CN112791089A - Experimental method for influence of ellagic acid and autophagy inhibitor on aging of mouse model - Google Patents
Experimental method for influence of ellagic acid and autophagy inhibitor on aging of mouse model Download PDFInfo
- Publication number
- CN112791089A CN112791089A CN202110085946.2A CN202110085946A CN112791089A CN 112791089 A CN112791089 A CN 112791089A CN 202110085946 A CN202110085946 A CN 202110085946A CN 112791089 A CN112791089 A CN 112791089A
- Authority
- CN
- China
- Prior art keywords
- group
- aging
- ellagic acid
- mice
- mouse
- 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.)
- Granted
Links
- AFSDNFLWKVMVRB-UHFFFAOYSA-N Ellagic acid Chemical compound OC1=C(O)C(OC2=O)=C3C4=C2C=C(O)C(O)=C4OC(=O)C3=C1 AFSDNFLWKVMVRB-UHFFFAOYSA-N 0.000 title claims abstract description 107
- 229920002079 Ellagic acid Polymers 0.000 title claims abstract description 79
- ATJXMQHAMYVHRX-CPCISQLKSA-N Ellagic acid Natural products OC1=C(O)[C@H]2OC(=O)c3cc(O)c(O)c4OC(=O)C(=C1)[C@H]2c34 ATJXMQHAMYVHRX-CPCISQLKSA-N 0.000 title claims abstract description 79
- 229960002852 ellagic acid Drugs 0.000 title claims abstract description 79
- 235000004132 ellagic acid Nutrition 0.000 title claims abstract description 79
- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 238000002474 experimental method Methods 0.000 title claims abstract description 71
- 230000032683 aging Effects 0.000 title claims abstract description 46
- 239000012822 autophagy inhibitor Substances 0.000 title claims abstract description 34
- 238000010172 mouse model Methods 0.000 title claims abstract description 15
- 241000699670 Mus sp. Species 0.000 claims abstract description 62
- 239000003814 drug Substances 0.000 claims abstract description 25
- 238000012347 Morris Water Maze Methods 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 11
- 230000035617 depilation Effects 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 50
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 claims description 42
- 229960003677 chloroquine Drugs 0.000 claims description 33
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 claims description 33
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 32
- 230000000694 effects Effects 0.000 claims description 31
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 29
- 229960003105 metformin Drugs 0.000 claims description 19
- 230000009182 swimming Effects 0.000 claims description 19
- 238000012360 testing method Methods 0.000 claims description 19
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 claims description 17
- 239000013641 positive control Substances 0.000 claims description 16
- 235000012631 food intake Nutrition 0.000 claims description 14
- 230000037406 food intake Effects 0.000 claims description 10
- 201000004384 Alopecia Diseases 0.000 claims description 9
- 208000024963 hair loss Diseases 0.000 claims description 9
- 239000007924 injection Substances 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 9
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000003203 everyday effect Effects 0.000 claims description 6
- 230000003752 improving hair Effects 0.000 claims description 6
- 239000007928 intraperitoneal injection Substances 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 230000037396 body weight Effects 0.000 claims description 4
- 238000011666 aging animal model Methods 0.000 claims description 3
- 230000003676 hair loss Effects 0.000 claims description 3
- 239000002504 physiological saline solution Substances 0.000 claims description 3
- 239000004408 titanium dioxide Substances 0.000 claims description 3
- 230000003442 weekly effect Effects 0.000 claims description 3
- 230000003542 behavioural effect Effects 0.000 claims description 2
- 230000004807 localization Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 230000003712 anti-aging effect Effects 0.000 abstract description 10
- 238000012827 research and development Methods 0.000 abstract description 4
- 238000012795 verification Methods 0.000 abstract description 2
- 238000011835 investigation Methods 0.000 abstract 1
- 230000002829 reductive effect Effects 0.000 description 13
- 230000004900 autophagic degradation Effects 0.000 description 10
- 230000002951 depilatory effect Effects 0.000 description 8
- 230000002035 prolonged effect Effects 0.000 description 5
- 230000007087 memory ability Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000012549 training Methods 0.000 description 4
- 235000014360 Punica granatum Nutrition 0.000 description 3
- 229920000241 Punicalagin Polymers 0.000 description 3
- ZJVUMAFASBFUBG-OGJBWQGYSA-N punicalagin Chemical compound C([C@H]1O[C@@H]([C@@H]2OC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)O[C@H]2[C@@H]1OC(=O)C1=CC(O)=C(O)C(O)=C11)O)OC(=O)C2=CC(O)=C(O)C(O)=C2C2=C(O)C(O)=C(OC3=O)C4=C2C(=O)OC2=C4C3=C1C(O)=C2O ZJVUMAFASBFUBG-OGJBWQGYSA-N 0.000 description 3
- LMIBIMUSUFYFJN-RSVYENFWSA-N punicalagin Natural products O[C@@H]1O[C@@H]2COC(=O)c3cc(O)c(O)c(O)c3c4c(O)cc5OC(=O)c6c(c(O)c(O)c7OC(=O)c4c5c67)c8c(O)c(O)c(O)cc8C(=O)O[C@H]2[C@@H]9OC(=O)c%10cc(O)c(O)c(O)c%10c%11c(O)c(O)c(O)cc%11C(=O)O[C@@H]19 LMIBIMUSUFYFJN-RSVYENFWSA-N 0.000 description 3
- ZRKSVMFLACVUIU-UHFFFAOYSA-N punicalagin isomer Natural products OC1=C(O)C(=C2C3=4)OC(=O)C=4C4=C(O)C(O)=C3OC(=O)C2=C1C1=C(O)C(O)=C(O)C=C1C(=O)OC1C2OC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(O)OC1COC(=O)C1=CC4=C(O)C(O)=C1O ZRKSVMFLACVUIU-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- CUXYLFPMQMFGPL-BGDVVUGTSA-N (9Z,11E,13Z)-octadecatrienoic acid Chemical compound CCCC\C=C/C=C/C=C\CCCCCCCC(O)=O CUXYLFPMQMFGPL-BGDVVUGTSA-N 0.000 description 2
- 241000219991 Lythraceae Species 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229940126904 hypoglycaemic agent Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 230000009758 senescence Effects 0.000 description 2
- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- RDFLLVCQYHQOBU-GPGGJFNDSA-O Cyanin Natural products O([C@H]1[C@H](O)[C@H](O)[C@H](O)[C@H](CO)O1)c1c(-c2cc(O)c(O)cc2)[o+]c2c(c(O[C@H]3[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O3)cc(O)c2)c1 RDFLLVCQYHQOBU-GPGGJFNDSA-O 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 206010024642 Listless Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 244000294611 Punica granatum Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000004378 air conditioning Methods 0.000 description 1
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical group C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000004957 autophagosome Anatomy 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- RDFLLVCQYHQOBU-ZOTFFYTFSA-O cyanin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=[O+]C1=CC(O)=C2)C=3C=C(O)C(O)=CC=3)=CC1=C2O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 RDFLLVCQYHQOBU-ZOTFFYTFSA-O 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000009097 homeostatic mechanism Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000017971 listlessness Diseases 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 235000018770 reduced food intake Nutrition 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- CUXYLFPMQMFGPL-UYWAGRGNSA-N trichosanic acid Natural products CCCCC=C/C=C/C=CCCCCCCCC(=O)O CUXYLFPMQMFGPL-UYWAGRGNSA-N 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
Abstract
The invention discloses an experimental method for the influence of ellagic acid combined with an autophagy inhibitor on the aging of a mouse model, which randomly divides experimental mice into 6 groups, carries out administration in the process of constructing the aging model of the experimental mice, and then adopts a Morris water maze experiment to carry out experimental investigation on the aging condition of the mice. The experimental method can effectively investigate the influence of the ellagic acid and the ellagic acid combined autophagy inhibitor on aging from indexes such as memory, depilation (hair) and the like, and can provide experimental support and verification for the research and development of the anti-aging drugs of the ellagic acid and the ellagic acid combined autophagy inhibitor.
Description
Technical Field
The invention relates to the technical field of experiments, in particular to an experiment method for influence of ellagic acid combined autophagy inhibitor on aging of a mouse model.
Background
Aging is a biological process in which all individuals in nature are influenced by genetic factors and internal and external environments, and is irreversible, but can intervene to delay aging. There are several theories on the mechanisms of senescence that autophagy plays an important role in the progression of senescence. Autophagy is a homeostatic mechanism by which cells maintain homeostasis, clearing harmful substances (misfolded protein aggregates, pathogens, senescent organelles), and regenerating beneficial substances for cell recycling. In previous researches, autophagy is proved to be involved in pathogenesis of diseases related to aging, and the increase of autophagy level of a body can reduce the deposition of Abeta 1-42, thereby playing a role in delaying or improving cognitive dysfunction. However, in recent years, it has been found that massive neuronal death in C1 region of hippocampus of rats, which is reperfusion due to artery occlusion in brain, is associated with excessive activation of autophagy. Autophagy can be seen to have a dual role.
Ellagic Acid (EA) is widely present in plant tissues such as various soft fruits, nuts, etc. as a natural polyphenol dilactone. Modern pharmacological research shows that ellagic acid has the effects of resisting oxidation, resisting tumor, inhibiting bacteria and the like. The studies on the scavenging of oxygen free radicals in EA body are more, but the studies on the aging-causing effect of D-galactose and the anti-aging effect of the combined autophagy inhibitor are not reported in detail.
