CN103816142A - Application of Tibetan medicine duhat fruit tannin monomer - Google Patents
Application of Tibetan medicine duhat fruit tannin monomer Download PDFInfo
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- CN103816142A CN103816142A CN201410094394.1A CN201410094394A CN103816142A CN 103816142 A CN103816142 A CN 103816142A CN 201410094394 A CN201410094394 A CN 201410094394A CN 103816142 A CN103816142 A CN 103816142A
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- tannin
- folding
- monoamine oxidase
- pentahydroxydibenzo
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- 235000018553 tannin Nutrition 0.000 title claims abstract description 28
- 229920001864 tannin Polymers 0.000 title claims abstract description 28
- 239000001648 tannin Substances 0.000 title claims abstract description 28
- 239000000178 monomer Substances 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 244000234162 Eugenia cumini Species 0.000 title description 2
- 235000012097 Eugenia cumini Nutrition 0.000 title 1
- 235000013399 edible fruits Nutrition 0.000 title 1
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims abstract description 28
- ZELMDXUEWHBWPN-UHFFFAOYSA-N 3,4,8,9,10-pentahydroxybenzo[c]chromen-6-one Chemical compound OC1=C(O)C(O)=C2C3=CC=C(O)C(O)=C3OC(=O)C2=C1 ZELMDXUEWHBWPN-UHFFFAOYSA-N 0.000 claims abstract description 22
- 235000004515 gallic acid Nutrition 0.000 claims abstract description 14
- 229940074391 gallic acid Drugs 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 5
- FBSFWRHWHYMIOG-UHFFFAOYSA-N methyl 3,4,5-trihydroxybenzoate Chemical compound COC(=O)C1=CC(O)=C(O)C(O)=C1 FBSFWRHWHYMIOG-UHFFFAOYSA-N 0.000 claims abstract 6
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 claims abstract 3
- IBKQQKPQRYUGBJ-UHFFFAOYSA-N methyl gallate Natural products CC(=O)C1=CC(O)=C(O)C(O)=C1 IBKQQKPQRYUGBJ-UHFFFAOYSA-N 0.000 claims abstract 3
- 239000002899 monoamine oxidase inhibitor Substances 0.000 claims abstract 3
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 208000020401 Depressive disease Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 3
- 102000010909 Monoamine Oxidase Human genes 0.000 description 26
- 108010062431 Monoamine oxidase Proteins 0.000 description 26
- 241000700159 Rattus Species 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 13
- LEXBBZCFWJNTGC-UHFFFAOYSA-N gallicin Natural products C1CC(=C)C(O)CCC(C)=CC2OC(=O)C(C)C21 LEXBBZCFWJNTGC-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 230000003542 behavioural effect Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 6
- 230000000994 depressogenic effect Effects 0.000 description 6
- 238000003304 gavage Methods 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- 229940087098 Oxidase inhibitor Drugs 0.000 description 5
- 229940126214 compound 3 Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 230000009182 swimming Effects 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 3
- NYMGNSNKLVNMIA-UHFFFAOYSA-N Iproniazid Chemical compound CC(C)NNC(=O)C1=CC=NC=C1 NYMGNSNKLVNMIA-UHFFFAOYSA-N 0.000 description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229940070023 iproniazide Drugs 0.000 description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 2
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N 4-aminoantipyrine Chemical compound CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- 210000001951 dura mater Anatomy 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229960002464 fluoxetine Drugs 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000002311 liver mitochondria Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
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- 238000000746 purification Methods 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- -1 reflux Substances 0.000 description 2
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- 230000035882 stress Effects 0.000 description 2
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- 238000005406 washing Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GIYXAJPCNFJEHY-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1) Chemical compound Cl.C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 GIYXAJPCNFJEHY-UHFFFAOYSA-N 0.000 description 1
- DZGWFCGJZKJUFP-UHFFFAOYSA-N Tyramine Natural products NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000000806 cranial fontanelle Anatomy 0.000 description 1
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- 210000003141 lower extremity Anatomy 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
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- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
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- 210000003523 substantia nigra Anatomy 0.000 description 1
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- 229960003732 tyramine Drugs 0.000 description 1
- DZGWFCGJZKJUFP-UHFFFAOYSA-O tyraminium Chemical compound [NH3+]CCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-O 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
藏药萨折鞣质单体的用途，其成分为没食子酸、没食子酸甲酯、3,4,8,9,10-pentahydroxydibenzo[b,d]pyran-6-one在制备单胺氧化酶抑制剂中的用途；其特征在于没食子酸、没食子酸甲酯、3,4,8,9,10-pentahydroxydibenzo[b,d]pyran-6-one在制备治疗抑郁症、帕金森病药物中的用途。The use of Tibetan medicine Sazhe tannin monomer, whose components are gallic acid, methyl gallate, 3,4,8,9,10-pentahydroxydibenzo[b,d]pyran-6-one in the preparation of monoamine oxidase inhibitors Uses; it is characterized in that gallic acid, methyl gallate, and 3,4,8,9,10-pentahydroxydibenzo[b,d]pyran-6-one are used in the preparation of medicines for treating depression and Parkinson's disease.
Description
Technical field
The present invention relates to the purposes of tannin monomer.
Background technology
Along with the fast development of global economy and constantly increasing the weight of of the problem of an aging population, modern people's life stress is increasing, and depression and Parkinsonian patient are more and more.Therefore the research of Cure of depression and parkinson disease medicine (oxidase inhibitor class medicine) has caused people's broad interest.
Sa folding is a kind of conventional Tibetan medicine, is mainly used in the treatment of nephropathy and three calamity diseases in China Tibetan area, and its Original plant is duhat
syzygium cumini (l.) Skeelsfruit.This vegetalitas, is liked warm and moist weather on the sunny side, and suitable natural disposition is strong, distributed more widely, originates in Yunnan, Fujian, Guangdong, Guangxi; Be born in low height above sea level sparse woods or wilderness (Yang Yongchang. Tibetan medicine will [M]. Xining: the Qinghai People's Press, 1991:413.).But up to the present, there is not yet Sa folding tannin monomer gallic acid, gallicin, 3,4,8,9,10-pentahydroxydibenzo[b, d] purposes of pyran-6-one in preparation oxidase inhibitor.
Summary of the invention
The object of this invention is to provide the purposes of Sa folding tannin monomer.
The present invention is the purposes of Sa folding tannin monomer component, and Sa folding tannin monomer component is gallic acid, gallicin, 3,4,8,9,10-pentahydroxydibenzo[b, d] pyran-6-one, chemical constitution is respectively:
Compound
1(gallic acid)
Compound
2(gallicin)
Compound
3(3,4,8,9,10-pentahydroxydibenzo[b, d] pyran-6-one)
The purposes of Sa folding tannin monomer component, for the preparation of oxidase inhibitor.
Sa folding tannin monomeric compound of the present invention
1-
3structural Identification as follows:
Compound
1: meet ferric chloride ethanol and be navy blue.White, needle-shaped crystals (chloroform-methanol).
1H-NMR(400MHz,CD
3OD)
δ H:7.13(2H,s,H-2,6)。
13C-NMR(100MHz，CD
3OD)
δ C:158.6(C-7),146.8(C-3,5),139.2(C-4),122.3(C-1),110.7(C-2,6)。Above spectroscopic data and document (paint refined China, Guo Jianwei, Wu great Gang, etc. research and development of natural products, 2004,16 (3): 210-212.) spectral data of gallic acid of report is consistent, so this compound identification is gallic acid.
Compound
2: meet ferric chloride ethanol and be navy blue.Colourless crystalline particulate (methanol),
1h-NMR(CD
3oD, 400MHz)
δ h: 7.03 (2H, s, H-2,6), 3.80 (3H, s, OCH3).
13C-NMR（CD3OD，100MHz）
δ C：169.0(C-7)，146.5(C-3，5)，139.7(C-4)，121.4(C-1)，110.1(C-2，6)，52.2(C-8)。Above data and document (Shi Xiaofeng, Bai Chaohui, Liu Dongyan, etc. Chinese crude drug, 2012,35 (3): 404-406.) report gallicin spectral data consistent, therefore be accredited as gallicin.
Compound
3: meet ferric chloride ethanol and be navy blue.Yellow green powder,
1h-NMR(CD
3oD, 400MHz)
δ h: 8.44 (1H, d,
j=9.2 Hz, H-1), 7.37 (1H, s, H-7), 6.76 (1H, d,
j=9.2Hz, H-2).
13C-NMR（CD
3OD，100MHz）
δ C ：163.9(C-6)，146.8(?C-3)，146.5(C-8)，144.1(?C-10)，142.4(C-9)，141.0(C-4a)，133.3(C-4)，119.1(C-1)，118.5(C-10a)，112.9(C-10b)，112.4(?C-2)，111.7(C-6a)，108.1(C-7)。Above data and document (Bai N, He K, Roller M,
et al.
j Agric Food Chem, 2008,56 (24): 11668-11674.) report 3,4,8,9,10-Pentahydroxydibenzo [b, d] pyran-6-one spectral data is consistent, therefore be accredited as 3,4,8,9,10-Pentahydroxydibenzo [b, d] pyran-6-one.
The present invention adopts enzyme linked immunosorbent assay to study Sa folding tannin monomer: gallic acid, gallicin, 3,4,8,9,10-pentahydroxydibenzo[b, d] the pyran-6-one inhibition activity to monoamine oxidase, MAO in vitro, result shows, they all have good monoamine oxidase inhibitory activity.In order further to confirm antidepressant and the anti-Parkinson effect of Sa folding tannin monomer component, the present invention studied Sa folding tannin monomer component on the depressed mice of behavioral despair stress behavioral competence impact (Zhang Juntian. modern pharmacology experimental technique (first volume) [M]. Beijing Medical University, combined publication society of China Concord Medical Science University, 1998.1061) with on 6-OHDA(6-hydroxy dopamine) due to parkinson rat behavioral competence impact (Wu Lingbo etc. modern combination of Chinese and Western medicine will, 2009,18
(3)：251-252）。Result shows, Sa folding tannin monomer component gallic acid, gallicin, 3,4,8,9,10-pentahydroxydibenzo[b, d] pyran-6-one all can obviously improve the behavioral competence of depressed mice and parkinson rat.Above results suggest, Sa folding tannin monomer component gallic acid, gallicin, 3,4,8,9,10-pentahydroxydibenzo[b, d] pyran-6-one can be for the preparation of prevention, Cure of depression and Parkinsonian medicine.
The specific embodiment
The present invention is the purposes of Sa folding tannin monomer, and Sa folding tannin monomer component is gallic acid, gallicin, 3,4,8,9,10-pentahydroxydibenzo[b, d] pyran-6-one, its chemical constitution is respectively:
Compound
1(gallic acid)
Compound
2(gallicin)
Compound
3(3,4,8,9,10-pentahydroxydibenzo[b, d] pyran-6-one)
The purposes of Sa folding tannin monomer, its medical usage is preparation oxidase inhibitor.Oxidase inhibitor refers to for depression, or the medicine of Parkinson's disease.The purposes of above-described Sa folding tannin monomer, with acceptable carrier pharmaceutically, or other excipient combines, and make the interior of oral administration administration according to conventional method and use type dosage form, or the injection of parenteral administration, or other dosage form.
Below in conjunction with instantiation, the present invention is further described, but do not limit the present invention.
Embodiment 1 Sa folding tannin monomer component gallic acid, gallicin, 3,4,8,9,10-pentahydroxydibenzo[b, d] preparation of pyran-6-one
Dry Sa folding (5kg) is pulverized, and the industrial alcohol with 95% extracts, reflux, extract, 2 times, and each 2h, sucking filtration, is evaporated to extractum, reclaims ethanol, then extractum is suspended in 5L distilled water, with 4 mol/L NaOH
Adjust aqueous suspension to pH=10～11, hold over night; Sucking filtration; Adjust pH=2～3 with 2 mol/L HCl solution again, with the extraction of ethyl acetate equal-volume, concentrating under reduced pressure, reclaims ethyl acetate, obtains the total organic acids of Sa folding.Sa is rolled over to total organic acids and carry out polyamide (100-200 order) column chromatography, successively with water, 30%, 50%, 70%, 90% methanol gradient elution, discard water elution part, 30%～90% eluting part, TLC follows the tracks of merging, obtains 6 parts (Fr.1～6).Measure the monoamine oxidase inhibitory activity of Fr.1～6, find that component Fr.1 and Fr.3 have remarkable activity, its IC
50be respectively 0.3 mg/L, 11.3 mg/L.Fr.1 is through silica gel column chromatography, and chloroform-methanol (20: 1～1: 1) separates and obtains Fr.1a～1c; Fr.1c, through LH-20 column chromatography methanol-eluted fractions purification, obtains compound
1(120 mg).Fr. 3 through polyamide column chromatography, acetone-methanol (40: 1～1: 1) gradient elution obtains Fr.3a～3e, respectively Fr.3a and Fr.3c being carried out to HPLC separates, methanol-water (30: 70～80: 20), contain 0.1% trifluoroacetic acid) eluting, finally use LH-20 column chromatography, methanol-eluted fractions purification, obtains compound
2(10 mg), compound
3(150 mg).
Embodiment 2 enzyme linked immunosorbent assaies are measured the monoamine oxidase inhibitory activity of Sa folding tannin monomer component
Utilize enzyme linked immunosorbent assay to measure Sa folding tannin monomer component: compound
1-
3the suppression ratio of (concentration is 50 μ g/ml), the positive contrast medicine of iproniazid phosphate.Specific experiment process is as follows:
(1) preparation of monoamine oxidase, MAO:
De-1 female wistar rat cervical vertebra is put to death, take out its liver, liver is shredded, with phosphate buffer (pH=7.6) washing several, after washes clean, add 20ml, 0.3M sucrose buffer carries out homogenate, fully, after homogenate, respectively gets 10ml and pours in two 50ml centrifuge tubes.With 20ml, after 0.3M sucrose buffer washing homogenizer, respectively get 10ml and pour in foregoing centrifuge tube.After counter balance trim, at-4 ℃, the centrifugal 10min of 1000 × g.Draw supernatant, by supernatant trim, the centrifugal 15min of 1200 × g, draws supernatant, by supernatant trim, the centrifugal 30min of 10000 × g, abandoning supernatant, the phosphate buffer that precipitation adds 4ml mixes, and obtains Wistar rat liver mitochondrion concentrate, is experiment monoamine oxidase, MAO.
(2) mensuration of sample to monoamine oxidase inhibitory activity:
Use the inhibition activity of 96 hole ELISA Plate working samples to monoamine oxidase, MAO.In 96 hole ELISA Plate, add successively 40 μ l monoamine oxidase, MAO (Wistar rat liver mitochondrion), 40 μ l sample solutions, 40 μ l iproniazid phosphate solution (positive drug), hatch after 20min for 37 ℃, add 120 μ l substrates (tyramine of 2.5mM) and 40 μ l nitrite ions (the amino antipyrine of 4-of 0.5mM, the vanillic acid of 1mM, the mixture of the horseradish peroxidase of 4U/ml).Hatch after 60min for 37 ℃, under 490nm, measure each hole OD value by microplate reader.Wherein, blank well (comprises: monoamine oxidase, MAO 40 μ l, phosphate buffer 40 μ l, substrate 120 μ l, l), sample well (comprises: monoamine oxidase, MAO 40 μ l developer 40 μ, sample 40 μ l, substrate 120 μ l, l), blank negative hole and iproniazid phosphate control wells replace 120 μ l substrates with 120 μ l phosphate buffers (pH=7.6) to developer 40 μ.Every group of experiment in triplicate, and with the suppression ratio of formula calculation sample to monoamine oxidase, MAO below.
Suppression ratio %=
× 100%
Can calculate the half-inhibition concentration value (IC of sample to monoamine oxidase, MAO according to dose-effect relationship and return law of the straight line
50).It is active that result shows that 3 compounds all have obvious inhibition to monoamine oxidase, MAO.Measure again compound
1-
3half-inhibition concentration value (IC
50), find their IC
50lower, illustrate and there is stronger monoamine oxidase inhibitory activity.Experimental data is in table 1.
Table 1 Sa folding tannin monomer component monoamine oxidase inhibitory activity
Embodiment 3 forced swimming experiments (depressed mouse model)
By the single male SD rat glass cylinder that the depth of water is 15cm (high 40cm diameter 18cm) of putting into, water temperature (24 ± 2) ℃, the depth of water can slightly adjust, and is not enough to again body support is advisable with rat hindleg at the bottom of just can having touched tin.While just putting into, at the bottom of rat forced swimming struggling is climb or slipped into tin, after 2-3min, activity weakens gradually, there is intermittent motionless state, and the time is more and more longer, after 5-6min, the time of motionless state accounts for 80% left and right of total time, and prerun 15 min are dried rat later.Experiment grouping: reject the failure in prerun, 50 qualified rats are divided into 5 groups at random, every group 10, blank group, fluoxetine positive controls gavage every day give normal saline, tested medicine group gavage gives the medicine of corresponding dosage, each group administration volume is 1mL/lO0g, 1 time/d.After gavage 3d, 30min before 4d experiment, except fluoxetine positive controls gavage gives fluoxetine Hydrochloride 85mg/kg, all the other each groups are constant by above-mentioned administration.30min after gastric infusion, with the identical situation of prerun condition under, rat is put into cylinder, observe after 6min record the dead time of rat forced swimming in 4min.Result shows, compound 1, and compound 2, compound 3 all can obviously shorten forced swimming and cause the dead time in depressed mice 4min, can obviously improve the behavioral competence of depressed mice.Experimental data is in table 2.
The impact of table 2 Sa folding tannin monomer component on the depressed mice behavioral competence of forced swimming
*: with relatively P<O.O5 of blank group
Embodiment 4 rotation tests (parkinson rat model)
SD male rat model: be as the criterion with anterior fontanelle, according to work such as bag new people etc. (rat brain stereotaxic atlas [M]. Beijing: People's Health Publisher, 1991:5) rat brain stereotaxic atlas, determine right substantia nigra two place's coordinates: 1. 5.2 mm after bregma, median line right side 1.0mm, 9.0 mm under dura mater; 2. 5.2 mm after bregma, the right 2.5mm of median line, 8.5mm under dura mater.In two coordinate places of place injections 6-OHDA (be dissolved in the normal saline containing ascorbic acid O.02%, concentration is 2g/L, every 3L of place) modeling.Normal group is only fixed rat, does not carry out any processing.Sham operated rats is only injected the equivalent normal saline containing 0.02% ascorbic acid, and all the other conditions are identical with modeling operation.After 10d, bring out animal to strong sideway swivel with APO (0.5mg/kg) through lumbar injection, recording start rotates to the rotating cycle in 30min, take 2-6 circle/min person as qualified minor injury's Parkinson disease model.By 40 of successful modeling SD male rats, be divided at random model group, 1 group of compound (50mg/ml), 2 groups of compounds (50mg/ml), 3 groups of compounds (50mg/ml), 10 every group.Separately include 10 of rats in normal control group in.Wherein compound
1group, compound
2group, compound
3group, gives respectively compound 2mL gavage, and model group, Normal group give equivalent normal saline gavage, continues 45d.After experiment finishes, rats by intraperitoneal injection APO, observes neuroethology and changes.Result shows, compound
1, compound
2, compound
3can obviously shorten 6-OHDA and cause the rotating cycle in parkinson mice 30min, can obviously improve the behavioral competence of parkinson rat.Experimental data is in table 3.
Table 3 Sa folding tannin monomer component causes the impact of parkinson mice behavioral competence on 6-OHDA
?*: with relatively P<O.O5 of model group.
Claims (3)
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