KR20200027769A - Composition for improvement, treatment or prevention of inflammatory diseases containing asaronic acid - Google Patents
Composition for improvement, treatment or prevention of inflammatory diseases containing asaronic acid Download PDFInfo
- Publication number
- KR20200027769A KR20200027769A KR1020180105993A KR20180105993A KR20200027769A KR 20200027769 A KR20200027769 A KR 20200027769A KR 1020180105993 A KR1020180105993 A KR 1020180105993A KR 20180105993 A KR20180105993 A KR 20180105993A KR 20200027769 A KR20200027769 A KR 20200027769A
- Authority
- KR
- South Korea
- Prior art keywords
- asaronic acid
- macrophages
- acid
- asaronic
- composition
- Prior art date
Links
- KVZUCOGWKYOPID-UHFFFAOYSA-N 2,4,5-Trimethoxybenzoic acid Chemical compound COC1=CC(OC)=C(C(O)=O)C=C1OC KVZUCOGWKYOPID-UHFFFAOYSA-N 0.000 title claims abstract description 137
- 239000000203 mixture Substances 0.000 title claims abstract description 27
- 230000002265 prevention Effects 0.000 title claims description 11
- 208000027866 inflammatory disease Diseases 0.000 title abstract description 10
- 230000006872 improvement Effects 0.000 title description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 235000013305 food Nutrition 0.000 claims abstract description 20
- 239000004480 active ingredient Substances 0.000 claims description 20
- 206010061218 Inflammation Diseases 0.000 claims description 15
- 230000004054 inflammatory process Effects 0.000 claims description 15
- 208000008589 Obesity Diseases 0.000 claims description 13
- 235000020824 obesity Nutrition 0.000 claims description 13
- 206010012601 diabetes mellitus Diseases 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims 1
- 210000002540 macrophage Anatomy 0.000 abstract description 28
- 230000010287 polarization Effects 0.000 abstract description 28
- 230000000694 effects Effects 0.000 abstract description 6
- 230000001737 promoting effect Effects 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 210000004322 M2 macrophage Anatomy 0.000 description 16
- 210000003690 classically activated macrophage Anatomy 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 12
- 108090000978 Interleukin-4 Proteins 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 239000002158 endotoxin Substances 0.000 description 8
- 229920006008 lipopolysaccharide Polymers 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 206010003246 arthritis Diseases 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 201000008482 osteoarthritis Diseases 0.000 description 6
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 3
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 3
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 230000006020 chronic inflammation Effects 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- 206010006448 Bronchiolitis Diseases 0.000 description 2
- 102000049320 CD36 Human genes 0.000 description 2
- 108010045374 CD36 Antigens Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000018565 Hemochromatosis Diseases 0.000 description 2
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 2
- 102100025136 Macrosialin Human genes 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- RKFAZBXYICVSKP-AATRIKPKSA-N alpha-asarone Chemical compound COC1=CC(OC)=C(\C=C\C)C=C1OC RKFAZBXYICVSKP-AATRIKPKSA-N 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 238000013043 cell viability test Methods 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 208000002574 reactive arthritis Diseases 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- UALKQROXOHJHFG-UHFFFAOYSA-N 1-ethoxy-3-methylbenzene Chemical compound CCOC1=CC=CC(C)=C1 UALKQROXOHJHFG-UHFFFAOYSA-N 0.000 description 1
- NBWRJAOOMGASJP-UHFFFAOYSA-N 2-(3,5-diphenyl-1h-tetrazol-1-ium-2-yl)-4,5-dimethyl-1,3-thiazole;bromide Chemical compound [Br-].S1C(C)=C(C)N=C1N1N(C=2C=CC=CC=2)N=C(C=2C=CC=CC=2)[NH2+]1 NBWRJAOOMGASJP-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010003256 Arthritis gonococcal Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010008690 Chondrocalcinosis pyrophosphate Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- -1 FLUIDEXTRACTS Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 201000010927 Mucositis Diseases 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 102000000536 PPAR gamma Human genes 0.000 description 1
- 108010016731 PPAR gamma Proteins 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 206010041591 Spinal osteoarthritis Diseases 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 208000002240 Tennis Elbow Diseases 0.000 description 1
- 206010044541 Traumatic shock Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 208000021240 acute bronchiolitis Diseases 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 210000004982 adipose tissue macrophage Anatomy 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 206010006475 bronchopulmonary dysplasia Diseases 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 208000002849 chondrocalcinosis Diseases 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 235000015927 pasta Nutrition 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 206010039722 scoliosis Diseases 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 208000005801 spondylosis Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Chemical class 0.000 description 1
- 229930003231 vitamin Chemical class 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/332—Promoters of weight control and weight loss
Abstract
Description
본 발명은 아사론산을 함유하는 조성물에 관한 것으로, 아사론산이 대식세포의 분극화에 영향을 미쳐 염증성 질환을 개선할 수 있는 식품 또는 치료 및 예방할 수 있는 약학 조성물에 관한 것이다.The present invention relates to a composition containing asaronic acid, and relates to a food or therapeutic and preventable pharmaceutical composition that can improve inflammatory diseases by affecting the polarization of macrophages.
염증(inflammation)이란 우리 몸 속에 유해한 자극원에 대한 생체반응 중 하나로 면역세포, 혈관, 분자생물학적인 중간체들이 관여되어 있는 보호반응이다. 염증 반응이 제대로 일어나지 않는다면, 세균과 같은 유해한 자극원들에 의해 점차적인 조직손상이 올 수 있으며 생명체의 생존을 위협할 수도 있다. 만성염증의 경우 치주염, 동맥경화증, 류마티스 관절염, 암과 같은 질병들을 유발할 수 있다.Inflammation is a protective response involving immune cells, blood vessels, and molecular biological intermediates as one of the biological responses to harmful stimuli in our body. If the inflammatory reaction does not occur properly, gradual tissue damage may be caused by harmful irritants such as bacteria and threaten the survival of life. Chronic inflammation can cause diseases such as periodontitis, arteriosclerosis, rheumatoid arthritis, and cancer.