Therefore, the invention provides an experimental method for the influence of the ellagic acid combined with the autophagy inhibitor on the aging of a mouse model, so as to provide scientific basis for the research and development of anti-aging drugs.
Disclosure of Invention
Therefore, the invention provides an experimental method for the influence of the ellagic acid and the ellagic acid combined autophagy inhibitor on the aging of a mouse model, and aims to research the effect of the ellagic acid and the ellagic acid combined autophagy inhibitor on the anti-aging aspect and provide a scientific basis for the research and development of anti-aging drugs.
The technical scheme of the invention is as follows:
an experimental method for the influence of ellagic acid combined with an autophagy inhibitor on aging of a mouse model comprises the following experimental steps:
s1: randomly selecting a plurality of mice, and randomly dividing the mice into 6 groups, namely a blank control group, an aging group, a positive control group, an Ellagic Acid (EA) group, an autophagy inhibitor group and a combined medicine group;
s2: adopting a D-galactose induced subacute aging method, injecting a 5% D-galactose solution into the mice of the blank control group subcutaneously on the neck and the back every day, continuously injecting for 42 days, constructing an aging animal model, simultaneously, administering the mice of the positive control group, the Ellagic Acid (EA) group, the autophagy inhibitor group and the combined drug group, performing intragastric lavage on the blank control group, and injecting physiological saline into the neck subcutaneously;
during the injection and administration period, the body weight of the mouse is measured and recorded every week, the water intake and the food intake of the mouse are measured and recorded every week, statistical treatment is carried out through statistical software, and differences of all groups are observed;
during the injection and administration, the depilation status of the mice was recorded weekly and the mice were photographed and recorded periodically, and then the size of the depilation area of the mice after each group of 42d was calculated by the image analysis software and compared.
S3: after injection and administration are finished, performing continuous Morris water maze experiments on all mice from day 2, wherein the water maze experiments comprise a positioning navigation experiment and a space exploration experiment; the space exploration experiment is after the positioning voyage experiment.
Further, the Morris water maze test of step S3 is performed for 6 days, the positioning navigation test is continuously performed for the first 5 days, and the space exploration test is performed for the 6 th day.
Further, in step S2, the positive control group is administered by metformin lavage, the Ellagic Acid (EA) group is ellagic acid lavage, the autophagy inhibitor group is chloroquine intraperitoneal injection, and the combined drug group is ellagic acid lavage and chloroquine intraperitoneal injection.
Further, in the Morris water maze experiment of step S3, all mice were moved into the room of the behavioural experiment 1 hour before the experiment every day to adapt to the environment of the room; the Morris water maze experiment adopts a Morris water maze experiment instrument, the Morris water maze experiment instrument comprises a movable platform and a water pool, the bottom and the periphery of the wall of the water pool are dyed into white, and a certain amount of titanium dioxide is poured into clear water in the water pool in advance to conceal the platform; a camera connected with a computer is arranged right above the water pool to record the complete swimming track of the mouse in a certain time, and the total swimming distance, time, swimming speed, the time required for finding the platform and the like of the mouse are automatically calculated.
Further, the positioning navigation experiment is performed 1 time each in the morning and afternoon every day, and the experiment operation is as follows: respectively putting the mouse into water from 1 fixed water entry point facing the pool wall, starting timing while putting the mouse into the water, observing and recording the time required by the mouse to find an underwater hidden platform, wherein the result is the escape latency; if the platform is not found successfully within 60s, the experimenter guides the mouse to a platform hidden under water, keeps standing for 15s on the platform to observe the surrounding environment, and records the latency as 60 s.
Further, the experimental operation of the space exploration experiment is as follows: the platform hidden in the water is removed, any position in the fixed water pool is used as a water entry point of the experiment, the mouse swims in the water pool to explore and search the platform for 60s, and the escape latency, the swimming speed, the total swimming time of the quadrant where the original platform is located and the times of crossing the position of the original platform during the experiment are recorded.
Further, the ellagic acid is pomegranate ellagic acid.
Further, the image analysis software in step S2 is imageprocess.
The invention also provides application of the metformin to preparation of a medicament for preventing and improving hair loss, wherein the hair loss is mainly caused by aging.
The invention also provides a new application of chloroquine in preparing a medicament for preventing and improving hair loss, wherein the hair loss is mainly caused by aging.
Further, the chloroquine and the ellagic acid are compounded and applied to preparing the anti-aging drugs, and are particularly applied to preventing and improving hair loss.
By adopting the technical scheme, the beneficial effects are as follows:
the experimental method can effectively investigate the influence of the ellagic acid and the ellagic acid combined autophagy inhibitor on aging from indexes such as memory, depilation (hair) and the like, and can provide experimental support and verification for the research and development of the anti-aging drugs of the ellagic acid and the ellagic acid combined autophagy inhibitor.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a comparative graph of swimming latency of mice in a localized voyage experiment according to an embodiment of the present invention;
FIG. 2 shows how many times a mouse crosses an escape platform and an effective area in a spatial exploration experiment according to an embodiment of the present invention;
FIG. 3 shows the latency of mice in a space exploration experiment according to an embodiment of the present invention;
FIG. 4 is a diagram of mouse swimming trajectories in a space search experiment according to an embodiment of the present invention, wherein A: blank control group; b: aging group C: ellagic acid group D: combination group E: autophagy inhibitor F: a positive control group;
FIG. 5 shows the unhairing condition of a mouse in the present invention, which is composed of a blank control group, an aging model group, a positive control group, an Ellagic Acid (EA) group, an autophagy inhibitor group, and a combination group in sequence from top to bottom;
FIG. 6 is a histogram comparing the depilated area of a mouse in accordance with an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. Those used in the following examples, which are not specifically indicated, were carried out according to the conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example (b): the example provides an experimental method for the influence of the ellagic acid combined autophagy inhibitor on the aging of a mouse model, which comprises the following steps:
s1: selecting 48 healthy and clean Kunming mice with age of 1 month, female body weight (24+2) g, randomly dividing the mice into a blank control group, an aging group, a positive control group, an Ellagic Acid (EA) group, an autophagy inhibitor group and a combined drug group, wherein each group comprises 8 mice, and the experimental mice are purchased from the experimental animal center of Xinjiang medical university. Freely drinking tap water, feeding in independent mouse cage feeding box, filtering and purifying air, and air-conditioning at room temperature of 26-28 deg.C.
S2: adopting a D-galactose induced subacute aging method, injecting a 5% D-galactose solution (1000mg/Kg) into the mice except a blank control group subcutaneously on the neck and back every day, continuously injecting for 42 days to construct an aging animal model, and simultaneously, administering the mice of a positive control group, an Ellagic Acid (EA) group, an autophagy inhibitor group and a combined drug group, wherein the blank control group is subjected to gastric lavage and the neck is injected with physiological saline with equal quantity subcutaneously; the administration mode of the positive control group is to perform intragastric administration of metformin (50 mg/kg. d), the administration mode of the Ellagic Acid (EA) group is intragastric administration of ellagic acid (50 mg/kg. d), the administration mode of the autophagy inhibitor group is intraperitoneal injection of chloroquine (50 mg/kg. 3d), and the combined medicine group is intraperitoneal injection of ellagic acid (50 mg/kg. d) and chloroquine (50 mg/kg. 3 d).
During the injection and administration period, the body weight of the mice is measured and recorded every week, the water intake (see table 2) and the food intake (see table 3) of the mice are measured and recorded every week, statistical treatment is carried out through SPSS25.0 statistical software, and differences of each group are observed;
during the injection and administration, the depilation status of the mice was recorded weekly, and photographed at 4d, 31d, 42d (see fig. 5), and then the size of the depilation area of the mice after each group 42d was calculated by imageplus 6.0 image analysis software and compared (see fig. 6).
In the step, D- (+) -galactose (D-gal) is administrated from Jiangsu Peng Xiang biological medicine, Inc., Metformin (MF) is administrated from Beijing Jingfeng pharmaceutical group, punica granatum Ellagic Acid (EA) is purchased from Shanghai Michelin Biotechnology, Inc., Chloroquine (CQ) is purchased from Wuhandinghui biological chemical, Inc., and electronic balance (Shanghai Cyanin instruments, Inc.).
S3: after injection and administration are finished, performing continuous Morris water maze experiments on all mice from day 2, wherein the water maze experiments comprise a positioning navigation experiment and a space exploration experiment; the space exploration experiment is after the positioning voyage experiment. Before the experiment every day, all mice are moved into a room of the ethological experiment 1 hour in advance to adapt to the environment of the room; the Morris water maze experiment adopts a Morris water maze experiment instrument, the Morris water maze experiment instrument comprises a movable platform and a water pool, the bottom and the periphery of the wall of the water pool are dyed into white, and a certain amount of titanium dioxide is poured into clear water in the water pool in advance to conceal the platform; a camera connected with a computer is arranged right above the water pool to record the complete swimming track of the mouse in a certain time, and the total swimming distance, time, swimming speed, the time required for finding the platform and the like of the mouse are automatically calculated.
After the mice are continuously dosed for 42 days, the learning capacity of the animals is inspected through a Morris water maze experiment, namely a positioning navigation experiment, the mice are trained 2 times per day, 1 time is respectively carried out in the morning and the afternoon, the mice are respectively put into water from 1 fixed water entry point facing the pool wall, the timing is started when the mice are put into the water, the time required for finding the underwater hidden platform by the mice is observed and recorded, and the result is the escape latency. If the platform is not found successfully within 60s, the experimenter guides the mouse to a platform hidden under water, keeps standing for 15s on the platform to observe the surrounding environment, and records the latency as 60 s.
After the mouse completes the positioning navigation experiment for 5 days before, on the 6 th day, the platform hidden in the water is removed, any position in the fixed water pool is used as a water inlet point of the experiment, the mouse swims in the water pool to explore and search the platform for 60s, the escape latency, the swimming speed, the total swimming time of the quadrant where the original platform is located and the number of times of passing through the position where the original platform is located during the experiment are recorded, and the experiment result is shown in the figure 1, the figure 2 and the figure 3.
Wherein, SPSS25.0 statistical software package is adopted for statistical processing, and the test level alpha is 0.05. The average number between the groups is compared by adopting one-factor variance analysis, the two groups are compared by adopting t test, and the difference with P <0.05 has statistical significance.
The experimental results are as follows:
(1) pomegranate ellagic acid Activity observation of Experimental mice (see Table 1)
Beginning at week 3, the aging group (M) had fewer active counts and decreased activity compared to the placebo group (C); the ellagic acid group (ellagic acid intervention group, EA) was more active than the aging group (M), and the activity was increased; compared with the ellagic acid group (EA), the combined medicine group (EA + CQ) has less active number and activity degree; the Ellagic Acid (EA) group was similar in activity and number of the groups compared to the positive control group (MF), as shown in Table 1.
Table 1: effect of group administration on the Activity of Experimental mice
Note: + means the mice are still; + indicates that the mouse is walking slowly; the + + + mice walked rapidly back and forth.
In the table, group C is a blank control group, group M is an aging group, EA is an ellagic acid group, EA + CQ is a combined drug group, MF is a positive control group, and CQ is an autophagy inhibitor group.
(2) Effect of punicalagic acid on Water intake in laboratory mice (see Table 2)
Starting at week 5, the water intake of the four administration groups (EA, EA + CQ, CQ, MF) was significantly higher than that of the M group (P <0.01) and the difference in water intake between the administration groups was small (P >0.05) compared to the M group; the EA + CQ, CQ group water intake was slightly reduced compared to the EA group, beginning at week 6, and no significant difference was seen between the EA group and the MF group.
Table 2: effect of EA on Water intake in Experimental mice: (
ml/only, day)
Note: in comparison with the set of M,*P<0.05,**P<0.01; in comparison to the group of EAs,#P<0.05，##P<0.01，###P<0.001; in comparison to the set of CQ's,▲P<0.05，▲▲P<0.01，▲▲▲P<0.001；
(3) effect of punicalagin on the food intake of laboratory mice (see Table 3)
Food intake was reduced in all other groups (P <0.05) and the difference between the administration groups was not large (P >0.05) compared to the placebo group (group C) starting at week 3; decreased food intake in the senescent group (group M) compared to group C, starting at week 6; compared with the group M, the food intake of the ellagic acid group (group EA) is slightly increased, and the food intake of the CQ group, especially the group MF and the group EA + CQ is obviously reduced; the combined drug group (EA + CQ group), CQ group and MF group have reduced food intake compared with the EA group; the EA group had increased food intake compared to the positive control group (MF group).
TABLE 3 Effect of EA on food intake in aging mice: (
g/only)
Note: comparison with group C○P<0.05,○○P<0.01, compared to the group M,*P<0.05,**P<0.01，***P<0.001; in comparison to the group of EAs,#P<0.05，##P<0.01; compared with the MF group,▲P<0.05，▲▲P<0.01，▲▲▲P<0.001；
(4) morris Water maze test results
Navigation experimental results (see table four and figure 1)
As training time was extended, the time for each group of mice to find the platform was gradually shortened. Compared with the blank control group (group C), the mice in the aging group (group M) found that the platform latency is obviously prolonged on the 4 th (P <0.05) and 5 th (P <0.01) training days; compared with the aging group (M group), on the 3 rd day of training, the platform latency period found by the mice in the ellagic acid group (EA group) is obviously shortened (P is less than 0.05), and the improvement effect is firstly shown, on the 5 th day of training, the platform latency period found by the mice in the ellagic acid group (EA group) and the mice in the chloroquine group (CQ group) is obviously shortened, and the platform latency period has statistical difference (P is less than 0.05); compared with the EA group, the combined medicine group (EA + CQ group) and the MF group have prolonged latency, and EA is superior to MF in the aspect of improving brain localization.
TABLE 4 influence of EA on aging model mouse latency in positional sailing experiments: (
S)
Note: comparison with group C○P<0.05,○○P<0.01, comparison with group M, P<0.05,**P<0.01; in comparison with the MF group,#P<0.05，##P<0.01，###P<0.001; in comparison to the set of CQ's,▲P<0.05，▲▲P<0.01；
② experimental results of space search (see Table 5, FIG. 2, FIG. 3, FIG. 4)
Compared with the normal group, the mice of the aging group (M group) have obviously prolonged retention time (P is less than 0.01) in the quadrant where the platform is positioned, reduced frequency of passing through the original platform (P is less than 0.05) and short swimming distance, compared with the M group, the retention time (P is less than 0.01) of the EA and CQ group in the quadrant where the platform is positioned is obviously shortened, the swimming distance is prolonged, and the EA and CQ and MF groups have no obvious difference. In the EA group, CQ latency was reduced and the number of crossing the escape platform was increased compared to the positive control group (MF group), as detailed in table 5, fig. 2,3, and 4.
TABLE 5 Effect of EA on latency and crossing times in space exploration experiments in aging mice: (
S)
Note: comparison with group C○P<0.05,○○P<0.01; comparison with M groups*P<0.05,**P<0.01; in comparison to the group of EAs,#P<0.05，##P<0.01; in comparison with the MF group,▲P<0.05，▲▲P<0.01。
(5) effect on depilatory area of Experimental mice (see Table 6, FIG. 5, FIG. 6)
During the continuous administration period of the experimental mice, the mice were observed at 4d, 31d and 42d, and the size of the hair removal area of the mice after 42d administration was calculated and compared by imageplus 6.0 analysis software, and the conditions of each group are detailed in table 6.
TABLE 6 EA Effect on the depilatory area of aging mice: (
mm2)
Note: comparison with group C○P<0.05,○○P<0.01，○○○P<0.001; in comparison with the set of M,*P<0.05,**P<0.01，***P<0.001; in comparison to the group of EAs,#P<0.05，##P<0.01; in comparison with the MF group,▲P<0.05，▲▲P<0.01；
table 6 was analyzed, and after 42d, the depilatory area was significantly enlarged (P <0.001) in the aging group (M group) compared to the blank control group (C group), and the depilatory area was significantly reduced (P <0.001) in the EA group, CQ group, MF group, and EA + CQ group (P <0.01) compared to the M group. The depilatory area of the EA + CQ group was increased compared with that of the EA group, and the depilatory area of the EA group was not distinguished from that of the MF group, and the depilatory area of the CQ group was significantly reduced.
Metformin (CQ), as a commonly used hypoglycemic agent in clinical practice, may also exert anti-aging effects by reducing Reactive Oxygen Species (ROS) production, alleviating DNA damage, activating AMPK, inhibiting mTOR effects, and activating autophagy. Chloroquine is a clinical antimalarial drug and is also widely applied to autophagy research as an autophagy inhibitor. It inhibits autophagy by raising the in vivo pH of the lysosome, preventing the binding of autophagosomes to lysosomes.
Through the experimental method, the food consumption and the activity of the mice are observed, and compared with a blank control group, the food consumption and the activity of an aging group are obviously reduced, indicating that the food consumption is obviously reduced due to aging, listlessness, slow movement and obvious reduction. Compared with the aged group, the activity and food consumption of the administered group are increased. By way of example, it is evident that punicic acid significantly increased the level of activity in model mice, and was not statistically significantly different from the autophagy inhibitor chloroquine (P > 0.05). The results show that the punicalagin has the function of improving the activity of the mice, and the activity of the punicalagin is probably related to the inhibition of autophagy.
The results of Morris water maze test show that after the drug is continuously administered for 42d, the latency of the model group is prolonged, the frequency of passing through a platform is reduced, the frequency of effective areas is reduced, and the learning and memory abilities of the mouse are reduced. And the administration of ellagic acid group shortens the learning and memory ability comparison latency period of Morris water maze test, increases the frequency of passing through the platform and the frequency of the effective area, and the result is superior to the positive control medicament MF (P < 0.05). Therefore, the experiment method can further experiment and verify that the ellagic acid can obviously improve the learning and memory abilities of the aging model mouse, and has no statistically significant difference (P >0.05) with chloroquine. And the depilatory area of the administration groups EA, CQ and MF is obviously reduced through the appearance index, the result has statistical difference (P <0.001), and no obvious statistical difference (P >0.05) exists between the administration groups.
In the embodiment, a self-inhibitor chloroquine is adopted for carrying out an experiment, and the experimental result shows that the chloroquine has an anti-aging effect, can improve the learning and memory abilities of aging mice, and particularly has a very obvious effect on improving hair loss. And the hypoglycemic agent metformin also has a certain anti-aging effect and has a very obvious effect on improving hair loss.
The present invention and the embodiments thereof have been described above, but the description is not limited thereto, and the embodiments shown in the above embodiments are only one of the embodiments of the present invention, and the actual configuration is not limited thereto. In summary, those skilled in the art should appreciate that they can readily use the disclosed conception and specific embodiments as a basis for designing or modifying other structures for carrying out the same purposes of the present invention without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (9)
1. An experimental method for the influence of ellagic acid combined with an autophagy inhibitor on aging of a mouse model is characterized by comprising the following experimental steps:
s1: randomly selecting a plurality of mice, and randomly dividing the mice into 6 groups, namely a blank control group, an aging group, a positive control group, an Ellagic Acid (EA) group, an autophagy inhibitor group and a combined medicine group;
s2: adopting a D-galactose induced subacute aging method, injecting a 5% D-galactose solution into the mice of the blank control group subcutaneously on the neck and the back every day, continuously injecting for 42 days, constructing an aging animal model, simultaneously, administering the mice of the positive control group, the Ellagic Acid (EA) group, the autophagy inhibitor group and the combined drug group, performing intragastric lavage on the blank control group, and injecting physiological saline into the neck subcutaneously;
during the injection and administration period, the body weight of the mouse is measured and recorded every week, the water intake and the food intake of the mouse are measured and recorded every week, statistical treatment is carried out through statistical software, and differences of all groups are observed;
during the injection and administration, the depilation status of the mice was recorded weekly and the mice were photographed and recorded periodically, and then the size of the depilation area of the mice after each group of 42d was calculated by the image analysis software and compared.
S3: after injection and administration are finished, performing continuous Morris water maze experiments on all mice from day 2, wherein the water maze experiments comprise a positioning navigation experiment and a space exploration experiment; the space exploration experiment is after the positioning voyage experiment.
2. The method of claim 1, wherein the Morris water maze test of step S3 is performed for 6 days, the first 5 days are performed continuously for localization experiments, and the 6 th day is performed for space exploration experiments.
3. The experimental method for testing the influence of the ellagic acid combined autophagy inhibitor on the aging of the mouse model according to claim 1 or 2, wherein the administration manner of the positive control group in the step S2 is to perform metformin intragastric lavage, the Ellagic Acid (EA) group is ellagic acid intragastric lavage, the autophagy inhibitor group is chloroquine intraperitoneal injection, and the combined drug group is ellagic acid intragastric lavage and chloroquine intraperitoneal injection.
4. The method for testing the effect of ellagic acid in combination with an autophagy inhibitor on aging in a mouse model according to claim 1, wherein in the Morris water maze test of step S3, all mice are moved into a room of a behavioural test 1 hour before each day of the test to adapt to the environment of the room; the Morris water maze experiment adopts a Morris water maze experiment instrument, the Morris water maze experiment instrument comprises a movable platform and a water pool, the bottom and the periphery of the wall of the water pool are dyed into white, and a certain amount of titanium dioxide is poured into clear water in the water pool in advance to conceal the platform; a camera connected with a computer is arranged right above the water pool to record the complete swimming track of the mouse in a certain time, and the total swimming distance, time, swimming speed, the time required for finding the platform and the like of the mouse are automatically calculated.
5. The method for testing the effect of ellagic acid in combination with an autophagy inhibitor on aging in a mouse model according to claim 4, wherein said localized voyage test is performed 1 time each day in the morning and afternoon, and the test is performed by: respectively putting the mouse into water from 1 fixed water entry point facing the pool wall, starting timing while putting the mouse into the water, observing and recording the time required by the mouse to find an underwater hidden platform, wherein the result is the escape latency; if the platform is not found successfully within 60s, the experimenter guides the mouse to a platform hidden under water, keeps standing for 15s on the platform to observe the surrounding environment, and records the latency as 60 s.
6. The method for testing the effect of ellagic acid in combination with an autophagy inhibitor on aging in a mouse model according to claim 4, wherein the experimental operation of the space exploration test is: the platform hidden in the water is removed, any position in the fixed water pool is used as a water entry point of the experiment, the mouse swims in the water pool to explore and search the platform for 60s, and the escape latency, the swimming speed, the total swimming time of the quadrant where the original platform is located and the times of crossing the position of the original platform during the experiment are recorded.
7. The method for testing the effect of ellagic acid in combination with an autophagy inhibitor on aging in a mouse model according to claim 1, wherein the image analysis software in step S2 is imageproplus.
8. The new application of the metformin is characterized in that the metformin is applied to preparing a medicament for preventing and improving hair loss.
