CN115554281A - 番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用 - Google Patents
番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用 Download PDFInfo
- Publication number
- CN115554281A CN115554281A CN202211294188.6A CN202211294188A CN115554281A CN 115554281 A CN115554281 A CN 115554281A CN 202211294188 A CN202211294188 A CN 202211294188A CN 115554281 A CN115554281 A CN 115554281A
- Authority
- CN
- China
- Prior art keywords
- lycopene
- symptoms
- product
- alcoholic steatohepatitis
- liver
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 title claims abstract description 114
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 title claims abstract description 89
- 235000012661 lycopene Nutrition 0.000 title claims abstract description 89
- 239000001751 lycopene Substances 0.000 title claims abstract description 89
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 title claims abstract description 87
- 229960004999 lycopene Drugs 0.000 title claims abstract description 87
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 title claims abstract description 87
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 title claims abstract description 44
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 title claims abstract description 43
- 208000024891 symptom Diseases 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims description 11
- 230000036542 oxidative stress Effects 0.000 claims abstract description 13
- 210000003494 hepatocyte Anatomy 0.000 claims abstract description 11
- 230000004065 mitochondrial dysfunction Effects 0.000 claims abstract description 10
- 230000002438 mitochondrial effect Effects 0.000 claims abstract description 10
- 230000037356 lipid metabolism Effects 0.000 claims abstract description 9
- 230000001640 apoptogenic effect Effects 0.000 claims abstract description 6
- 230000008961 swelling Effects 0.000 claims abstract description 5
- 210000004185 liver Anatomy 0.000 claims description 45
- 235000021588 free fatty acids Nutrition 0.000 claims description 21
- 239000000047 product Substances 0.000 claims description 20
- 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 claims description 18
- 150000002632 lipids Chemical class 0.000 claims description 15
- 235000012000 cholesterol Nutrition 0.000 claims description 9
- 230000003247 decreasing effect Effects 0.000 claims description 9
- 235000013305 food Nutrition 0.000 claims description 9
- 102000016938 Catalase Human genes 0.000 claims description 8
- 108010053835 Catalase Proteins 0.000 claims description 8
- 102000019197 Superoxide Dismutase Human genes 0.000 claims description 8
- 108010012715 Superoxide dismutase Proteins 0.000 claims description 8
- 150000005830 nonesterified fatty acids Chemical class 0.000 claims description 8
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 claims description 7
- 229940118019 malondialdehyde Drugs 0.000 claims description 7
- OAIJSZIZWZSQBC-OUUYXACASA-N cis-lycopene Natural products CC(=CCCC(=CC=CC(=C/C=C/C(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C=C(C)/CCC=C(C)C)/C)C)C)C OAIJSZIZWZSQBC-OUUYXACASA-N 0.000 claims description 6
- 230000008021 deposition Effects 0.000 claims description 6
- 206010016654 Fibrosis Diseases 0.000 claims description 5
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- OAIJSZIZWZSQBC-GKJNUFSQSA-N Prolycopene Natural products CC(=CCCC(=C/C=C/C(=C/C=C/C(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C=C(C)/CCC=C(C)C)/C)/C)C)C OAIJSZIZWZSQBC-GKJNUFSQSA-N 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 102000006587 Glutathione peroxidase Human genes 0.000 claims description 3