대식세포는 주요한 염증세포로 알려져 있으며 분극화에 의해 두 가지 대식세포로 존재한다. M1 대식세포는 전염증(pro-inflammatory)의 특징을 가지고 염증성 대식세포의 형태를 띤다. LPS(Lipopolysaccharide)는 대식세포 매개 염증반응을 유발하는 대표적인 병원성 물질로 알려져 있으며, 대식세포 표면에 발현하는 TLR4와 결합하여 염증성 사이토카인(cytokines)의 분비를 통해 염증 반응을 유발한다.Macrophages are known as major inflammatory cells and exist as two macrophages by polarization. M1 macrophages are pro-inflammatory and take the form of inflammatory macrophages. Lipopolysaccharide (LPS) is known as a representative pathogenic agent that induces macrophage-mediated inflammatory reactions, and in combination with TLR4 expressed on the surface of macrophages, induces an inflammatory response through secretion of inflammatory cytokines.
이와 반대로, 항염증(anti-inflammatory)의 특징을 가지고 있는 M2 대식세포는 IL-4 및 IL-13과 같은 사이토카인에 의해 유도되며, IL-10과 같은 항염증성 사이토카인을 분비한다. 그에 따라 상처 회복 및 조직의 리모델링과 같은 항상성을 유지하는데 작용함으로써 염증을 해소하는데 주요한 역할을 한다.In contrast, M2 macrophages with anti-inflammatory properties are induced by cytokines such as IL-4 and IL-13, and secrete anti-inflammatory cytokines such as IL-10. It plays a major role in relieving inflammation by acting to maintain homeostasis, such as wound healing and tissue remodeling.
염증은 M1 및 M2 대식세포의 균형이 붕괴되는 상황에서 발생한다. M2 대식세포보다 M1 대식세포의 수가 많아지면 만성염증으로 이어진다. 따라서 M1 대식세포로의 분극을 억제하고 M2 대식세포로의 성장을 촉진하여 염증성 질환을 치료 및 예방하는 효과가 있는 물질에 대한 연구 개발의 필요성이 있다.Inflammation occurs when the balance of M1 and M2 macrophages is disrupted. More M1 macrophages than M2 macrophages lead to chronic inflammation. Therefore, there is a need for research and development of substances that are effective in treating and preventing inflammatory diseases by inhibiting polarization into M1 macrophages and promoting growth into M2 macrophages.
본 발명은 염증성 대식세포로의 분극을 억제하고 항염증성 대식세포로의 분극을 촉진하여 대식세포 발현 불균형을 억제하는 효과가 있는 아사론산(asaronic acid)을 함유하는 염증성 질환 개선용 식품 조성물 또는 염증성 질환 치료 및 예방용 약학 조성물을 제공하고자 한다.The present invention inhibits polarization into inflammatory macrophages and promotes polarization into anti-inflammatory macrophages, thereby improving the inflammatory disease-containing food composition or inflammatory disease containing asaronic acid, which is effective in suppressing macrophage expression imbalance. It is intended to provide a pharmaceutical composition for treatment and prevention.
본 발명은 아사론산(asaronic acid)을 유효성분으로 하는 염증 개선용 식품 조성물을 제공한다.The present invention provides a food composition for improving inflammation using asaronic acid as an active ingredient.
또한, 본 발명은 아사론산(asaronic acid)을 유효성분으로 하는 당뇨 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for improving diabetes using asaronic acid as an active ingredient.
또한, 본 발명은 아사론산(asaronic acid)을 유효성분으로 하는 비만 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for improving obesity using asaronic acid as an active ingredient.
본 발명 식품 조성물에 있어서, 상기 아사론산은, 바람직하게 1~20μM 함유되는 것이 좋다.In the food composition of the present invention, the asaronic acid is preferably contained 1 ~ 20μM.
한편, 본 발명은 아사론산(asaronic acid)을 유효성분으로 하는 염증 치료 및 예방용 약학 조성물을 제공한다.Meanwhile, the present invention provides a pharmaceutical composition for treating and preventing inflammation using asaronic acid as an active ingredient.
또한, 본 발명은 아사론산(asaronic acid)을 유효성분으로 하는 당뇨 치료 및 예방용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for the treatment and prevention of diabetes using asaronic acid (asaronic acid) as an active ingredient.
또한, 본 발명은 아사론산(asaronic acid)을 유효성분으로 하는 비만 치료 및 예방용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for the treatment and prevention of obesity using asaronic acid (asaronic acid) as an active ingredient.
본 발명 약학 조성물에 있어서, 상기 아사론산은, 바람직하게 1~20μM 함유되는 것이 좋다.In the pharmaceutical composition of the present invention, the asaronic acid is preferably contained 1 ~ 20μM.
본 발명은 아사론산을 함유하는 염증성 질환의 개선, 치료 및 예방용 조성물로서, 대식세포의 분극화를 억제 또는 촉진하여 대식세포의 발현 불균형을 억제하는 효과를 나타낸다. 따라서, 본 발명의 아사론산을 함유하는 조성물은 염증성 질환의 개선용 식품조성물 또는 치료 및 예방용 약학 조성물로 사용될 수 있다.The present invention, as a composition for the improvement, treatment and prevention of inflammatory diseases containing asaronic acid, exhibits the effect of suppressing or promoting the polarization of macrophages to suppress the expression imbalance of macrophages. Therefore, the composition containing asaronic acid of the present invention can be used as a food composition for improving inflammatory diseases or as a pharmaceutical composition for treatment and prevention.
도 1은 LPS를 J774A.1에 48시간 처리하였을 때 세포 생존을 나타내는 그래프이다.
도 2는 IL-4를 J774A.1에 48시간 처리하였을 때 세포 생존을 나타내는 그래프이다.
도 3은 아사론산(asaronic acid)의 농도를 달리하여 J774A.1에 48시간 처리하였을 때 세포 생존을 나타내는 그래프이다.
도 4는 아사론산(asaronic acid)의 M1 대식세포로의 분극 억제 효과를 확인한 웨스턴 블롯 결과이다.
도 5는 도 4에 따른 웨스턴 블롯 결과를 그래프로 도식화 한 것이다.
도 6은 아사론산(asaronic acid)이 대식세포 M2로의 분극을 촉진하는지 확인한 웨스턴 블롯 결과이다.
도 7은 도 6에 따른 웨스턴 블롯 결과를 그래프로 도식화 한 것이다.
도 8은 M2에서 발현되는 IL-10 발현량이 아사론산(asaronic acid)에 의해 증가하는 것을 확인한 ELISA 그래프이다.