9. The new application of the chloroquine is characterized in that the chloroquine is applied to the preparation of the medicine for preventing and improving the hair loss.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110085946.2A CN112791089B (en) | 2021-01-22 | 2021-01-22 | Experimental method for influence of ellagic acid combined with autophagy inhibitor on aging of mouse model |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110085946.2A CN112791089B (en) | 2021-01-22 | 2021-01-22 | Experimental method for influence of ellagic acid combined with autophagy inhibitor on aging of mouse model |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112791089A true CN112791089A (en) | 2021-05-14 |
| CN112791089B CN112791089B (en) | 2023-10-27 |
Family
ID=75811145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110085946.2A Active CN112791089B (en) | 2021-01-22 | 2021-01-22 | Experimental method for influence of ellagic acid combined with autophagy inhibitor on aging of mouse model |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112791089B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090123564A1 (en) * | 2006-03-31 | 2009-05-14 | Rajesh Jain | Novel compositions for hair disorders and process of preparation thereof |
| WO2015084721A1 (en) * | 2013-12-02 | 2015-06-11 | Tabaczynski David A | Inhibition of isoprenoid biosynthetic pathways to treat autoimmune disorders |
| CN107247095A (en) * | 2017-05-25 | 2017-10-13 | 武汉大学 | A kind of construction method of the rat model for oxidation-resisting and caducity drug screening based on metabonomic analysis |
| WO2019204183A1 (en) * | 2018-04-16 | 2019-10-24 | The Regents Of The University Of California | Methods and compositions for hair growth by activating autophagy |
-
2021
- 2021-01-22 CN CN202110085946.2A patent/CN112791089B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090123564A1 (en) * | 2006-03-31 | 2009-05-14 | Rajesh Jain | Novel compositions for hair disorders and process of preparation thereof |
| WO2015084721A1 (en) * | 2013-12-02 | 2015-06-11 | Tabaczynski David A | Inhibition of isoprenoid biosynthetic pathways to treat autoimmune disorders |
| CN107247095A (en) * | 2017-05-25 | 2017-10-13 | 武汉大学 | A kind of construction method of the rat model for oxidation-resisting and caducity drug screening based on metabonomic analysis |
| WO2019204183A1 (en) * | 2018-04-16 | 2019-10-24 | The Regents Of The University Of California | Methods and compositions for hair growth by activating autophagy |
| CN112004554A (en) * | 2018-04-16 | 2020-11-27 | 加州大学董事会 | Methods and compositions for hair growth by activating autophagy |
| US20210145833A1 (en) * | 2018-04-16 | 2021-05-20 | The Regents Of The University Of California | Methods and Compositions for Hair Growth by Activating Autophagy |
Non-Patent Citations (1)
| Title |
|---|
| 王玲: "癌基因H-Ras过度表达抑制人成纤维细胞自噬", pages 072 - 20 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112791089B (en) | 2023-10-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102786414B (en) | Compound for treating and/or preventing neurodegenerative related disease | |
| CN103505731A (en) | Applications of 1 type cysteinyl leukotriene receptor antagonist on preparation of medicament for treating the Alzheimer disease | |
| CN108864311A (en) | A kind of inhibition MD2 and the protein bound small peptide of CIRP and its application | |
| CN102151258A (en) | Application of Alpha-mangostin in preparing medicines for treating Alzheimer's disease | |
| CN109276711B (en) | Application of manganese type high-stability superoxide dismutase in improving autism and product | |
| CN103156876B (en) | Medicine composition for treating central nervous system diseases and preparation method and application thereof | |
| WO2020052629A1 (en) | Application of p300 activator ctpb and derivative thereof in improving collagen col17a1 expression | |
| CN112791089B (en) | Experimental method for influence of ellagic acid combined with autophagy inhibitor on aging of mouse model | |
| RU2405572C1 (en) | Method of face and neck skin rejuvenation in women | |
| CN102247347B (en) | Application of taurine in preparing medicament for preventing nerve cell damage caused by dependence producing medicaments | |
| CN102283858B (en) | Application of lycium barbarum polysaccharides for preparing drugs for preventing and treating chronic stress and posttraumatic stress disorder | |
| CN101120946A (en) | Medicine for treating alzheimer's disease | |
| CN111773204B (en) | Application of sodium dichloroacetate in preparing medicine for treating vascular dementia | |
| CN108079011A (en) | Application of the Ali red polysaccharide in prevention or/and treatment Alzheimer disease drug is prepared | |
| CN113476454B (en) | Application of ICG-001 in preparation of medicine for treating autism | |
| CN104083345A (en) | Application of lycopene in preparation of medicine for prevention and treatment senile dementia | |
| CN113350488B (en) | Application of oral hypoglycemic peptide OHP in preparation of medicine for resisting neurodegenerative diseases | |
| CN109289002B (en) | Medicinal and edible composition | |
| CN116407546A (en) | Application of N-acetylmannosamine in preparation of medicines | |
| CN109674774B (en) | Application of propane-1-alcohol compound in preparation of medicine for treating cerebral hemorrhage | |
| WO2022222948A1 (en) | Pharmaceutical composition containing jak3/jak1/tbk1 selective inhibitor and medical use thereof | |
| CN114209680A (en) | Application of astaxanthin in preparation of medicine for treating vascular dementia | |
| CN104473915A (en) | Application of sivelestat as medicine for treating epilepsy | |
| CN105796571A (en) | Application of lupenone to preparation of drug for prevention and/or treatment of senile dementia and preparation | |
| CN116370606A (en) | Application of schistosome-derived peptide in preparation of medicament for treating depression |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |