CN104546829A - Application of xyloccensin K and analogues thereof in preparation of antidepressant medicines or foods - Google Patents
Application of xyloccensin K and analogues thereof in preparation of antidepressant medicines or foods Download PDFInfo
- Publication number
- CN104546829A CN104546829A CN201410739756.8A CN201410739756A CN104546829A CN 104546829 A CN104546829 A CN 104546829A CN 201410739756 A CN201410739756 A CN 201410739756A CN 104546829 A CN104546829 A CN 104546829A
- Authority
- CN
- China
- Prior art keywords
- different
- xylocarpus granatum
- mice
- xyloccensin
- xylocarpus
- 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
- 239000000935 antidepressant agent Substances 0.000 title claims abstract description 22
- 235000013305 food Nutrition 0.000 title claims abstract description 17
- 239000003814 drug Substances 0.000 title abstract description 20
- 230000001430 anti-depressive effect Effects 0.000 title abstract description 15
- 229940005513 antidepressants Drugs 0.000 title abstract description 13
- GZYBZGFGYJNASN-UHFFFAOYSA-N xyloccensin K Natural products COC(=O)CC1C(C)(C)C2OC3C2C(=O)C1(C)C4CCC5(C)C(OC(=O)CC5(O)C34)c6cocc6 GZYBZGFGYJNASN-UHFFFAOYSA-N 0.000 title abstract description 8
- OQQDWKJSAQRSAX-GXXYURFWSA-N xyloccensin k Chemical compound C=1([C@H]2[C@]3(C)CC[C@@H]4[C@@]5(C)C(=O)[C@H]6C[C@]4([C@@]3(CC(=O)O2)O)O[C@H]6C(C)(C)[C@H]5CC(=O)OC)C=COC=1 OQQDWKJSAQRSAX-GXXYURFWSA-N 0.000 title abstract description 8
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 229940079593 drug Drugs 0.000 title abstract description 6
- 240000005069 Xylocarpus granatum Species 0.000 claims description 74
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 21
- 238000002474 experimental method Methods 0.000 abstract description 17
- 229960004688 venlafaxine Drugs 0.000 abstract description 13
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 abstract description 13
- 230000036541 health Effects 0.000 abstract description 6
- 208000019901 Anxiety disease Diseases 0.000 abstract description 3
- 230000036506 anxiety Effects 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 43
- 238000012360 testing method Methods 0.000 description 18
- 239000000725 suspension Substances 0.000 description 14
- 239000013641 positive control Substances 0.000 description 11
- 239000000284 extract Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 8
- 230000002496 gastric effect Effects 0.000 description 8
- 238000001802 infusion Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000001768 carboxy methyl cellulose Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 7
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000007667 floating Methods 0.000 description 6
- 238000007689 inspection Methods 0.000 description 6
- 230000008925 spontaneous activity Effects 0.000 description 6
- 230000006399 behavior Effects 0.000 description 5
- 230000009182 swimming Effects 0.000 description 5
- 241000581650 Ivesia Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 4
- 239000003651 drinking water Substances 0.000 description 4
- 235000020188 drinking water Nutrition 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 150000002630 limonoids Chemical class 0.000 description 3
- -1 sesquiterpenoids Natural products 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 241000985616 Xylocarpus Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229940109262 curcumin Drugs 0.000 description 2
- 235000012754 curcumin Nutrition 0.000 description 2
- 239000004148 curcumin Substances 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000012048 forced swim test Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 150000003648 triterpenes Chemical class 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- 208000007415 Anhedonia Diseases 0.000 description 1
- 244000018217 Artocarpus elasticus Species 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000007027 Oral Candidiasis Diseases 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 241000287411 Turdidae Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000006400 anxiety behaviour Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- MGRRGKWPEVFJSH-UHFFFAOYSA-N dianthrone Natural products C12=CC=CC=C2C(=O)C2=CC=CC=C2C1=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MGRRGKWPEVFJSH-UHFFFAOYSA-N 0.000 description 1
- 239000002037 dichloromethane fraction Substances 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 229930004069 diterpene Natural products 0.000 description 1
- 125000000567 diterpene group Chemical group 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 210000002500 microbody Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000000407 monoamine reuptake Effects 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000002444 phloroglucinyl group Chemical class [H]OC1=C([H])C(O[H])=C(*)C(O[H])=C1[H] 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 229940126731 protein tyrosine phosphatase inhibitor Drugs 0.000 description 1
- 239000003806 protein tyrosine phosphatase inhibitor Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000002438 stress hormone Substances 0.000 description 1
- 230000004938 stress stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000003568 synaptosome Anatomy 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/33—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
- 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)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to new application of xyloccensin K and analogues thereof and particularly relates to application of xyloccensin K and analogues thereof in preparation of antidepressant medicines. The xyloccensin K provided by the invention can be used for preparing antidepressant medicines, health products or foods. Experiments show that xyloccensin K and analogues thereof have definite effects on treating depression, have a certain effect on inhibiting anxiety and are basically equivalent to venlafaxine which is a common antidepressant medicine in effect. In addition, as a component extracted from a natural product, the xyloccensin K has little side effects on the human body and is suitable for long-term use.