도 9는 M2 대식세포에서 TGF- beta 발현양을 염색한 사진이다.1 is a graph showing cell survival when LPS was treated with J774A.1 for 48 hours.
2 is a graph showing cell survival when IL-4 was treated with J774A.1 for 48 hours.
3 is a graph showing cell survival when treated with J774A.1 for 48 hours at different concentrations of asaronic acid.
4 is a Western blot result confirming the effect of inhibiting polarization of asaronic acid to M1 macrophages.
FIG. 5 is a graph of the Western blot result according to FIG. 4.
6 is a Western blot result confirming that asaronic acid promotes polarization into macrophages M2.
7 is a graphical representation of the Western blot results according to FIG. 6.
8 is an ELISA graph confirming that the amount of IL-10 expressed in M2 is increased by asaronic acid.
Figure 9 is a photograph of staining the expression level of TGF- beta in M2 macrophages.
본 발명은 아사론산(asaronic acid)을 함유하는 염증 개선용 식품 조성물을 제공한다. 또한, 본 발명은 아사론산을 함유하는 염증 치료 및 예방용 약학 조성물을 제공한다.The present invention provides a food composition for improving inflammation containing asaronic acid. In addition, the present invention provides a pharmaceutical composition for the treatment and prevention of inflammation containing asaronic acid.
아사론산(asaronic acid)은 아사릴산(asarylic acid) 또는 2,4,5-트리메톡시벤조익산(2,4,5-trimethoxybenzoic acid)라고도 하며, 시중에서 구입하거나, 2,4,5-트리메톡시톨루엔을 산화하여 얻을 수 있다.Asaronic acid is also called asarylic acid or 2,4,5-trimethoxybenzoic acid, commercially available, or 2,4,5-tri It can be obtained by oxidizing methoxytoluene.
본 발명의 아사론산을 유효성분으로 포함하는 염증 개선용 식품 조성물 또는 염증 치료 및 예방용 약학 조성물에 있어서, 상기 아사론산은 M1 대식세포 분극화를 억제하고 M2 대식세포 분극화를 촉진하여 M1 및 M2 대식세포 발현 불균형을 조절하는 것을 특징으로 한다. M2 대식세포보다 M1 대식세포의 수가 많아지면 만성염증으로 이어지므로, M1 대식세포로의 분극화를 억제하고 M2 대식세포로의 성장을 촉진하여 M1 및 M2 대식세포 발현 불균형을 조절하면, 염증을 개선 또는 치료 또는 예방할 수 있다.In the food composition for improving inflammation or as a pharmaceutical composition for the treatment and prevention of inflammation comprising asaronic acid of the present invention as an active ingredient, the asaronic acid inhibits M1 macrophage polarization and promotes M2 macrophage polarization to promote M1 and M2 macrophages. It is characterized by controlling expression imbalance. When the number of M1 macrophages is greater than that of M2 macrophages, it leads to chronic inflammation, thereby suppressing polarization into M1 macrophages and promoting growth to M2 macrophages to control the imbalance of M1 and M2 macrophage expression, thereby improving inflammation or It can be treated or prevented.
또한, 본 발명은 아사론산(asaronic acid)을 유효성분으로 함유하는 당뇨 개선용 식품 조성물을 제공하고, 아사론산(asaronic acid)을 유효성분으로 함유하는 비만 개선용 식품 조성물을 제공한다. 또한, 본 발명은 아사론산(asaronic acid)을 유효성분으로 함유하는 당뇨 치료 및 예방용 약학 조성물을 제공하고, 아사론산(asaronic acid)을 유효성분으로 함유하는 비만 치료 및 예방용 약학 조성물을 제공한다. In addition, the present invention provides a food composition for improving diabetes, containing asaronic acid as an active ingredient, and a food composition for improving obesity, containing asaronic acid as an active ingredient. In addition, the present invention provides a pharmaceutical composition for treating and preventing diabetes containing asaronic acid as an active ingredient, and a pharmaceutical composition for treating and preventing obesity containing asaronic acid as an active ingredient. .
당뇨와 비만은 염증성 질환으로서 대식세포가 분극화되면 당뇨와 비만이 촉진될 수 있는 것으로 알려져 있는데, 하기 본 발명에 의할 경우, 아사론산에 의해 대식세포 분극이 억제되는 것으로 나타나, 당뇨와 비만이 억제될 수 있는 것으로 판단된다. Diabetes and obesity are inflammatory diseases, and it is known that diabetes and obesity can be promoted when macrophages are polarized. According to the present invention, it is shown that macrophages polarization is suppressed by asaronic acid, thereby suppressing diabetes and obesity. It seems to be possible.
한편, "대식세포 분극의 억제로 말미암아 당뇨와 비만이 억제될 수 있는 것"에 대한 참고문헌으로는, Julia Braune et al., IL-6 Regulates M2 Polarization and Local Proliferation of Adipose Tissue Macrophages in Obesity, The Journal of Immunology, February 13, 2017와 Linnan Zhu et al., Cellular Metabolism and Macrophage Functional Polarization, International Reviews of immunology, 34:82-100, 2015 등이 있다.On the other hand, as a reference to "which can be suppressed by diabetes and obesity due to the inhibition of macrophage polarization", Julia Braune et al., IL-6 Regulates M2 Polarization and Local Proliferation of Adipose Tissue Macrophages in Obesity, The Journal of Immunology, February 13, 2017 and Linnan Zhu et al., Cellular Metabolism and Macrophage Functional Polarization, International Reviews of immunology, 34: 82-100, 2015.
따라서, 아사론산이 대식세포 분극을 억제하는 것으로 확인한 본 발명은, '당뇨 또는 비만 개선용 식품 조성물' 또는 '당뇨 또는 비만의 치료 및 예방용 약학 조성물'로 사용될 수 있는 것이다. Therefore, the present invention confirmed that asaronic acid inhibits macrophage polarization can be used as a 'food composition for improving diabetes or obesity' or 'a pharmaceutical composition for treating and preventing diabetes or obesity'.
한편, 본 발명의 아사론산을 포함하는 조성물에 있어서, 상기 아사론산은 바람직하게 1 ~ 20 μM 함유되는 것이 좋다.On the other hand, in the composition comprising asaronic acid of the present invention, it is preferable that the asaronic acid is preferably contained in 1 ~ 20 μM.
한편, 염증으로 발생하는 질환은, 염증성 장 질환, 복막염, 골수염, 봉소염, 췌장염, 외상 유발 쇼크, 기관지 천식, 알러지성 비염, 낭포성 섬유증, 급성 기관지염, 만성 기관지염, 급성 세기관지염, 만성 세기관지염, 골관절염, 통풍, 척추관절병증, 강직성 척추염, 라이터 증후군, 건선성 관절병증, 장질환 척추염, 연소자성 관절병증, 연소자성 강직성 척추염, 반응성 관절병증, 감염성 관절염, 후-감염성 관절염, 임균성 관절염, 결핵성 관절염, 바이러스성 관절염, 진균성 관절염, 매독성 관절염, 라임 병, 혈관염 증후군과 관련된 관절염, 결절성 다발동맥염, 과민성 혈관염, 루게릭 육아종증, 류마티스성 다발성근육통, 관절 세포 동맥염, 칼슘 결정 침착 관절병증, 가성 통풍, 비-관절 류마티즘, 점액낭염, 건초염, 상과염(테니스 엘보), 신경병증성 관절 질환(neuropathic joint disease), 출혈성 관절증(hemarthrosic), 헤노흐-쉔라인 자반병, 비후성 골관절병증, 다중심성 세망조직구종, 척추측만증(scoliosis), 혈색소증, 혈색소병증, 고지단백혈증, 저감마글로불린혈증, 가족성 지중해열, 베하트 병, 전신성 홍반성 루푸스, 재귀열, 다발성 경화증, 패혈증, 패혈성 쇼크, 급성 호흡곤란 증후군, 다발성 장기부전, 만성 폐쇄성 폐질환(chronic obstructive pulmonary disease), 류마티스성 관절염(rheumatoid arthritis), 급성 폐손상(acute lung injury), 기관지 폐 형성장애(broncho-pulmonary dysplasia), 염증성 피부질환 등이 있는데, 항염 효과를 나타내는 본 발명은 이들 질환에 적용될 수 있다. On the other hand, diseases caused by inflammation include inflammatory bowel disease, peritonitis, osteomyelitis, rhinitis, pancreatitis, traumatic shock, bronchial asthma, allergic rhinitis, cystic fibrosis, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, Gout, spondylosis, ankylosing spondylitis, Reiter's syndrome, psoriatic arthrosis, bowel disease spondylitis, combustive arthrosis, combustive ankylosing spondylitis, reactive arthrosis, infectious arthritis, post-infectious arthritis, gonococcal arthritis, tuberculous arthritis, virus Sexual arthritis, fungal arthritis, syphilitic arthritis, Lyme disease, arthritis associated with vasculitis syndrome, nodular polyarthritis, irritable vasculitis, Lou Gehrig's granulomatosis, rheumatoid polymyalgia, articular cell arthritis, calcium crystal deposition arthrosis, pseudogout, non -Joint rheumatism, mucositis, hayitis, pericarditis (tennis elbow), neuropathic joint vagina (neuropathic joint disease), hemarthrosic, Henoch-Schlein purpura, hypertrophic osteoarthritis, multi-cardiac reticuloma, scoliosis, hemochromatosis, hemochromatosis, hyperlipoproteinemia, hypomagnoglobinemia, family Sexual Mediterranean fever, Behart's disease, systemic lupus erythematosus, recurrent fever, multiple sclerosis, sepsis, septic shock, acute respiratory distress syndrome, multiple organ failure, chronic obstructive pulmonary disease, rheumatoid arthritis ), Acute lung injury, broncho-pulmonary dysplasia, inflammatory skin disease, etc. The present invention showing anti-inflammatory effects can be applied to these diseases.
한편, 본 발명의 식품 조성물은 일 예로 육류, 곡류, 카페인 음료, 일반음료, 초콜렛, 빵류, 스넥류, 과자류, 피자, 젤리, 면류, 껌류, 아이스크림류, 알코올성 음료, 술, 비타민 복합제 및 그 밖의 건강보조식품류 중 선택되는 어느 하나일 수 있으며, 반드시 이에 한정되는 것은 아니다.On the other hand, the food composition of the present invention, for example, meat, cereals, caffeine beverages, general drinks, chocolate, bread, snacks, confectionery, pizza, jelly, noodles, gums, ice cream, alcoholic beverages, alcohol, vitamin complexes and other health It may be any one selected from supplements, and is not necessarily limited thereto.
한편, 본 발명의 약학 조성물은 약제학적으로 허용 가능한 담체, 희석제 또는 부형제를 더욱 포함할 수 있다. 사용가능한 담체, 부형제 또는 희석제로는 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물류가 있으며, 이중 선택되는 하나 이상을 사용할 수 있다. 또한, 치료 및 예방제가 약제인 경우 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제 또는 방부제 등이 추가적으로 포함될 수 있다.Meanwhile, the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, diluent or excipient. Usable carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, and crude Vaginal cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and minerals. One or more of these can be used. In addition, when the treatment and prevention agents are pharmaceuticals, fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers or preservatives may be additionally included.
