attached overnight, and then the supernatant obtained from the neutrophils is added to the reaction. Biotin-bound cytokine detection antibody, avidin-HRP, and substrate solution were treated in this order and the reaction was stopped with acidic solution and measured at OD 450nm with spectrophotometer.

In infectious and inflammatory diseases, neutrophils are activated by external stimuli to produce various types of cytokines that regulate the activity of other cells around them. In order to confirm that cytokine production is promoted in mouse neutrophils by treatment with scolopendrasin-9, the cytokine production of CCL2, IL-6, TNF-α, etc. was confirmed by ELISA method in neutrophils of LPS treated / non-treated groups, respectively. 3 is shown.

LPS (Lipopolysaccharide) is a substance that stimulates neutrophils to produce various kinds of cytokines and mediates the inflammatory response. Referring to FIG. It was confirmed that cytokines such as IL-6, TNF-α, and CCL2 were reduced upon Scolopendrasin-9 treatment.

<Example 7. Confirmation effect of degranulation release amount and reactive oxygen production effect of neutrophils>

In order to observe the degranulation of neutrophils, the degree of degranulation was measured by beta-hexosaminidase assay. Neutrophils (1x10 ⁷ / ml) were dissolved in Tyrode solution (137 mM NaCl, 12 mM NaHCO ₃ , 5.6 mM glucose, 2.7 mM KCl, 1 mM CaCl ₂ , 0.5 mM MgCl ₂ , 0.4 mM NaH ₂ PO ₄ , 0.1 g / 100 ml BSA, 25 mM HEPES , pH7.4) After dispensing Scolopendrasin-9 1 ~ 100㎍ / ㎖ or WKYMVm 1μM to the cells and reacted for 30 minutes at 37 ℃, 5% CO ₂ conditions. The supernatant and the cells are separated and dissolved in a cell lysis solution (0.6% Triton X-100 in PBS). Substrate solution (5mM p-nitrophenyl-N-acetyl-β-D-glucosamindide in 0.1M citrate buffer (pH 3.8)) to each supernatant and cells, and reacted for 2 hours at 37 ℃, 5% CO ₂ conditions. The reaction was stopped with 0.4 M Na ₂ CO ₃ solution and measured at 405 nm with an OD spectrophotometer.

Immune cells that produce inflammatory mediators and store them in granules cause degranulation release when activated by an inflammatory response. Degranulation release of neutrophils by Scolopendrasin-9 was confirmed in Figure 4A. Referring to FIG. 4A, it was confirmed that the amount of degranulation released from neutrophils treated with Scolopendrasin-9 1-100 μg / ml was significantly increased.

Superoxide anion production was measured by cytochrome c reduction assay to confirm the effect of reactive oxygen production, an important function of neutrophils. To this end, cytochrome c reduction assays were measured using a microtiter 96-well plate ELISA reader (Bio-Tek instruments, EL312e, Winooski, VT, USA). Isolated mouse neutrophils (1 × 10 ⁶ cells / 96 well plates, 100 μl RPMI 1640 medium per well) were stimulated with Scolopendrasin-9 1-50 μg / ml or WKYMVm 1 μM in the presence of 50 μM cytochrome c and 5 μM cytochalasin B. . Superoxide production was measured over 10 minutes at 550 nm for 1 minute to confirm the change in light absorption. The results are shown in FIG. 4B (the lower figure of FIG. .

<110> REPUBLIC OF KOREA (MANAGEMENT: RURAL DEVELOPMENT ADMINISTRATION) <120> Anti-inflammatory peptide Scolopendrasin-9 derived from          Scolopendra subspinipes mutilans, composition comprising it for          the treatment of sepsis <130> 261 <160> 1 <170> KoPatentIn 3.0 <210> 1 <211> 15 <212> PRT <213> Unknown <220> <223> Scolopendra subspinipes mutilans <400> 1 Met Cys Lys Tyr Phe Ile Lys Ile Val Ser Lys Ser Ala Lys Lys   1 5 10 15

Claims (5)

Peptide consisting of the amino acid sequence of SEQ ID NO: 1 from Scolopendra subspinipes mutilans , the effect of inhibiting the production of inflammatory cytokines of tumor necrosis factor-α (TNF-α) or IL-6 (interleukin-6) Anti-inflammatory and anti-septic peptides.
SEQ ID NO: 1: MCKYFIKIVSKSAKK-NH ₂ delete An anti-inflammatory composition comprising the peptide of claim 1 as an active ingredient. A composition for the prevention or treatment of sepsis, comprising the peptide of claim 1 as an active ingredient. Health functional food for the prevention or improvement of inflammatory diseases comprising the peptide of claim 1 as an active ingredient.

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