Description
Technical field
The present invention relates to the novelty teabag of a kind of different xylocarpus granatum element K and analog thereof, be specifically related to it and preparing the purposes in anti-depression drug or food.
Background technology
Xylocarpus granatum (Xylocarpus granatum Koenig.) is Meliaceae Xylocarpus Koenig plant, uses traditionally as astringent, antipyretic, and can be used for the diseases such as treatment malaria, thrush, cholera, dysentery and diarrhoea.The limonoid (limonoids) be rich in xylocarpus granatum is that the large class that occurring in nature exists has the triterpenes secondary metabolite of complex three-dimensional topological structure; the biological activity of the wide spectrum that the changeable limonoid of complex structure of this compounds demonstrates, as antibacterial, AntiHIV1 RT activity, parasite killing, malaria, anti-botullnus, antiallergic, check melanin formation, antiinflammatory, antitumor and neuroprotective isoreactivity.Multinomial research has been carried out at present about the extract of xylocarpus granatum, be used for the treatment of diabetes and dyslipidemia as patent CN200680041586.X discloses Xylocarpus Koenig extract, wherein biologically-active moiety comprises different xylocarpus granatum element K(xyloccensin K) etc. various ingredients; Patent CN201210552780.1 discloses the activity that xylocarpus granatum element in heptan (xylogranatumin G) has obvious inhibition tumor cell; Patent CN201210564022.1 discloses xylocarpus granatum alkali A prime (granatumine A) as the application of protein tyrosine phosphatase inhibitor in treatment diabetes, obesity and complication thereof.Visible, there is no in prior art and xylocarpus granatum and/or xylocarpus granatum extract monomer component be used for the treatment of or the purposes of prevention of depression.
Depression is a kind of mental sickness seriously jeopardizing human physical and mental health, and main manifestations is anhedonia, hebetude, with other psychology in various degree such as anxiety, sleep disorder and (or) somatization.World Health Organization (WHO) (WHO) predicts the year two thousand twenty depression will become second largest disabling disease, and front Chinese depression prevalence reaches 3%-5%, patient Yue Da 2,600 ten thousand people.Symptoms of depression is changeable, pathogenesis is failed to understand so far.More consistent, stress be the important trigger that depression occurs, strong, lasting stress stimulation causes the imbalance of body Neuro-endocrine-immunity system, and typical change comprises maincenter related brain areas nerve accommodation and sexually revises and stress hormone horizontal abnormality.At present clinically the treatment of depression mainly based on Drug therapy, the existing medicine overwhelming majority exist onset delay, remission not thoroughly, the limitation such as the high and side effect of relapse rate is large.The newly-developed antidepressant of development of new, safety becomes the focus of current research.