- 108700016172 Glutathione peroxidases Proteins 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 230000007882 cirrhosis Effects 0.000 claims description 3
- 235000015872 dietary supplement Nutrition 0.000 claims description 3
- 230000037406 food intake Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 3
- OAIJSZIZWZSQBC-AGNXDNEMSA-N (6E,8E,10E,12Z,14E,16E,18E,20E,22E,24E,26E)-2,6,10,14,19,23,27,31-octamethyldotriaconta-2,6,8,10,12,14,16,18,20,22,24,26,30-tridecaene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C/C=C(\C)/C=C/C=C(\C)CCC=C(C)C OAIJSZIZWZSQBC-AGNXDNEMSA-N 0.000 claims description 2
- OAIJSZIZWZSQBC-YBXDGGNMSA-N (6E,8Z,10E,12E,14E,16E,18E,20E,22E,24E,26E)-2,6,10,14,19,23,27,31-octamethyldotriaconta-2,6,8,10,12,14,16,18,20,22,24,26,30-tridecaene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C/C=C(\C)CCC=C(C)C OAIJSZIZWZSQBC-YBXDGGNMSA-N 0.000 claims description 2
- OAIJSZIZWZSQBC-FZXCKFLSSA-N 13-cis-lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C/C=C/C=C(\C)/C=C/C=C(\C)/C=C/C=C(\C)CCC=C(C)C OAIJSZIZWZSQBC-FZXCKFLSSA-N 0.000 claims description 2
- OAIJSZIZWZSQBC-KFVHJVEESA-N 13-cis-lycopene Natural products CC(=CCCC(=CC=CC(=CC=CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C=C(C)/CCC=C(C)C)C)C)C)C OAIJSZIZWZSQBC-KFVHJVEESA-N 0.000 claims description 2
- OAIJSZIZWZSQBC-XKKDEUFYSA-N 15-cis-lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C/C=C(\C)/C=C/C=C(\C)/C=C/C=C(\C)CCC=C(C)C OAIJSZIZWZSQBC-XKKDEUFYSA-N 0.000 claims description 2
- OAIJSZIZWZSQBC-VIKDNVIHSA-N 15-cis-lycopene Natural products CC(=CCCC(=CC=CC(=CC=CC(=CC=C/C=C(C)/C=C/C=C(C)/C=C/C=C(C)/CCC=C(C)C)C)C)C)C OAIJSZIZWZSQBC-VIKDNVIHSA-N 0.000 claims description 2
- OAIJSZIZWZSQBC-IKZLVQEUSA-N 5-cis-lycopene Chemical compound CC(C)=CCC\C(C)=C/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(\C)/C=C/C=C(\C)/C=C/C=C(\C)CCC=C(C)C OAIJSZIZWZSQBC-IKZLVQEUSA-N 0.000 claims description 2
- OAIJSZIZWZSQBC-CBEQXLMWSA-N 9-cis-lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C/C=C/C(/C)=C/C=C/C=C(\C)/C=C/C=C(\C)/C=C/C=C(\C)CCC=C(C)C OAIJSZIZWZSQBC-CBEQXLMWSA-N 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 239000003463 adsorbent Substances 0.000 claims description 2
- 235000013361 beverage Nutrition 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003623 enhancer Substances 0.000 claims description 2
- 239000003889 eye drop Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000010408 film Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract description 28
- 210000005229 liver cell Anatomy 0.000 abstract description 13
- 235000005911 diet Nutrition 0.000 abstract description 11
- 230000037213 diet Effects 0.000 abstract description 11
- 208000017170 Lipid metabolism disease Diseases 0.000 abstract description 7
- 208000006454 hepatitis Diseases 0.000 abstract description 7
- 231100000283 hepatitis Toxicity 0.000 abstract description 6
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 abstract description 5
- 229930182817 methionine Natural products 0.000 abstract description 5
- 230000001476 alcoholic effect Effects 0.000 abstract description 3
- 208000019423 liver disease Diseases 0.000 abstract description 3
- 230000002503 metabolic effect Effects 0.000 abstract description 3
- 208000004481 Choline Deficiency Diseases 0.000 abstract description 2
- 208000021752 choline deficiency disease Diseases 0.000 abstract description 2
- 235000021196 dietary intervention Nutrition 0.000 abstract description 2
- 230000001737 promoting effect Effects 0.000 abstract description 2
- 230000001681 protective effect Effects 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 50
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 238000010186 staining Methods 0.000 description 15
- 150000003626 triacylglycerols Chemical class 0.000 description 14
- 230000006907 apoptotic process Effects 0.000 description 11
- 239000003642 reactive oxygen metabolite Substances 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 210000003470 mitochondria Anatomy 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 230000004898 mitochondrial function Effects 0.000 description 7
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 206010019668 Hepatic fibrosis Diseases 0.000 description 6
- 102000017946 PGC-1 Human genes 0.000 description 6
- 108700038399 PGC-1 Proteins 0.000 description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 6
- 230000006372 lipid accumulation Effects 0.000 description 6
- 210000005228 liver tissue Anatomy 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 5
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 5
- 239000005642 Oleic acid Substances 0.000 description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 5
- 239000013589 supplement Substances 0.000 description 5
- 241001133760 Acoelorraphe Species 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 206010067125 Liver injury Diseases 0.000 description 4
- 102000023984 PPAR alpha Human genes 0.000 description 4
- 102100028960 Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002285 corn oil Substances 0.000 description 4
- 235000005687 corn oil Nutrition 0.000 description 4
- 230000037149 energy metabolism Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 210000001700 mitochondrial membrane Anatomy 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000010998 test method Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108010028924 PPAR alpha Proteins 0.000 description 3
- 235000021314 Palmitic acid Nutrition 0.000 description 3
- 230000003044 adaptive effect Effects 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229960001231 choline Drugs 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 231100000753 hepatic injury Toxicity 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000003908 liver function Effects 0.000 description 3
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 3
- 238000012764 semi-quantitative analysis Methods 0.000 description 3
- 238000002791 soaking Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 108091033409 CRISPR Proteins 0.000 description 2
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 2
- 102100029764 DNA-directed DNA/RNA polymerase mu Human genes 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 101001123331 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Proteins 0.000 description 2
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 108090000310 Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Proteins 0.000 description 2
- 240000003768 Solanum lycopersicum Species 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- MDKCFLQDBWCQCV-UHFFFAOYSA-N benzyl isothiocyanate Chemical compound S=C=NCC1=CC=CC=C1 MDKCFLQDBWCQCV-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- UBAXRAHSPKWNCX-UHFFFAOYSA-N diallyl trisulfide Chemical compound C=CCSSSCC=C UBAXRAHSPKWNCX-UHFFFAOYSA-N 0.000 description 2
- 230000009266 disease activity Effects 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000008810 intracellular oxidative stress Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000013424 sirius red staining Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000007863 steatosis Effects 0.000 description 2
- 231100000240 steatosis hepatitis Toxicity 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013042 tunel staining Methods 0.000 description 2
- 210000003934 vacuole Anatomy 0.000 description 2
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 1
- RTRQQBHATOEIAF-UHFFFAOYSA-N AICA riboside Natural products NC1=C(C(=O)N)N=CN1C1C(O)C(O)C(CO)O1 RTRQQBHATOEIAF-UHFFFAOYSA-N 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 108050006685 Apoptosis regulator BAX Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 244000241235 Citrullus lanatus Species 0.000 description 1
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 208000035762 Disorder of lipid metabolism Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- QAADZYUXQLUXFX-UHFFFAOYSA-N N-phenylmethylthioformamide Natural products S=CNCC1=CC=CC=C1 QAADZYUXQLUXFX-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- 235000011034 Rubus glaucus Nutrition 0.000 description 1
- 244000235659 Rubus idaeus Species 0.000 description 1
- 235000009122 Rubus idaeus Nutrition 0.000 description 1
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000013200 Stress disease Diseases 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 235000021068 Western diet Nutrition 0.000 description 1
- RTRQQBHATOEIAF-UUOKFMHZSA-N acadesine Chemical compound NC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RTRQQBHATOEIAF-UUOKFMHZSA-N 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- FXAGBTBXSJBNMD-UHFFFAOYSA-N acetic acid;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O FXAGBTBXSJBNMD-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960001570 ademetionine Drugs 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 235000016720 allyl isothiocyanate Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 101150038500 cas9 gene Proteins 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 230000003081 coactivator Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229940045109 genistein Drugs 0.000 description 1
- 235000006539 genistein Nutrition 0.000 description 1
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 229940087603 grape seed extract Drugs 0.000 description 1
- 235000002532 grape seed extract Nutrition 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- IZJDOKYDEWTZSO-UHFFFAOYSA-N phenethyl isothiocyanate Chemical compound S=C=NCCC1=CC=CC=C1 IZJDOKYDEWTZSO-UHFFFAOYSA-N 0.000 description 1
- 229940117953 phenylisothiocyanate Drugs 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- PUIBPGHAXSCVRF-QHFGJBOXSA-N prostaglandin C1 Chemical compound CCCCC[C@H](O)\C=C\C1=CCC(=O)[C@@H]1CCCCCCC(O)=O PUIBPGHAXSCVRF-QHFGJBOXSA-N 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 108091035539 telomere Proteins 0.000 description 1
- 102000055501 telomere Human genes 0.000 description 1
- 210000003411 telomere Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 239000001717 vitis vinifera seed extract Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Images
Classifications
-
- 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
- A61K31/01—Hydrocarbons
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/38—Other non-alcoholic beverages
-
- 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
-
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Food Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Botany (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本发明公开了一种番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，所述非酒精性脂肪肝炎症状由肝细胞线粒体功能障碍引起，其特征在于，所述肝细胞线粒体功能障碍包括：肝细胞凋亡数量增加、氧化应激水平升高、脂质代谢紊乱或线粒体形态肿胀。本申请所述的番茄红素对蛋氨酸胆碱缺乏膳食(MCD)和高脂高胆固醇饮食(HFHC)诱导的小鼠非酒精性脂肪肝炎模型显示出明显的保护作用，还可以改善HepG2细胞脂质代谢紊乱。本发明提供的番茄红素用于改善非酒精性脂肪肝炎症状的应用能够为改善、治疗代谢性相关肝病包括NASH开辟新的膳食干预途径，这对于拓展番茄红素在市场上的应用具有显著的推进作用。
Description
技术领域
本发明属于食品营养技术领域，特别涉及番茄红素在制备改善非酒精性脂肪肝炎(nonalcoholic steatohepatitis,NASH)症状的产品中的应用。
背景技术
非酒精性脂肪肝炎作为代谢相关脂肪性肝病，是指一种无过量饮酒史，以肝实质细胞脂肪蓄积变性，肝脏损伤和炎症，以及不同程度的纤维化为特征的临床病理综合征。NASH可以导致肝脏功能严重损伤、硬化甚至肝衰竭而死亡。
非酒精性脂肪肝炎发病进程极其复杂。饮食习惯，环境因素和肥胖会导致血清中的游离脂肪酸(free fattyacids,FFA)和胆固醇水平升高，出现胰岛素抵抗，脂肪细胞增殖和功能障碍。过量积累的甘油三酯(triglycerides,TG)、"有毒"水平的FFA、游离胆固醇和其他脂质代谢物，会导致线粒体功能障碍，产生氧化应激和活性氧自由基(reactiveoxygen species,ROS)都会影响肝细胞脂肪含量和肝脏炎症环境，最终导致肝细胞死亡和纤维基质的沉积。
线粒体，是ATP生产的主要位置和ROS的主要来源，在许多细胞活动中起着重要的调节作用。过度的细胞内脂质沉积促进氧化应激反应，产生过量的ROS，从而导致线粒体功能障碍和细胞毒性。这促进了恶性循环，加剧了NASH的发展。过氧化物酶体增殖物激活受体γ辅激活子1α(PGC-1α)是一种重要的转录共激活因子，是线粒体生物合成和能量代谢的中心诱导剂。
番茄红素是一种强大的抗氧化剂，能够对抗蛋白质、脂质和DNA的氧化，且广泛存在于番茄、番茄制品及西瓜、葡萄柚等水果中。近年来研究表明，膳食补充番茄红素能够起到抑制肥胖、治疗心血管疾病和预防癌症等多种作用。专利CN102612564A公开了一种抗氧化剂，用于改善线粒体功能的使用，在不分裂细胞和分裂静止细胞中维持不分裂状态，预防或治疗与的线粒体功能加速丧失、染色体端粒功能异常和不分裂细胞死亡有关的老年性疾病。试剂选自AICAR、低剂量雷帕霉素或它的类似物、EGCG、葡萄籽提取物、覆盆子提取物、亚硒酸钠、染料木素、二烯丙基三硫、苯基异硫氰酸酯、苄基异硫氰酸酯、异硫氰酸苯乙酯、白藜芦醇、番茄红素以及异硫氰酸烯丙酯。但对于单独的番茄红素本身是否具有改善线粒体功能的效果，进而对非酒精性脂肪肝炎造成的症状是否有改善作用，目前尚未见文献报道。
发明内容
针对上述技术问题，本发明目的在于提出一种番茄红素的新用途，即番茄红素用于改善非酒精性脂肪肝炎的应用，具体技术方案如下：
番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，所述非酒精性脂肪肝炎症状由肝细胞线粒体功能障碍引起，所述肝细胞线粒体功能障碍包括：肝细胞凋亡数量增加、氧化应激水平升高、脂质代谢紊乱或线粒体形态肿胀。
进一步地，所述产品包括药物、膳食补充剂、食品或饮料。
进一步地，所述非酒精性脂肪肝炎症状包括：肝纤维化、肝脏肿大硬化、肝内脂质沉积或血脂升高。
进一步地，所述脂质代谢紊乱包括胆固醇含量升高、甘油三酯含量升高和非酯化脂肪酸含量升高；所述氧化应激水平升高包括超氧化物歧化酶水平降低、过氧化氢酶水平降低、谷胱甘肽过氧化物酶水平降低或丙二醛水平升高。
进一步地，所述番茄红素的分子式为C40H56，所述番茄红素的分子结构包括反式番茄红素或顺式番茄红素中的一种或几种。
进一步地，所述反式番茄红素为全反式番茄红素；所述顺式番茄红素包括15顺式番茄红素、13顺式番茄红素、11顺式番茄红素、9顺式番茄红素、7顺式番茄红素或5顺式番茄红素中的一种或几种。
本发明所述反式和顺式番茄红素异构体的结构式如下式(I)所示：
进一步地，所述产品中还包含药学上或食品上可接受的载体或辅料。
优选地，所述药学上或食品上可接受的辅料包括稀释剂、赋形剂、填充剂、粘合剂、润湿剂、崩解剂、吸收促进剂、表面活性剂、吸附剂或润滑剂。
优选地，所述药学上或食品上可接受的载体包括片剂、散剂、丸剂、注射剂、胶囊剂、膜剂、栓剂、膏剂或冲剂。
优选地，所述产品通过注射、喷射、滴鼻、滴眼、渗透或摄入的方法导入机体。
应理解，在本发明范围内中，本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合，从而构成新的或优选的技术方案。说明书中所揭示的各个特征，可以被任何提供相同、均等或相似目的的替代性特征取代。限于篇幅，在此不再一一赘述。
与现有技术相比，本发明的有益效果在于：
(1)本发明提供的番茄红素用于改善非酒精性脂肪肝炎症状的应用表明，番茄红素对蛋氨酸胆碱缺乏膳食(MCD)和高脂高胆固醇饮食(HFHC)诱导肝炎模型有良好的功效，无不良反应，可以有效地改善肝炎小鼠血脂异常，降低转氨酶水平；减轻肝脏脂质变性和炎症；降低肝纤维化和肝脏细胞凋亡水平。
(2)本发明提供的番茄红素用于改善非酒精性脂肪肝炎症状的应用表明，通过激活过氧化物酶体增殖物激活受体γ辅激活子1α(PGC-1α)恢复肝细胞的线粒体功能，能够为改善、治疗代谢性相关肝病包括NASH，开辟新的膳食干预途径，这对于拓展番茄红素在市场上的应用具有显著的推进作用。
附图说明
下面对说明书附图所表达的内容做简要说明：
图1为实施例1中CON空白对照组、MCD模型组和LYC番茄红素干预组的小鼠肝脏指数变化检测结果；
图2为实施例1中CON空白对照组、MCD模型组和LYC番茄红素干预组的小鼠肝脏组织病理切片图；
图3为实施例1中CON空白对照组、MCD模型组和LYC番茄红素干预组的小鼠肝脏脂质代谢水平检测结果；
图4为实施例1中CON空白对照组、MCD模型组和LYC番茄红素干预组的小鼠肝脏氧化应激相关酶系水平检测结果；
图5为实施例1中CON空白对照组、MCD模型组和LYC番茄红素干预组的小鼠肝细胞原位末端转移酶标记(TUNEL)染色结果；
图6为实施例1中CON空白对照组、MCD模型组和LYC番茄红素干预组的小鼠肝细胞凋亡指数检测结果；
图7为实施例2中CW+C空白对照组、HFHC+C模型组、HFHC+LP3低剂量番茄红素干预组和HFHC+LP6高剂量番茄红素干预组的小鼠肝脏细胞线粒体透射电镜图；
图8为实施例3中CW+C空白对照组、HFHC+C模型组、HFHC+LP3低剂量番茄红素干预组和HFHC+LP6高剂量番茄红素干预组的小鼠细胞脂质沉积水平检测结果；
图9为实施例3中CW+C空白对照组、HFHC+C模型组、HFHC+LP3低剂量番茄红素干预组和HFHC+LP6高剂量番茄红素干预组的小鼠细胞油红O染色结果；
图10为实施例3中CON空白细胞组、FFA油酸棕榈树造模组和LYC番茄红素干预组小鼠的细胞ROS荧光染色图；
图11为实施例3中CON空白细胞组、FFA油酸棕榈树造模组和LYC番茄红素干预组小鼠的细胞ROS半定量分析结果；
图12为实施例3中CON空白细胞组、FFA油酸棕榈树造模组和LYC番茄红素干预组小鼠的细胞线粒体膜电势JC-1染色图；
图13为实施例3中CON空白细胞组、FFA油酸棕榈树造模组和LYC番茄红素干预组小鼠的HepG2细胞凋亡及线粒体能量代谢调节相关基因表达检测结果。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其它实施例，都属于本发明保护的范围。
实施例1
采用蛋氨酸胆碱缺乏膳食(MCD)诱导小鼠的非酒精脂肪肝炎模型：MCD饮食的配方要求用结晶氨基酸取代纯化饮食中的全蛋白，并去除蛋氨酸和胆碱。MCD模型中，脂肪变性到NASH的进展涉及下调线粒体中S-腺苷蛋氨酸，导致谷胱甘肽下降，线粒体功能障碍，这进一步导致氧化应激和炎症造成的肝细胞损伤的增加。此外，MCD饮食相对于其他造模方法更接近于模拟人类NASH的发病机制。
1.1试验方法
(1)动物分组：将6周龄C57BL/6J雄性小鼠(体重18～22g)饲养于标准SPF屏障环境，保持恒温(22℃)、恒湿(55％)、12小时昼夜交替以及自由摄食和饮水。适应性饲养1周后，将18只小鼠平均分为空白对照(CON)组、MCD模型组和LYC番茄红素干预组，3组小鼠自由饮水。
(2)给药方法：适应性饲养1周后，LYC组小鼠每日给予番茄红素溶液0.25mL(剂量：6mg/kg/day)，番茄红素临使用前用食用玉米油进行溶解；CON组与MCD组给予0.25mL食用玉米油，每天灌胃一次，连续给药6周。
(3)模型建立：采用MCD饲料诱导小鼠非酒精性脂肪肝炎模型，MCD模型组和LYC番茄红素干预组饲喂MCD饲料，空白对照(CON)组饲喂不缺乏蛋氨酸和胆碱的MCS饲料。在试验过程中，每日记录小鼠体重、摄食状态。
(4)组织处理：实验结束后，解剖小鼠。收集新鲜小鼠肝脏，部分浸泡于10％福尔马林中，进行H&E染色、天狼星红染色和TUNEL染色，并进行NAS评分；部分直接制备冷冻切片，进行油红O染色；部分冻存于-80℃，测定肝脏中的TG、TC、NEFA、SOD、CAT、GSH-px、MDA水平。NAS评分标准如表1所示。
表1.非酒精性脂肪性肝病活动度积分(NAS)
实验中采用的番茄红素为红色无定型结晶粉末，含量＞95％，购买自上海源叶生物科技有限公司。
1.2试验结果：
(1)肝脏形态和肝脏指数
正常组小鼠肝脏表面颜色普遍鲜红，色泽鲜亮，质地柔软，边缘锐利，无油腻感；MCD组小鼠肝脏颜色稍黄，质地较硬，边缘较圆钝，切面有油腻感，表面有明显的颗粒感；LYC干预组小鼠肝脏在体积、色泽、质地、边缘及切面等方面较模型组均有不同程度的改善。三个实验组小鼠的肝脏指数如图1所述，可以看出，MCD组的肝脏指数与空白组相比明显下降(P<0.01)，而LYC干预组的肝脏指数相比MCD组有所增加(P<0.05)。
(2)肝脏组织切片
图2为肝脏组织切片图(A:HE染色，200×；B:油红O染色，200×；C:Masson纤维染色，200×)。根据图2可以看出，H&E染色显示，MCD导致肝脏中脂质蓄积以及炎症浸润；番茄红素治疗后，脂质蓄积以及炎症浸润均明显减少。油红O染色发现，MCD导致肝脏中脂质蓄积，番茄红素降低肝脏中的脂质蓄积。肝病活动度积分NAS评分结果见表2。
表2.各处理组小鼠肝组织NAS评分比较(n＝6)
注：##P<0.01，与CON组相比；*P<0.05，*P<0.01与MCD组相比
Masson染色得出，MCD导致小鼠肝纤维化的产生，番茄红素降低肝脏的肝纤维化水平。使用Image Jpro软件进行胶原半定量分析显示，番茄红素确实显著降低了肝组织纤维化的程度(P<0.01)。小鼠肝纤维化程度比较结果见表3。
表3.非酒精脂肪性肝炎小鼠肝纤维化程度比较(n＝6)
注：##P<0.01，与CON组相比；*P<0.05，*P<0.01与MCD组相比
(3)肝脏脂质代谢水平
如图3所示，测定肝脏中的TG(甘油三酯)、TC(胆固醇)、NEFA(非酯化脂肪酸)水平发现，MCD导致肝脏中TG、TC、NEFA水平显著升高(P<0.01)；番茄红素治疗后，肝脏TG、TC、NEFA水平显著降低(P<0.05)。以上结果表明，番茄红素改善MCD诱导的脂质代谢紊乱情况。
(4)肝脏氧化应激相关酶系水平
如图4所示，测定小鼠肝脏中SOD(超氧化物歧化酶)、CAT(过氧化氢酶)、GSX-px(谷胱甘肽过氧化物酶)、MDA(丙二醛)含量水平发现，MCD导致肝脏中SOD、CAT、GSX-px水平显著下降(P<0.01)，MDA水平显著增加(P<0.01)；番茄红素治疗后，肝脏SOD、GSX-px和CAT水平显著增加(P<0.01；P<0.05)，MDA显著降低(P<0.01)，接近正常状态。以上结果表明，番茄红素改善MCD诱导的氧化应激水平，恢复线粒体活性氧稳态。
(5)肝脏细胞凋亡水平
图5中小鼠肝脏TUNEL(原位末端转移酶标记)染色结果显示了肝脏细胞凋亡的情况，MCD导致肝脏细胞的大面积凋亡，番茄红素治疗后，凋亡情况有所好转。图6显示了对阳性细胞的半定量分析结果，番茄红素治疗后，肝脏的凋亡细胞数显著降低(P<0.01)。结果表明，番茄红素改善了MCD诱导的肝脏细胞凋亡的情况。
实施例2
采用高脂高胆固醇(HFHC)诱导小鼠的非酒精性脂肪肝炎模型：高脂高胆固醇饮食，又被称为“西方饮食”，喂食这种饮食相比于MCD饮食造模时间更长，但能形成更贴近人体摄食量和体重增加，血清胰岛素水平较高的表型。其诱导的小鼠非酒精性脂肪性肝炎症状，包括单纯脂肪变性、肝炎和肝纤维化，相关的肝脏损伤类似于人类发病机制。
2.1试验方法
(1)动物分组：将6周龄C57BL/6J雄性小鼠(体重18～22g)饲养于标准SPF屏障环境，保持恒温(22℃)、恒湿(55％)、12小时昼夜交替以及自由摄食和饮水。适应性饲养1周后，将24只小鼠平均分为空白对照(CW+C)组、HFHC+C模型组、HFHC+LP3番茄红素低剂量干预组和HFHC+LP6番茄红素高剂量干预组，3组小鼠自由饮水。
(2)给药方法：适应性饲养1周后，HFHC+LP3组和HFHC+LP6小鼠每日给予番茄红素溶液0.25mL(剂量：3mg/kg/day和6mg/kg/day)，番茄红素临使用前用食用玉米油进行溶解；CW+C组与HFHC+C组给予0.25mL食用玉米油，每天灌胃一次，连续给药12周。
(3)模型建立：采用HFHC饲料诱导小鼠非酒精性脂肪肝炎模型，HFHC+C、HFHC+LP3和HFHC+LP6组饲喂HFHC饲料，CW+C组饲喂标准饲料。在试验过程中，每日记录小鼠体重、摄食状态。
(4)组织处理：实验结束后，解剖小鼠。收集新鲜小鼠肝脏，部分浸泡于2.5％戊二醛固定液中，应用超薄切片机进行切片，再经戊二醛和锇酸双重固定，丙酮脱水，环氧树脂包埋，超薄切片，醋酸枸椽酸电子又重染色，透射电镜观察。收集血液，经冷冻离心，取上层血清进行ALT、AST、TC、TG的含量测定。
2.2试验结果
(1)肝脏形态
CW+C空白组小鼠肝脏表面颜色普遍鲜红，色泽鲜亮，质地柔软，边缘锐利，无油腻感；HFHC组小鼠肝脏明显肿大，颜色稍黄，质地较硬，边缘较圆钝，切面有油腻感，表面有明显的颗粒感；HFHC+LP3和HFHC+LP6干预组小鼠肝脏在体积、色泽、质地、边缘及切面等方面较模型组均有不同程度的改善。
(2)脂质代谢指标
与CW+C空白组比较，HFHC+C模型组血清内TC、TG、ALT和AST水平显著升高(P＜0.01)，这表明高脂高胆固醇导致小鼠体内脂质代谢出现紊乱，肝脏出现损伤。与模型组比较，番茄红素高、低浓度组干预能够降低TC、TG、ALT和AST水平(P＜0.01，P＜0.05)，且具有一定的浓度依赖。这表明番茄红素可改善高脂高胆固醇导致的小鼠脂质代谢紊乱，改善肝功能，减轻肝脏损伤。相关结果见表4。
表4.番茄红素对HFHC诱导的非酒精性脂肪肝炎小鼠的血清ALT、AST、TC、TG水平影响
注：##P<0.01，与CW+C组相比；*P<0.05，**P<0.01与HFHC+C组相比
(3)肝组织超微结构的影响
如图7所示，透射电镜下观察到正常组小鼠肝细胞形态正常，膜界清晰，可见微绒毛，细胞质中可见数量较多且形态正常的线粒体、内质网、高尔基复合体、核糖体以及糖原颗粒、微小脂滴等内容物，细胞核形态规则且居中；模型组肝细胞胞浆中弥散数量众多且大小不一的脂质空泡，部分细胞中的线粒体轻度肿胀，内质网扩张；HFHC+LP3和HFHC+LP6干预组小鼠肝细胞内脂滴空泡均有不同程度的减少，线粒体结果趋于正常。
实施例3
采用油酸和棕榈酸诱导HepG2细胞脂质代谢紊乱模型。
3.1试验方法
以油酸和棕榈酸诱导HepG2细胞脂质代谢紊乱模型，探究番茄红素对非酒精性脂肪肝炎线粒体功能障碍的调节作用：
将HepG2细胞接种在DMEM培养基中，在37℃、5％CO2细胞培养箱中培养。取对数生长期HepG2接种于6孔板，HepG2细胞接种后24h，以0.5mM FFA造模液处理24h诱导生成脂质堆积模型，再以50μM浓度番茄红素处理24小时，ROS染色后显微镜观察染色结果；取细胞上清液进行TC、TG测定，使用Trizol试剂提取细胞RNA，用ND5000超微量分光光度计检测RNA质量及浓度，采用试剂盒进行反转录，通过RT-qPCR检测了细胞中BAX、Cas9、PGC1α、PPARα的mRNA的表达量的变化
引物序列：
BAX(AAGAAGCTGAGCGAGTGT；GGAGGAAGTCCAATGTC)
Cas9(CTTCGTTTCTGCGAACTAACAGG；GCACCACTGGGGTAAGGTTT)
PPARα(ATGGTGGACACGGAAAGCC；CGATGGATTGCGAAATCTCTTGG)
PGC-1α(TCTGAGTCTGTATGGAGTGACAT；CCAAGTCGTTCACATCTAGTTCA)
以上引物由北京擎科生物科技有限公司合成。
3.2试验结果
(1)细胞胞内脂质代谢水平
如图8所示，与空白组比较，FFA模型组细胞胞内TC、TG水平显著升高(P＜0.01)；与模型组比较，番茄红素干预组TC、TG水平降低(P＜0.01)。油红O染色结果如图9所示，可以看出，油酸和棕榈酸共刺激后，HepG2细胞内出现大量的红色脂滴聚集，环绕细胞膜一周呈圆形分布。番茄红素可减轻细胞脂质蓄积。以上结果表明番茄红素可改善HepG2细胞脂质代谢紊乱，改善肝功能。
(2)细胞胞内氧化应激水平
如图10-11所示，与空白组比较，FFA模型组细胞胞内氧化应激水平显著升高，ROS含量激增(P＜0.01)；与模型组比较，番茄红素干预组ROS水平降低(P＜0.01)。表明番茄红素可改善HepG2细胞氧化应激紊乱的情况，改善线粒体功能。
(3)细胞线粒体膜电势水平
如图12所示，与空白组比较，FFA模型组细胞线粒体膜电势水平有所下降，而番茄红素干预组促进线粒体膜电势水平升高，产生的能量和ATP增多，促进细胞能量转换。结果表明番茄红素可改善HepG2线粒体功能。
(4)凋亡和线粒体调控相关基因的表达
如图13所示，进一步分析肝脏凋亡和线粒体调控相关基因发现，FFA模型组导致肝脏凋亡相关基因BAX和Cas9的显著增加(P＜0.05；P＜0.01)；番茄红素干预组降低了肝脏细胞凋亡基因的表达(P＜0.05)。PGC-1α是重要的转录共激活因子，是线粒体生物合成和能量代谢的中心诱导剂，刺激PGC-1α的表达可以调控线粒体功能，与PPAR通路的激活有关。相比空白组，FFA模型组增加了PGC-1α和PPARα的显著增加(P＜0.05)，这可能是相比正常状态，线粒体增加了对脂质的代谢，线粒体的能量调控功能被激活；番茄红素干预组相比模型组更加增加了PGC-1α和下游PPARα的表达(P＜0.05)，促进了线粒体的能量代谢，有助于非酒精脂肪性肝炎症状的改善。
实施例4
在保证番茄红素为主要活性成分的基础上，通过加入食品添加剂等开发感官品质符合广大市场消费者需求的番茄红素片剂和液体补充剂，并验证其对炎症性肠病的预防和保护效果。
4.1试验方法
番茄红素片剂的制作：称取10％番茄红素粉末、55％淀粉、35％β-环糊精，将上述材料混匀后，用80％乙醇溶液喷洒后造粒，55℃干燥3h后，过筛。取20～40目之间的颗粒作为压片材料置于压片机内，在15kN～20kN下压片，制得0.5g片剂；
番茄红素液态补充剂购买自上海逸古食品有限公司
以MCD诱导的小鼠非酒精性脂肪肝炎为研究模型，探究不同番茄红素的补充对非酒精性脂肪肝炎的影响，模型建立如下：
(1)动物分组：将6周龄C57BL/6J雄性小鼠(体重18～22g)饲养于标准SPF屏障环境，保持恒温(22℃)、恒湿(55％)、12小时昼夜交替以及自由摄食和饮水。适应性饲养1周后，将18只小鼠平均分为疾病模型(MCD)组、番茄红素片剂组(LP+MCD)组和番茄红素液态补充剂组(LJ+MCD)组，自由饮水。
(2)给药方法：将番茄红素片剂压碎制成粉末，使用0.35mL 0.9％氯化钠溶液混匀，灌胃给LP+MCD组小鼠；LJ+MCD组小鼠每日给予番茄红素溶液0.35mL(不同补充方式中番茄红素剂量：6mg/kg/day)，MCD组小鼠灌胃0.9％氯化钠溶液，每天灌胃一次，连续给药6周，小鼠饮用正常饮水。
(3)模型建立：采用MCD饲料诱导小鼠非酒精性脂肪肝炎模型，MCD模型组、LP+MCD组和LJ+MCD饲喂MCD饲料，在试验过程中，每日记录小鼠体重、摄食状态。
(4)组织处理：实验结束后，解剖小鼠。收集新鲜小鼠肝脏，部分浸泡于10％福尔马林中，进行H&E染色、天狼星红染色和TUNEL染色；部分直接制备冷冻切片，进行油红O染色；部分冻存于-80℃，测定肝脏中的TG、TC、NEFA、SOD、CAT、GSH-px、MDA水平。
4.2实验结果
与MCD疾病模型组小鼠相比，饲喂番茄红素片剂和液体补充剂的小鼠的非酒精性脂肪肝炎症状相关的症状如肝脏损伤减弱、脂质沉积减少、氧化应激酶系水平增加、肝脏细胞凋亡减少，说明不同形式番茄红素补充可显著抵抗MCD饮食诱导的小鼠非酒精性脂肪肝炎症状。
以上所述仅是本发明的优选实施方式，应当指出的是，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，所述非酒精性脂肪肝炎症状由肝细胞线粒体功能障碍引起，其特征在于，所述肝细胞线粒体功能障碍包括：肝细胞凋亡数量增加、氧化应激水平升高、脂质代谢紊乱或线粒体形态肿胀。
2.根据权利要求1所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述产品包括药物、膳食补充剂、食品或饮料。
3.根据权利要求1所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述非酒精性脂肪肝炎症状包括：肝纤维化、肝脏肿大硬化、肝内脂质沉积或血脂升高。
4.根据权利要求1所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述脂质代谢紊乱包括胆固醇含量升高、甘油三酯含量升高和非酯化脂肪酸含量升高；所述氧化应激水平升高包括超氧化物歧化酶水平降低、过氧化氢酶水平降低、谷胱甘肽过氧化物酶水平降低或丙二醛水平升高。
5.根据权利要求1所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述番茄红素的分子式为C40H56，所述番茄红素的分子结构包括反式番茄红素或顺式番茄红素中的一种或几种。
6.根据权利要求5所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述反式番茄红素为全反式番茄红素；所述顺式番茄红素包括15顺式番茄红素、13顺式番茄红素、11顺式番茄红素、9顺式番茄红素、7顺式番茄红素或5顺式番茄红素中的一种或几种。
7.根据权利要求1所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述产品中还包含药学上或食品上可接受的载体或辅料。
8.根据权利要求7所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述药学上或食品上可接受的辅料包括稀释剂、赋形剂、填充剂、粘合剂、润湿剂、崩解剂、吸收促进剂、表面活性剂、吸附剂或润滑剂。
9.根据权利要求7所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述药学上或食品上可接受的载体包括片剂、散剂、丸剂、注射剂、胶囊剂、膜剂、栓剂、膏剂或冲剂。
10.根据权利要求7所述的番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用，其特征在于，所述产品通过注射、喷射、滴鼻、滴眼、渗透或摄入的方法导入机体。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211294188.6A CN115554281A (zh) | 2022-10-21 | 2022-10-21 | 番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211294188.6A CN115554281A (zh) | 2022-10-21 | 2022-10-21 | 番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115554281A true CN115554281A (zh) | 2023-01-03 |
Family
ID=84746220
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211294188.6A Pending CN115554281A (zh) | 2022-10-21 | 2022-10-21 | 番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115554281A (zh) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090318567A1 (en) * | 2006-04-13 | 2009-12-24 | Cammedica Limited | Lycopene for the treatment of metabolic dysfunction |
| CN111714561A (zh) * | 2020-07-23 | 2020-09-29 | 赵晓娟 | 番茄茎叶提取物在治疗酒精诱导肝损伤中的应用 |
-
2022
- 2022-10-21 CN CN202211294188.6A patent/CN115554281A/zh active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090318567A1 (en) * | 2006-04-13 | 2009-12-24 | Cammedica Limited | Lycopene for the treatment of metabolic dysfunction |
| CN111714561A (zh) * | 2020-07-23 | 2020-09-29 | 赵晓娟 | 番茄茎叶提取物在治疗酒精诱导肝损伤中的应用 |
Non-Patent Citations (4)
| Title |
|---|
| JELENA MUSTRA RAKIC等: "Dietary lycopene attenuates cigarette smoke-promoted nonalcoholic steatohepatitis by preventing suppression of antioxidant enzymes in ferrets", JOURNAL OF NUTRITIONAL BIOCHEMISTRY, vol. 91 * |
| YINHUA NI等: "Lycopene prevents the progression of lipotoxicity-induced nonalcoholic steatohepatitis by decreasing oxidative stress in mice", FREE RADICAL BIOLOGY AND MEDICINE, vol. 152, pages 571, XP086158439, DOI: 10.1016/j.freeradbiomed.2019.11.036 * |
| 赵家军等: "《系统内分泌学 下》", 中国科学技术出版社, pages: 3 - 4 * |
| 魏来等: "番茄红素对大鼠非酒精性脂肪肝的作用研究", 中国药业, vol. 19, no. 03, pages 3 - 5 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | The biological activity mechanism of chlorogenic acid and its applications in food industry: A review | |
| EP2206509B1 (en) | Method of producing aloe vera extract | |
| Yang et al. | Apple polyphenols modulates the antioxidant defense response and attenuates inflammatory response concurrent with hepatoprotective effect on grass carp (Ctenopharyngodon idellus) fed low fish meal diet | |
| Wang et al. | Inhibitory effects of Dendrobium candidum Wall ex Lindl. on azoxymethane‑and dextran sulfate sodium‑induced colon carcinogenesis in C57BL/6 mice | |
| KR20160041138A (ko) | 갈색거저리 유충의 추출물 또는 갈색거저리 유충의 현탁액을 유효성분으로 포함하는 비만 예방 또는 치료용 조성물 | |
| Luo et al. | Biological Potential and Mechanisms of Tea’s Bioactive Compounds in Tea: An Updated Review | |
| CN114028533A (zh) | 一种具有解酒保肝功能的组合物及其制备方法和应用 | |
| Yoo et al. | Crepidiastrum denticulatum extract protects the liver against chronic alcohol-induced damage and fat accumulation in rats | |
| EP3146976B1 (en) | Pharmaceutical composition for preventing or treating macular degeneration, containing natural mixture extract as active ingredient | |
| KR101887631B1 (ko) | 삼백초 성분인 사우치논을 유효성분으로 함유하는 노화지연, 수명연장, 또는 리포푸신 축적으로 인한 질환의 예방, 치료 또는 개선용 조성물 | |
| RU2351340C2 (ru) | Лекарственное средство и пищевой продукт или напиток для улучшения функций поджелудочной железы | |
| CN115554281A (zh) | 番茄红素在制备改善非酒精性脂肪肝炎症状的产品中的应用 | |
| Glick | Modes of action of gallic acid in suppressing food intake of rats | |
| EP3117825A1 (en) | Oral formulation comprising berberine and morus alba extract | |
| KR20110061108A (ko) | 흰민들레 추출물을 유효성분으로 함유하는 간암 예방 또는 치료용 조성물 | |
| US9937220B2 (en) | Anti-diabetic nutraceutical composition from palm leaf extract | |
| Soliman et al. | Hepatoprotective effect of carnosine on liver biochemical parameters in chronic ethanol intoxicated rat | |
| KR20150091770A (ko) | 옥덩굴 추출물을 포함하는 비만 치료 또는 예방용 조성물 | |
| CN109908152B (zh) | 一种防控对乙酰氨基酚所致肝损伤的药物及其应用 | |
| KR20200000174A (ko) | 두메부추 추출물을 포함하는 간 섬유화 또는 간경화 예방, 개선 또는 치료용 조성물 | |
| CN111632060B (zh) | 一种含黄芩苷和二甲双胍的组合物及其制备方法与应用 | |
| KR102451161B1 (ko) | 무궁화 추출물을 유효성분으로 포함하는 간 건강 개선 및 보호용 조성물 | |
| JP4879520B2 (ja) | 肝線維化抑制剤 | |
| KR20240094564A (ko) | 메틸 리놀레산을 포함하는 지방간 질환의 개선, 예방 또는 치료용 약학적 조성물 | |
| KR20240061958A (ko) | Ver-246608을 포함하는 지방간 질환 예방 또는 치료용 약학적 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20230103 |
|
| RJ01 | Rejection of invention patent application after publication |