한편, 본 발명의 약학 조성물의 제형은 사용 방법에 따라 바람직한 형태로 제조될 수 있으며, 특히 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 공지된 방법을 채택하여 제형화 하는 것이 좋다. 구체적인 제형의 예로는 경고제(PLASTERS), 과립제(GRANULES), 로션제(LOTIONS), 리니멘트제(LINIMENTS), 리모나데제(LEMONADES), 방향수제(AROMATIC WATERS), 산제(POWDERS), 시럽제(SYRUPS), 안연고제(OPHTALMIC OINTMENTS), 액제(LIQUIDS AND SOLUTIONS), 에어로솔제(AEROSOLS), 엑스제(EXTRACTS), 엘릭실제(ELIXIRS), 연고제(OINTMENTS), 유동엑스제(FLUIDEXTRACTS), 유제(EMULSIONS), 현탁제(SUSPESIONS), 전제(DECOCTIONS), 침제(INFUSIONS), 점안제(OPHTHALMIC SOLUTIONS), 정제(TABLETS), 좌제(SUPPOSITIORIES), 주사제(INJECTIONS), 주정제(SPIRITS), 카타플라스마제(CATAPLSMA), 캅셀제(CAPSULES), 크림제(CREAMS), 트로키제(TROCHES), 틴크제(TINCTURES), 파스타제(PASTES), 환제(PILLS), 연질 또는 경질 젤라틴 캅셀 중 선택되는 어느 하나일 수 있다.On the other hand, the formulation of the pharmaceutical composition of the present invention may be prepared in a preferred form according to the method of use, in particular, a method known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. It is good to adopt and formulate. Examples of specific formulations include warning agents (PLASTERS), granules (GRANULES), lotions (LOTIONS), linen agents (LINIMENTS), limonadeses (LEMONADES), fragrances (AROMATIC WATERS), powders (POWDERS), syrups ( SYRUPS), OPHTALMIC OINTMENTS, LIQUIDS AND SOLUTIONS, AEROSOLS, EXRACTS, ELIXIRS, OINTMENTS, FLUIDEXTRACTS, Emulsions (EMULSIONS) ), Suspension (SUSPESIONS), Premise (DECOCTIONS), Infusion (INFUSIONS), Eye drops (OPHTHALMIC SOLUTIONS), Tablets (TABLETS), Suppositories (SUPPOSITIORIES), Injections (INJECTIONS), Alcohol tablets (SPIRITS), Cataplastase (CATAPLSMA) ), Capsules (CAPSULES), creams (CREAMS), troches (TROCHES), tincture (TINCTURES), pasta (PASTES), pills (PILLS), may be any one selected from soft or hard gelatin capsules.
한편, 본 발명의 약학조성물에 있어서, 투여량은 투여방법, 복용자의 연령, 성별 및 체중 및 질환의 중증도 등을 고려하여 결정하는 것이 좋다. 일 예로, 유효성분인 아사론산을 기준(건조중량)으로 하였을 때 1일 0.1 내지 100mg/kg (체중)으로 1회 이상 투여 가능하다. 다만, 상기의 투여량은 예시하기 위한 일 예에 불과하며, 복용자의 상태와 의사의 처방에 의해 변화될 수 있다.On the other hand, in the pharmaceutical composition of the present invention, it is preferable to determine the dosage in consideration of the administration method, the age, sex and weight of the patient and the severity of the disease. For example, when the active ingredient asaronic acid is used as a reference (dry weight), it can be administered at least once at 0.1 to 100 mg / kg (body weight) per day. However, the above dosage is only an example for illustration, and may be changed by a patient's condition and a doctor's prescription.
한편, 본 발명에서 ‘유효성분으로 함유하는 것’의 의미는 본 발명에서 요구하는 M1 대식세포로의 분극화 억제 및 M2 대식세포로의 분극화 촉진의 효과가 본 발명의 성분인 아사론산으로부터 발생함을 의미하고, 그 외에 다른 성분을 보조성분으로 포함할 수 있음을 의미한다.Meanwhile, in the present invention, the meaning of 'containing as an active ingredient' means that the effect of inhibiting polarization to M1 macrophages and promoting polarization to M2 macrophages required by the present invention arises from asaronic acid, a component of the present invention. It means that other components can be included as auxiliary components.
이하, 본 발명의 내용에 대해 하기 실시예 및 실험예에서 더욱 상세히 설명하고자 한다. 다만, 본 발명의 권리범위가 하기 실시예에만 한정되는 것은 아니고, 이와 등가의 기술적 사상의 변형까지를 포함한다.Hereinafter, the contents of the present invention will be described in more detail in the following Examples and Experimental Examples. However, the scope of the present invention is not limited only to the following examples, and includes modifications of equivalent technical ideas.
[실시예 1 : 아사론산의 세포 생존률 시험][Example 1: Cell viability test of asaronic acid]
본 실시예에서 사용한 아사론산(asaronic acid)은 SIGMA(#138894)에서 구매한 2,4,5-트리메톡시벤조익산(2,4,5-Trimethoxybenzoic acid)이다.The asaronic acid used in this example is 2,4,5-trimethoxybenzoic acid purchased from SIGMA (# 138894).
(1) 마우스 대식세포(J774A.1) 배양(1) Mouse macrophage (J774A.1) culture
대식세포는 ‘mouse macrophage cell line’으로 J774A.1 세포주를 이용해 Dulbecco’s Modified Eagles’s Medium(DMEM) + 10% FBS 배지에 37℃, 5% CO2 조건에서 배양한 후 사용하였다. M1 대식세포로 분극화 시키기 위해 LPS (2㎍/ml)을 배지에 첨가한 뒤, 아사론산(asaronic acid)을 48시간 처리하였다. 또한, IL-4(40ng/ml)을 첨가한 배지에 아사론산(asaronic acid)을 48시간 처리하여 M2상태를 유도하였다.Macrophages were used after culturing in Dulbecco's Modified Eagles' Medium (DMEM) + 10% FBS medium at 37 ° C and 5% CO 2 using the J774A.1 cell line as a 'mouse macrophage cell line'. To polarize M1 macrophages, LPS (2 μg / ml) was added to the medium, followed by treatment with asaronic acid for 48 hours. Further, M2 state was induced by treating asaronic acid in the medium to which IL-4 (40ng / ml) was added for 48 hours.
(2) 세포 생존률 시험(Cell viability test)(2) Cell viability test
마우스 대식세포(J774A.1)를 LPS, IL-4, 아사론산(asaronic acid)과의 세포배양 실험을 거친 후 세포 생존율을 측정하기 위해서 자동 microplate reader spectrophtometer를 이용한 MTT 분석이 이루어졌다. 이 분석법은 tetrazlium MTT salt (3-(4,5-dimethylthiazol-2-yl)-2,5-di- phenyltetrazolium bromide)가 미토콘드리아 효소인 숙신산탈수소효소(succinate dehydrogenase)에 의해 불용성의 포르마잔(formazan)으로 변하는 과정을 이용하여 측정하였다.After the mouse macrophages (J774A.1) were subjected to cell culture experiments with LPS, IL-4, and asaronic acid, MTT analysis using an automatic microplate reader spectrophtometer was performed to measure cell viability. In this method, tetrazlium MTT salt (3- (4,5-dimethylthiazol-2-yl) -2,5-di-phenyltetrazolium bromide) is insoluble by the mitochondrial enzyme succinic dehydrogenase (formazan) It was measured using the process of changing to.
J774A.1 대식세포를 LPS(20ng/ml) 및 IL-4(40ng/ml)에 48시간 배양하고 세척한 후 MTT(5mg/ml stock solution)가 첨가된 phenol red가 들어있지 않은 배지에서 3시간 배양시켜서 확인하였다. 그 후에 isopropyl alcohol을 가하여 조심스럽게 흔들어 주면서 형성된 포르마잔(formazan)을 용해시키고 λ=570nm에서 흡광도를 측정하였다.After culturing and washing J774A.1 macrophages in LPS (20 ng / ml) and IL-4 (40 ng / ml) for 48 hours, after washing for 3 hours in a medium without phenol red added with MTT (5 mg / ml stock solution) It was confirmed by culturing. After that, isopropyl alcohol was added to gently dissolve the formed formazan, and absorbance was measured at λ = 570nm.
도 1은 LPS를 J774A.1에 48시간 처리하였을 때 세포 생존을 나타내는 그래프이고, 도 2는 IL-4를 J774A.1에 48시간 처리하였을 때 세포 생존을 나타내는 그래프이고, 도 3은 아사론산(asaronic acid)의 농도를 달리하여 J774A.1에 48시간 처리하였을 때 세포 생존을 나타내는 그래프이다.1 is a graph showing cell survival when LPS is treated with J774A.1 for 48 hours, FIG. 2 is a graph showing cell survival when IL-4 is treated with J774A.1 for 48 hours, and FIG. 3 shows asaronic acid ( asaronic acid) is a graph showing cell survival when treated with J774A.1 for 48 hours.
[실험예 1 : 대식세포 M1 분극화 억제 실험][Experimental Example 1: Macrophage M1 polarization inhibition experiment]
본 실험예에서는 M1에 특이적인 반응을 하는 대표적인 marker로 사용되는 TLR4, CD36, CD68의 단백질 발현 수준을 확인하였다.In this experimental example, the protein expression levels of TLR4, CD36, and CD68 used as representative markers that react specifically to M1 were confirmed.
M1 대식세포로 분극화 시키기 위해 2㎍/ml의 LPS와 아사론산(asaronic acid, SIGMA(#138894)의 2,4,5-Trimethoxybenzoic acid) 1, 10, 20μM을 각각 처리하고, 바이오마커의 단백질 수준을 확인하기 위해 웨스턴블럿(western blot) 분석법을 이용해 확인하였다. 세포 배양 후 라이시스버퍼(lysis buffer)를 이용해 셀 라이시스(cell lysis)를 실시하여 로우리(lowery) 단백질 정량법을 사용하여 동일한 양의 단백질을 SDS-PAGE에 전기영동하였다. 전기영동 후 SDS-PAGE에 분리된 단백질을 니트로섬유소막(nitrocellulose membrane)에 옮기고, 특이적 항원-항체 반응을 위해 블록킹(blocking), 일차항체(primary antibody), 이차항체(secondary antibody)를 반응시키고, ‘ECL solution’으로 발광시켜 엑스레이 필름(x-ray film)으로 검출하였다.To polarize M1 macrophages, 2 μg / ml LPS and 2,4,5-Trimethoxybenzoic acid (asaronic acid, SIGMA (# 138894) 2,4,5-Trimethoxybenzoic acid) were treated, respectively, and biomarker protein levels To confirm, it was confirmed by Western blot analysis. After cell culture, cell lysis was performed using a lysis buffer, and the same amount of protein was electrophoresed on SDS-PAGE using a lowery protein quantification method. After electrophoresis, the protein separated on the SDS-PAGE is transferred to a nitrocellulose membrane, and for blocking a specific antigen-antibody reaction, blocking, a primary antibody, and a secondary antibody are reacted. , Emitted with 'ECL solution' and detected with an x-ray film.
실험 결과, 아사론산(asaronic acid) 1, 10, 20μM을 첨가한 군에서 TLR4, CD36, CD68의 발현이 모두 감소(대조군으로 β-actin을 사용)하는 것으로 나타났다. 이로부터 아사론산(asaronic acid)가 M1 대식세포로의 분극화를 억제시키는 것을 확인 할 수 있었다. 도 4는 아사론산(asaronic acid)의 M1 대식세포로의 분극 억제 효과를 확인한 웨스턴 블롯(western blot) 결과이고, 도 5는 도 4에 따른 그래프이다.As a result of the experiment, it was found that the expression of TLR4, CD36, and CD68 in the group to which
[실험예 2 : 대식세포 M2 분극화 촉진 실험][Experimental Example 2: Macrophage M2 Polarization Promotion Experiment]
본 실험예에서는 본 발명의 아사론산(asaronic acid, SIGMA(#138894)의 2,4,5-Trimethoxybenzoic acid)이 대식세포 M2로의 분극을 촉진하는 효과가 있는지 확인하고자 하였다.In this experimental example, it was intended to confirm whether the asaronic acid of the present invention (2,4,5-Trimethoxybenzoic acid of SIGMA (# 138894)) has an effect of promoting polarization into macrophage M2.
IL-4에 의해 분극화되는 M2 대식세포에 아사론산(asaronic acid) 1, 10, 20μM을 각각 처리하여 M2 분극에 아사론산(asaronic acid)가 영향을 미치는지 확인하기 위하여 M2를 대표하는 마커인 Arginase-1, CD163, PPARγ를 관찰하였다. 바이오마커의 단백질 수준을 확인하기 위해 웨스턴블럿(western blot) 분석법을 이용하여 확인하였다. 세포 배양 후 라이시스 버퍼(lysis buffer)를 이용해 셀 라이시스(cell lysis)를 실시하여 로우리(lowery) 단백질 정량법을 사용해 동일한 양의 단백질을 SDS-PAGE에 전기영동하였다. 전기영동 후 SDS-PAGE에 분리된 단백질을 니트로섬유소막(nitrocellulose membrane)에 옮기고, 특이적 항원-항체 반응을 위해 블록킹(blocking), 일차항체(primary antibody), 이차항체(secondary antibody)를 반응시키고, ‘ECL solution’으로 발광시켜 엑스레이 필름(x-ray film)으로 검출하였다.Arginase-, a marker representing M2, to confirm whether asaronic acid affects M2 polarization by treating 1, 10, and 20 μM of asaronic acid to M2 macrophages polarized by IL-4 1, CD163 and PPARγ were observed. In order to confirm the protein level of the biomarker, it was confirmed using a Western blot analysis method. After cell culture, cell lysis was performed using a lysis buffer, and the same amount of protein was electrophoresed on SDS-PAGE using a lowery protein quantification method. After electrophoresis, the protein separated on the SDS-PAGE is transferred to a nitrocellulose membrane, and for blocking a specific antigen-antibody reaction, blocking, a primary antibody, and a secondary antibody are reacted. , Emitted with 'ECL solution' and detected with an x-ray film.