Natural plant have safety, hypotoxicity, few side effects, efficient, have no drug resistance thus the feature such as reusable.The natural pharmaceutical resources of China enriches, and demand is extensive, has good development foundation.Large quantity research shows, natural plant extracts has antiinflammatory, antitumor, defying age isoreactivity, also shows good development and application prospect at anti-depression aspect.The antidepressant activity plant component found mainly contains the type compounds such as benzo dianthrone class, flavonoid, oligosaccharides, alkaloids, phloroglucinol derivatives, sesquiterpenoids, Diterpenes, triterpenes, saponin, organic acid.Flavone compound in Herba Hyperici Monogyni by improving maincenter Monoamine, suppress synaptosome to monoamine-reuptake play antidepressant effect show as obviously shorten forced swimming test (forced swimming test FST) and outstanding tail test (tail suspension test TST) test in the mice dead time, the preparation produced by its extract is widely used in treatment in all states of America and Europe clinically, mild depression.Rhizoma Zingiberis Recens extract curcumin has been proved certain antidepressant effect, its effect may be relevant with furan system, further research finds, curcumin significantly can increase frontal cortex, Hippocampus and hypothalamic tuber on content of monoamine transmitters, and its antidepressant effect can be relevant by Erk-BDNF-CREB signal pathway.Other are as have also discovered antidepressant effective ingredient from the extract of Semen Arecae, Radix Morindae Officinalis etc.Natural drug antidepressant activity composition selection becomes key areas and the study hotspot of antidepressant drug research and development.
Summary of the invention
A kind of different xylocarpus granatum element K and analog thereof is the object of the present invention is to provide to prepare the purposes in anti-depression drug or food, different xylocarpus granatum element K has higher safety and human body adaptability as a kind of natural plant extracts, and because toxic and side effects is little, the medium-term and long-term use of food can be added into.
Technical scheme of the present invention is as follows:
Different xylocarpus granatum element K of the present invention is preparing the purposes in anti-depression drug or food, the structure of described different xylocarpus granatum element K as shown in structural formula (1),
Structural formula (1).
Different xylocarpus granatum element K analog of the present invention is preparing the purposes in anti-depression drug or food, and the structure of described xylocarpus granatum element K analog is as shown in structural formula (2);
Structural formula (2),
Wherein R
1and R
2be selected from hydrogen, carbonyl compound, C
1~ C
18substituted or non-substituted alkyl, C
1~ C
18substituted or non-substituted aryl.
Depression of the present invention comprises individual event depression clinically or two-way depression.
Medicine of the present invention comprises based on the medicine of therapeutic purposes and the health product based on prevention object.
The present invention protects different xylocarpus granatum element K(xyloccensin K) purposes in the medicine preparing Cure of depression or food; as long as therefore add the different xylocarpus granatum element compositions of K or product based on antidepressant object all belong to the scope that the present invention protects, and be not particularly limited in this product and only have different xylocarpus granatum element K component.And as known in the field, other effective ingredient or adjuvant can be added when being prepared as medicine or food, forming final products.The adjuvant that can add comprises excipient, pharmaceutical carrier, disintegrating agent, filler etc.
The present invention protects the purposes of derivant in the medicine preparing Cure of depression or food of different xylocarpus granatum element K, and described derivant is with structural formula (2) for parent nucleus, R
1and R
2be selected from the substituted or non-substituted alkyl of hydrogen, carbonyl compound, C1 ~ C18, compound that substituted or non-substituted aryl obtains.
The invention provides the novelty teabag of a kind of different xylocarpus granatum element K, it can be applicable to prepare the medicine of depression, health product or food.When being prepared as medicine, the effective dose of different xylocarpus granatum element K is oral 0.5-5mg/kg, (or injection 0.1-2mg/Kg); When being prepared as health product, the effective dose of different xylocarpus granatum element K is oral 0.1-1mg/kg; When being prepared as food, the different xylocarpus granatum element K adding 0.1-1mg/kg can be selected in beverage or food.
Beneficial effect of the present invention is:
The invention provides the novelty teabag of a kind of different xylocarpus granatum element K, it can be applicable to prepare the medicine of depression, health product or food.Experiment proves, different xylocarpus granatum element K and analog thereof have definite curative effect to depression, and have certain angst resistance effect, basic suitable with the effect of antidepressant common medicine venlafaxine; Meanwhile, because it is natural product extraction composition, little to the side effect of human body, can life-time service.