실험결과, 아사론산(asaronic acid) 1, 10, 20μM을 첨가한 군에서 M2 대식세포의 분극을 촉진하는 것을 확인하였다. 도 6은 아사론산(asaronic acid)이 대식세포 M2로의 분극을 촉진하는지 확인한 웨스턴블롯(western blot) 결과이고, 도 7은 도 6에 따른 그래프이다.As a result of the experiment, it was confirmed that the polarization of M2 macrophages was promoted in the group to which
또한, 세포에서 분비되는 사이토카인(cytokine)을 엘라이저(ELISA)로 확인하였다. 세포 배양 후 라이시스 하기 전 미디아(media)를 모아 원심분리기(centrifuge)로 3000rpm, 4℃, 10min을 돌린 후, 상층액 800㎕만을 가지고 ELISA 실험을 하였다. M2에서 가장 많이 분비되는 IL-10의 분비량을 확인한 결과 IL-4로 유도되는 M2 대식세포가 아사론산(asaronic acid)를 같이 처리하면 증가하는 것을 확인할 수 잇었다. 도 8은 M2에서 발현되는 IL-10 발현량이 아사론산(asaronic acid)에 의해 증가하는 것을 확인한 ELISA 그래프이다.In addition, cytokines secreted from cells were identified by ELISA. After cell culture and before lysis, media was collected and turned to 3000 rpm, 4 ° C., 10 min with a centrifuge, and ELISA experiments were performed with only 800 μl of the supernatant. As a result of confirming the secretion amount of IL-10, which is the most secreted from M2, it was confirmed that M2 macrophages induced by IL-4 increased when treated with asaronic acid. 8 is an ELISA graph confirming that the amount of IL-10 expressed in M2 is increased by asaronic acid.
[실험예 3 : TGF-beta 발현 실험][Experimental Example 3: TGF-beta expression experiment]
본 실험예에서는 cell 염색을 통해 M2 대식세포가 분극화 되면서 분비되는 TGF-beta 발현을 확인하였다.In this experimental example, TGF-beta expression secreted as M2 macrophages are polarized through cell staining was confirmed.
대식세포 J774A.1를 IL-4로 M2 분극화를 유도하면서 동시에 아사론산(asaronic acid, SIGMA(#138894)의 2,4,5-Trimethoxybenzoic acid) 1, 10, 20μM을 각각 처리한 후, 세포를 4% 포름알데히드(formaldehyde)로 고정하고, PBS로 충분히 씻어 준 후 5% BSA에 상온에서 1시간 블락킹(blocking)한 후 일차항체(primary antibody), 이차항체(secondary antibody)인 CY3(red) 반응시켰다. DAPI(blue)로 핵을 염색하고 세척하였다. 세척 후, 슬라이드 글라스 위에 봉입(mounting)하여 광학 현미경으로 관찰하였다. IL-4만으로 유도한 M2보다 아사론산(asaronic acid)을 같이 넣은 cell에서 TGF-beta 발현이 증가한 것을 확인할 수 있었다. 도 9는 M2 대식세포에서 TGF- beta 발현양을 염색한 사진이다.After macrophage J774A.1 induced M2 polarization with IL-4, treated with 2,4,5-Trimethoxybenzoic acid (1, 10, 20 μM of asaronic acid, SIGMA (# 138894)), and then treated with cells. It is fixed with 4% formaldehyde, washed sufficiently with PBS, blocked with 5% BSA for 1 hour at room temperature, and then primary antibody and secondary antibody CY3 (red) To react. Nuclei were stained and washed with DAPI (blue). After washing, it was mounted on a slide glass and observed with an optical microscope. It was confirmed that TGF-beta expression was increased in cells containing asaronic acid compared to M2 induced by IL-4 alone. 9 is a photograph of staining the expression level of TGF- beta in M2 macrophages.
Claims (8)
Food composition for improving inflammation containing asaronic acid as an active ingredient.
Food composition for improving diabetes, containing asaronic acid as an active ingredient.
Food composition for improving obesity containing asaronic acid as an active ingredient.
상기 아사론산은 1 ~ 20 μM 함유된 것을 특징으로 하는 식품 조성물.
According to any one of claims 1 to 3,
The asalonic acid is 1 to 20 μM food composition characterized in that it contains.
A pharmaceutical composition for treating and preventing inflammation containing asaronic acid as an active ingredient.
A pharmaceutical composition for the treatment and prevention of diabetes containing asaronic acid as an active ingredient.
A pharmaceutical composition for the treatment and prevention of obesity containing asaronic acid as an active ingredient.
상기 아사론산은 1 ~ 20 μM 함유된 것을 특징으로 하는 약학 조성물.
The method according to any one of claims 5 to 7,
The asaronic acid is a pharmaceutical composition characterized in that it contains 1 to 20 μM.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180105993A KR102126473B1 (en) | 2018-09-05 | 2018-09-05 | Composition for improvement, treatment or prevention of inflammatory diseases containing asaronic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180105993A KR102126473B1 (en) | 2018-09-05 | 2018-09-05 | Composition for improvement, treatment or prevention of inflammatory diseases containing asaronic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20200027769A true KR20200027769A (en) | 2020-03-13 |
| KR102126473B1 KR102126473B1 (en) | 2020-06-24 |
Family
ID=69938686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020180105993A KR102126473B1 (en) | 2018-09-05 | 2018-09-05 | Composition for improvement, treatment or prevention of inflammatory diseases containing asaronic acid |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR102126473B1 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20110040028A (en) * | 2009-10-13 | 2011-04-20 | 숙명여자대학교산학협력단 | Pharmaceutical composition and functional health food for preventing or treating diabetes mellitus comprising asarone as effective component |
| KR20120138333A (en) * | 2011-06-15 | 2012-12-26 | 건국대학교 산학협력단 | Pharmaceutical composition and functional food for preventing or treating neurodegenerative disease by acorus gramineus extracts and alpha-asarone as effective component |
| KR101672708B1 (en) | 2015-09-14 | 2016-11-04 | 한림대학교 산학협력단 | - Food composition for improvement of atherosclerosis and pharmaceutical compositions for treatment of atherosclerosis with extract of Perilla frutescens or -asarone from Perilla frutescens |
| KR101733048B1 (en) | 2014-05-30 | 2017-05-08 | 한림대학교 산학협력단 | Improving Vascular Disorder Related Cholesterol Metabolism Food Composition Containing Solidago Virgaurea Extract and Method for Preparing the Same |
-
2018
- 2018-09-05 KR KR1020180105993A patent/KR102126473B1/en active IP Right Grant
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20110040028A (en) * | 2009-10-13 | 2011-04-20 | 숙명여자대학교산학협력단 | Pharmaceutical composition and functional health food for preventing or treating diabetes mellitus comprising asarone as effective component |
| KR20120138333A (en) * | 2011-06-15 | 2012-12-26 | 건국대학교 산학협력단 | Pharmaceutical composition and functional food for preventing or treating neurodegenerative disease by acorus gramineus extracts and alpha-asarone as effective component |
| KR101733048B1 (en) | 2014-05-30 | 2017-05-08 | 한림대학교 산학협력단 | Improving Vascular Disorder Related Cholesterol Metabolism Food Composition Containing Solidago Virgaurea Extract and Method for Preparing the Same |
| KR101672708B1 (en) | 2015-09-14 | 2016-11-04 | 한림대학교 산학협력단 | - Food composition for improvement of atherosclerosis and pharmaceutical compositions for treatment of atherosclerosis with extract of Perilla frutescens or -asarone from Perilla frutescens |
Non-Patent Citations (4)
| Title |
|---|
| David J. Kouba 외 5명, "Tumor Necrosis Factor-α Induces Distinctive NF-κB Signaling within Human Dermal Fibroblasts", The Journal of Biological Chemistry, Vol. 276, No. 9, pp 6214-6224(온라인 공개일: 2000.11. * |
| Jenny E. Kanter, et al. "Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis thorough acyl-CoA synthetase 1", PNAS, January 17, 2012, E715-E724 |
| M J Tomy 외 5명, "In vitro Assessment of Selected Benzoic Acid Derivatives as Anti-Inflammatory Compounds", Journal of Scientific & Industrial Research, Vol. 77, No. 6, pp 330-336, 2018.06. * |
| Rafikali A. Momin 외 2명, "Inhibition of cyclooxygenase (COX) enzymes by compounds from Daucus carota L. Seeds", Phytother Res, Vol. 17, No. 8, pp 976-979, 2003.09. * |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102126473B1 (en) | 2020-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Bernardi et al. | Polyphenols and intestinal permeability: rationale and future perspectives | |
| Medina et al. | Metabolic syndrome, autoimmunity and rheumatic diseases | |
| Xiao et al. | Rice bran phenolic extract protects against alcoholic liver injury in mice by alleviating intestinal microbiota dysbiosis, barrier dysfunction, and liver inflammation mediated by the endotoxin–TLR4–NF-κB pathway | |
| Diwan et al. | The flavonoid rutin improves kidney and heart structure and function in an adenine-induced rat model of chronic kidney disease | |
| Arroba et al. | Modulation of microglia polarization dynamics during diabetic retinopathy in db/db mice | |
| de Mejia et al. | Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-κB pathway in the macrophage | |
| Murugaiyah et al. | Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents | |
| Jiao et al. | Role of IFN‐γ, IL‐13, and IL‐17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps | |
| Lin et al. | The protective effect of hesperetin in osteoarthritis: an in vitro and in vivo study | |
| Lee et al. | Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80 | |
| Qiu et al. | Ginsenoside Rh2 promotes nonamyloidgenic cleavage of amyloid precursor protein via a cholesterol-dependent pathway | |
| An et al. | Isoorientin exerts a urate-lowering effect through inhibition of xanthine oxidase and regulation of the TLR4-NLRP3 inflammasome signaling pathway | |
| Zhou et al. | Targeting microglial autophagic degradation of the NLRP3 inflammasome for identification of thonningianin A in Alzheimer’s disease | |
| Hou et al. | Lycium barbarum polysaccharide exhibits cardioprotection in an experimental model of ischemia-reperfusion damage | |
| Chen et al. | Bioactivity-guided isolation of the major anthocyanin from Lycium ruthenicum Murr. fruit and its antioxidant activity and neuroprotective effects in vitro and in vivo | |
| Cai et al. | Quercetin protects RAW264. 7 macrophages from glucosamine-induced apoptosis and lipid accumulation via the endoplasmic reticulum stress pathway | |
| Menshawey et al. | Shedding light on vitamin D: the shared mechanistic and pathophysiological role between hypovitaminosis D and COVID-19 risk factors and complications | |
| Li et al. | Purpurogallin improves neurological functions of cerebral ischemia and reperfusion mice by inhibiting endoplasmic reticulum stress and neuroinflammation | |
| Ahn et al. | Fructose-arginine, a non-saponin molecule of Korean Red Ginseng, attenuates AIM2 inflammasome activation | |
| EP1882472B1 (en) | Drugs, food or drink for improving pancreatic functions | |
| Wang et al. | Protective effects of total flavonoids from Qu Zhi Qiao (fruit of Citrus paradisi cv. Changshanhuyou) on OVA-induced allergic airway inflammation and remodeling through MAPKs and Smad2/3 signaling pathway | |
| EP2799082B1 (en) | Pharmaceutical composition for preventing or treating inflammatory diseases or asthma, containing lagerstroemia ovalifolia extract or fraction thereof as active ingredient | |
| Rajasekar et al. | Anti-asthmatic effects of tannic acid from Chinese natural gall nuts in a mouse model of allergic asthma | |
| EP1808175B1 (en) | Drug and food or drink for improving pancreatic functions | |
| KR102126473B1 (en) | Composition for improvement, treatment or prevention of inflammatory diseases containing asaronic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| AMND | Amendment | ||
| X701 | Decision to grant (after re-examination) | ||
| GRNT | Written decision to grant |