Accompanying drawing explanation
Fig. 1 is embodiment 1 different xylocarpus granatum element K's
1h-NMR spectrogram;
Fig. 2 is embodiment 1 different xylocarpus granatum element K's
13c NMR spectrogram;
Fig. 3 be embodiment 1 different xylocarpus granatum element K with HMBC spectrogram;
Fig. 4 is the NOESY spectrogram of embodiment 1 different xylocarpus granatum element K;
Fig. 5 is the flow chart of embodiment test method;
Fig. 6 is the experimental result of the mouse forced swimming test of embodiment 2;
Fig. 7 is the experimental result of the Tail suspension test of embodiment 3;
Fig. 8 is the experimental result of the mice spacious field experiment of embodiment 4;
Fig. 9 is the experimental result of the spontaneous activity in mice experiment of embodiment 5.
Detailed description of the invention
The preparation of embodiment 1 different xylocarpus granatum element K
Different xylocarpus granatum element K is separation and Extraction monomer out from xylocarpus granatum, reaches more than 98% through Purity.
The extraction separation and purification method of different xylocarpus granatum element K
Get xylocarpus granatum medical material (fruits and seeds) about 20 Kg after pulverizing, extract with 95% ethanol merceration, each soak time is one week, extracts 3 times.Extracting liquid filtering, is evaporated to paste, obtains extractum.Extractum is suspended in water, uses petroleum ether, dichloromethane and extraction into ethyl acetate respectively, extract concentrating under reduced pressure, obtain petroleum ether part extractum, dichloromethane fractions extractum and ethyl acetate portion extractum.Adopt silica gel column chromatography, polydextran gel, Preparative TLC method to be separated with the chemical composition of preparative high performance liquid chromatography to above position, the different xylocarpus granatum element K monomeric compound obtained is white powdery solids.ESI-MS
m/z: 487 [M+H]
+, molecular formula is C
27h
34o
8.Contrast with the common thin layer chromatography of different xylocarpus granatum element K reference substance, use petroleum ether-acetone respectively, when petroleum ether-ethyl acetate and methylene chloride-methanol develop the color as developing solvent system, said extracted thing contrasts with the common thin layer chromatography of different xylocarpus granatum element K reference substance,
r f value and the behavior of colour developing are all consistent, and after mixing, fusing point does not decline, and determine that extract is different xylocarpus granatum element K.
1h-NMR spectrogram is shown in accompanying drawing 1,
13c NMR spectrogram is shown in that accompanying drawing 2, HMBC spectrogram is shown in that accompanying drawing 3, NOESY spectrogram is shown in accompanying drawing 4.
Embodiment 2 mouse forced swimming test model
Laboratory animal adopts male mice in kunming, and mice freely ingests drinking-water, body weight about 30 grams during experiment.
Quantitative different xylocarpus granatum element K is placed in mortar, adds 0.5% quantitative carboxymethylcellulose sodium solution grinding and make into suspension, make different xylocarpus granatum element K-0.5% sodium carboxymethyl cellulose suspension; Positive control medicine is venlafaxine.Administering mode is gastric infusion.
Mice is divided into 5 groups at random, be divided into dosage group (XM group 15mg/kg), different xylocarpus granatum element K high dose group (XH group 50 mg/kg), venlafaxine positive controls (VEN group 10 mg/kg) in negative control group (solvent group), different xylocarpus granatum element K low dose group (XL group 5mg/kg), different xylocarpus granatum element K, often organize 12.
As shown in Figure 5, mice starts administration after the adaptability raising of 5 days, and first time administration counted administration first day, successive administration 7 days the same day, and after last administration, half an hour carries out Behavior test.
Behavioristics's detection method: swimming device is made (high 24 ㎝ of glass jar, diameter 15 ㎝, the depth of water 17 ㎝, water temperature 24 ± 2 DEG C) by transparent organic glass and is placed in one by mice, adapts to after 2 minutes, records the mice floating dead time in latter 4 minutes.The floating dead time is defined as the micro-body of curling up of mice, time in floating state.
Experimental result represents with mean+/-standard error, with the process of t inspection statistics.
Forced swim test is classical antidepressants screening model, the floating dead time that effective antidepressants can make mice swim, as shown in the experimental result of Fig. 6, different xylocarpus granatum element K has significant antidepressant effect, compared with Vehicle controls group, 15,50mg/kg 7 days continuous gastric infusions significantly can reduce the floating dead time (p<0.05 of mice, p<0.01), compared with positive controls two groups of different xylocarpus granatum element K administration groups all without significant difference.
Illustrate that different xylocarpus granatum element K significantly can reduce the mice floating dead time, its action effect is suitable with venlafaxine.
Embodiment 3 Tail suspension test
Laboratory animal adopts male mice in kunming, and mice freely ingests drinking-water, body weight about 30 grams during experiment.
Using 0.5% sodium carboxymethyl cellulose as solvent, the fresh different xylocarpus granatum element K-0.5% sodium carboxymethyl cellulose suspension of preparation before experiment; Positive control medicine is venlafaxine.Administering mode is gastric infusion.
Mice is divided into 5 groups at random, be divided into dosage group (XM group 15mg/kg), different xylocarpus granatum element K high dose group (XH group 50 mg/kg), venlafaxine positive controls (VEN group 10mg/kg) in negative control group (solvent group), different xylocarpus granatum element K low dose group (XL group 5mg/kg), different xylocarpus granatum element K, often organize 12.As shown in Figure 5, mice starts administration after the adaptability raising of 5 days, and first time administration counted administration first day, successive administration 7 days the same day, and after last gastric infusion, half an hour carries out Behavior test.
Experimental result represents with mean+/-standard error, with the process of t inspection statistics.
According to European Journal of Pharmacology, 2001, the experimental technique recorded in 415:197 builds Tail suspension test model, mice was hung upside down cross bar upper 6 minute apart from ground 60cm, the fixing site of mice is apart from tail slightly 1cm place, adapts to after 2 minutes, observes latter 4 minutes mice dead times, motionless state is defined as mice and stops struggling, and body is relaxation state.
Experimental result represents with mean+/-standard error, with the process of t inspection statistics.
Tail suspension test is classical screening antidepressants experimental model, presents desperate state after mouse tail suspension a period of time, stops struggling.Effective antidepressant drug can make the dead time in mouse tail suspension process shorten.This experiment shows; different xylocarpus granatum element K has significant antidepressant effect; as shown in the experimental result of Fig. 7, compared with Vehicle controls group, 5,15,50mg/kg different xylocarpus granatum element K administration all significantly can reduce the mouse tail suspension dead time (5 mg/kg p<0.05; 15,50 mg/kg P<0.01); Compared with positive controls, three groups of different xylocarpus granatum element K administration group differences do not have significance.
Illustrate that xylocarpus granatum element K can significantly reduce the mouse tail suspension dead time, its action effect is suitable with venlafaxine.
The spacious field experiment of embodiment 4 mice
Laboratory animal adopts male mice in kunming, and mice freely ingests drinking-water, body weight about 30 grams during experiment.
Using 0.5% sodium carboxymethyl cellulose as solvent, the fresh different xylocarpus granatum element K-0.5% sodium carboxymethyl cellulose suspension of preparation before experiment; Positive control medicine is venlafaxine.Administering mode is gastric infusion.
Mice is divided into 5 groups at random, be divided into dosage group (XM group 15mg/kg), different xylocarpus granatum element K high dose group (XH group 50 mg/kg), venlafaxine positive controls (VEN group 10 mg/kg) in negative control group (solvent group), different xylocarpus granatum element K low dose group (XL group 5mg/kg), different xylocarpus granatum element K, often organize 12.As shown in Figure 5, mice starts administration after the adaptability raising of 5 days, and first time administration counted administration first day, successive administration 7 days the same day, and after last gastric infusion, half an hour carries out Behavior test.
Mice is put in spacious field, observes 10 minutes, record mice in latter 6 minutes and stop the cumulative time in spacious center court region.Experimental result represents with mean+/-standard error, with the process of t inspection statistics.
Mice spacious field experiment is the experimental model of classical evaluation anxiolytic effect, and mice is placed in a period of time behind spacious field, and it exposes selection preference at exploration middle section and space and embodies its anxiety behavior.Effective anxiolytic drugs can make mice middle section time of staying in the test of spacious field increase.This experiment shows, different xylocarpus granatum element K has significant anxiolytic effect, as shown in the experimental result of Fig. 8, compared with Vehicle controls group, 50mg/kg different xylocarpus granatum element K administration significantly can increase mice the spacious center court region time of staying (p<0.05); Compared with positive controls, different xylocarpus granatum element K high dose administration group difference does not have significance.
Illustrate that different xylocarpus granatum element K significantly can increase the middle section time of staying in the testing experiment of mice spacious field, when dosage reaches 50 mg/kg, action effect is suitable with venlafaxine.
Embodiment 5 spontaneous activity in mice
Laboratory animal adopts male mice in kunming, and mice freely ingests drinking-water, body weight about 30 grams during experiment.
Using 0.5% sodium carboxymethyl cellulose as solvent, the fresh different xylocarpus granatum element K-0.5% sodium carboxymethyl cellulose suspension of preparation before experiment; Positive control medicine is venlafaxine.Administering mode is gastric infusion.
Mice is divided into 5 groups at random, be divided into dosage group (15mg/kg), different xylocarpus granatum element K high dose group (50 mg/kg), venlafaxine positive controls (10 mg/kg) in negative control group (solvent group), different xylocarpus granatum element K low dose group (5mg/kg), different xylocarpus granatum element K, often organize 12.As shown in Figure 5, mice starts administration after the adaptability raising of 5 days, and first time administration counted administration first day, successive administration 7 days the same day, and after last gastric infusion, half an hour carries out Behavior test.
Experimental result represents with mean+/-standard error, with the process of t inspection statistics.
Mice is put in spontaneous activity case, observe 10 minutes, record spontaneous activity in mice situation in latter 6 minutes, experimental result represents with mean+/-standard error, with the process of t inspection statistics.
As shown in the experimental result of Fig. 9, compared with matched group, different xylocarpus granatum element K administration group spontaneous activity in mice does not have significant change.Illustrate that the spontaneous activity of xylocarpus granatum element K to mice has no significant effect, in test dose, remarkable effect be there is no to the neural activity of mice, not there is neurotoxicity.
Claims (2)
1. different xylocarpus granatum element K is preparing the purposes in anti-depression drug or food, the structure of described different xylocarpus granatum element K as shown in structural formula (1),
Structural formula (1).
2. different xylocarpus granatum element K analog is preparing the purposes in anti-depression drug or food, and the structure of described xylocarpus granatum element K analog is as shown in structural formula (2);
Structural formula (2),
Wherein R
1and R
2be selected from hydrogen, carbonyl compound, C
1~ C
18substituted or non-substituted alkyl, C
1~ C
18substituted or non-substituted aryl.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410739756.8A CN104546829B (en) | 2014-12-08 | 2014-12-08 | Purposes of the different xylocarpus granatum element K and the like in anti-depression drug or food is prepared |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410739756.8A CN104546829B (en) | 2014-12-08 | 2014-12-08 | Purposes of the different xylocarpus granatum element K and the like in anti-depression drug or food is prepared |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104546829A true CN104546829A (en) | 2015-04-29 |
CN104546829B CN104546829B (en) | 2018-01-12 |
Family
ID=53064612
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410739756.8A Active CN104546829B (en) | 2014-12-08 | 2014-12-08 | Purposes of the different xylocarpus granatum element K and the like in anti-depression drug or food is prepared |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN104546829B (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1513853A (en) * | 2003-08-07 | 2004-07-21 | 中国科学院南海海洋研究所 | Limonin compound-wood fruit chinaberry lactone and its use |
WO2007031830A2 (en) * | 2005-09-12 | 2007-03-22 | Council Of Scientific And Industrial Research | An extract from xylocarpus useful for the treatment of diabetes and dyslipidemia |
CN101781355A (en) * | 2010-01-22 | 2010-07-21 | 张登科 | Method for preparing limonin, composition and application thereof |
-
2014
- 2014-12-08 CN CN201410739756.8A patent/CN104546829B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1513853A (en) * | 2003-08-07 | 2004-07-21 | 中国科学院南海海洋研究所 | Limonin compound-wood fruit chinaberry lactone and its use |
WO2007031830A2 (en) * | 2005-09-12 | 2007-03-22 | Council Of Scientific And Industrial Research | An extract from xylocarpus useful for the treatment of diabetes and dyslipidemia |
CN101330921A (en) * | 2005-09-12 | 2008-12-24 | 科学与工业研究会 | An extract from xylocarpus useful for the treatment of diabetes and dyslipidemia |
CN101781355A (en) * | 2010-01-22 | 2010-07-21 | 张登科 | Method for preparing limonin, composition and application thereof |
Non-Patent Citations (1)
Title |
---|
尹希,等: "木果楝素H抗抑郁活性的实验研究", 《中国科技论文在线》 * |
Also Published As
Publication number | Publication date |
---|---|
CN104546829B (en) | 2018-01-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103432184A (en) | Application of great burdock fruit extract in drug production or foods | |
CN101926865B (en) | Spina date seed depression-resolving and nerve-soothing composition and preparation method thereof | |
CN102641324B (en) | Herba gueldenstaedtia extract and uses thereof | |
CN102617698B (en) | Method for preparing fine dioscin and application of fine dioscin | |
CN102153614B (en) | Method for preparing effective monomer of total alkaloid extract of holarrhena antidysenterica and application thereof | |
CN103735653B (en) | A kind of Chinese medicine extract with anti-tumor activity and its production and use | |
CN103191198A (en) | Rhizoma corydalis extract as well as preparation method and use thereof | |
CN103463257A (en) | Fructus aurantii immaturus or fructus aurantii extract, its preparation method and application | |
CN105106816A (en) | Traditional Chinese medicine healthcare preparation with protection effect on chemical liver injury and preparing method thereof | |
CN102125573A (en) | Use of ginsenoside Rg1 in preparation of antidepressant | |
CN102898322B (en) | Compound and preparation method and application thereof | |
CN102178721A (en) | Application of fiveleaf gynostemma herb suspension and extract to preparation of drug for treating and resisting depression | |
CN101590212A (en) | Treatment mental sickness Chinese medicine composition and preparation method thereof, purposes and quality control | |
CN104586837B (en) | Purposes of the gray wool Cipadessa baecifera Miq A and the like in anti-depression drug is prepared | |
CN104288142B (en) | The xylocarpus granatum element H and the like purposes in preparing anti-depression drug or food | |
CN104546829A (en) | Application of xyloccensin K and analogues thereof in preparation of antidepressant medicines or foods | |
CN103880913B (en) | A kind of compound and application thereof with hepatoprotective effect | |
CN103142935A (en) | Traditional Chinese medicinal composition for treating lung cancer and liver cancer | |
CN106491719A (en) | A kind of extracting method of leaf of Broussonetia papyrifera (L.) L.Her.ex Vent. total phenolic acid extract and its application | |
CN101301357A (en) | Use of schisandra chinensis extract in anti-depression medicament | |
CN1970001B (en) | Pharmaceutical composition comprising kurarinone, magnolia vine fruit and ginseng for treating hepatitis | |
CN104189346A (en) | New pharmaceutical composition capable of promoting gastrointestinal motility and preparation method thereof | |
CN104739949A (en) | Composition for treating Parkinson disease and preparation method of composition | |
CN102648937A (en) | Application of polygala alkaline hydrolysis product composition in preparation of anti-senile dementia medicine | |
CN103142597B (en) | Ipecacuanha effective component composition, its preparation method and application |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |