CN107827901A - A kind of Sapidolide A Preparation method and use - Google Patents
A kind of Sapidolide A Preparation method and use Download PDFInfo
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- CN107827901A CN107827901A CN201711081378.9A CN201711081378A CN107827901A CN 107827901 A CN107827901 A CN 107827901A CN 201711081378 A CN201711081378 A CN 201711081378A CN 107827901 A CN107827901 A CN 107827901A
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- China
- Prior art keywords
- sapidolide
- radix baccaureae
- baccaureae ramiflorae
- platymiscium
- preparation
- 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.)
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- OZRZMHKATMSFPV-UHFFFAOYSA-N Sapidolide A Chemical compound O1C(=O)C2C(C=C)C1C1(O)C3(C)C2(O)CCC3CO1 OZRZMHKATMSFPV-UHFFFAOYSA-N 0.000 title claims abstract description 104
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 235000013399 edible fruits Nutrition 0.000 claims abstract description 19
- 210000004185 liver Anatomy 0.000 claims abstract description 13
- 241001529246 Platymiscium Species 0.000 claims abstract description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000033228 biological regulation Effects 0.000 claims abstract description 10
- 239000000741 silica gel Substances 0.000 claims abstract description 10
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000003495 polar organic solvent Substances 0.000 claims abstract description 4
- 238000012545 processing Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- 239000000284 extract Substances 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- 238000000605 extraction Methods 0.000 claims description 10
- 239000003208 petroleum Substances 0.000 claims description 10
- 235000002289 Baccaurea ramiflora Nutrition 0.000 claims description 9
- 241000891306 Baccaurea ramiflora Species 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 8
- 238000010828 elution Methods 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 239000012043 crude product Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- 235000013305 food Nutrition 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 235000012127 Baccaurea motleyana Nutrition 0.000 claims description 2
- 244000266576 Baccaurea motleyana Species 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 210000001367 artery Anatomy 0.000 claims description 2
- 235000013376 functional food Nutrition 0.000 claims description 2
- 235000013336 milk Nutrition 0.000 claims description 2
- 239000008267 milk Substances 0.000 claims description 2
- 210000004080 milk Anatomy 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 210000003462 vein Anatomy 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000006071 cream Substances 0.000 claims 1
- 210000002540 macrophage Anatomy 0.000 abstract description 13
- 230000010287 polarization Effects 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 238000005377 adsorption chromatography Methods 0.000 abstract 1
- 238000000638 solvent extraction Methods 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 9
- 238000011160 research Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 8
- 210000004979 bone marrow derived macrophage Anatomy 0.000 description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229920003266 Leaf® Polymers 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 208000029618 autoimmune pulmonary alveolar proteinosis Diseases 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 229930009674 sesquiterpene lactone Natural products 0.000 description 4
- 150000002107 sesquiterpene lactone derivatives Chemical class 0.000 description 4
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- HATRDXDCPOXQJX-UHFFFAOYSA-N Thapsigargin Natural products CCCCCCCC(=O)OC1C(OC(O)C(=C/C)C)C(=C2C3OC(=O)C(C)(O)C3(O)C(CC(C)(OC(=O)C)C12)OC(=O)CCC)C HATRDXDCPOXQJX-UHFFFAOYSA-N 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- -1 carbocyclic lactone Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229930187829 sapidolide Natural products 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 241001529387 Colletotrichum gloeosporioides Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 235000021028 berry Nutrition 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229930000741 picrotoxane Natural products 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229930004725 sesquiterpene Natural products 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 230000009967 tasteless effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 241001101522 Chiococca Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241001269238 Data Species 0.000 description 1
- 241000221017 Euphorbiaceae Species 0.000 description 1
- 241000202721 Guihaia Species 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- 101000911775 Mus musculus Hsc70-interacting protein Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- CCAZWUJBLXKBAY-ULZPOIKGSA-N Tutin Chemical compound C([C@]12[C@@H]3O[C@@H]3[C@@]3(O)[C@H]4C(=O)O[C@@H]([C@H]([C@]32C)O)[C@H]4C(=C)C)O1 CCAZWUJBLXKBAY-ULZPOIKGSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000011869 dried fruits Nutrition 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 210000001624 hip Anatomy 0.000 description 1
- 210000004394 hip joint Anatomy 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 208000030208 low-grade fever Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000003976 plant breeding Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011122 softwood Substances 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001694 thigh bone Anatomy 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Botany (AREA)
- Mycology (AREA)
- Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a kind of Sapidolide A Preparation method and use.Using the fruit of Radix Baccaureae ramiflorae platymiscium as raw material, in after low polar organic solvent extraction, the sterling that can obtain Sapidolide A is separated and recrystallized through high volume containing the sample silica gel adsorption chromatography.The sterling yield prepared using the technique from raw material is up to more than 0.10%.Proved through pharmacological experiment model discrimination, Sapidolide A play the role of liver protection, promote the polarization of macrophage M2 types, the product immune with regulation available for liver protection is prepared.The present invention develops liver protection and the immune new application of regulation of Sapidolide A in Radix Baccaureae ramiflorae platymiscium, has expanded the medicine sphere of action of Radix Baccaureae ramiflorae platymiscium, foundation is provided for utilization and extention and deep processing Chinese medicine.
Description
Technical field
The invention belongs to medicine food technical field, and in particular to a kind of fruit using Radix Baccaureae ramiflorae platymiscium prepares one as raw material
Kind sesquiterpene lactone monomeric compound Sapidolide A method, and the compound are preparing liver protection function, immunological regulation
Application in the product of function.
Background technology
Radix Baccaureae ramiflorae (Baccaurea ramiflora) belongs to Euphorbiaceae Radix Baccaureae ramiflorae platymiscium, is aiphyllium or shrub, this category
80 kinds are there are about, is distributed in the states such as India, Burma, Vietnam, Laos, China, Hainan, Guangdong, Guangxi, cloud are distributed mainly in China
South.Radix Baccaureae ramiflorae it is tree-like it is unusual it is graceful, it is full of leaves it is evergreen, fruit is colorful beautiful, have old branch yield positive results, dried fruit with reward characteristic garden
Woods landscape value.Radix Baccaureae ramiflorae category is either as excellent dilute tropical fruit (tree), characteristic garden seeds, or is used as the medicinal exploitation of medical treatment,
There is important Development volue.
In the 1970s, former Hainan Technology Bureau composition " Hainan District cancer therapy drug examination group " (Liu Mingsheng Hainan Tropicals
Molecular Plant Breedings, 2003,1 (5) are protected and utilized to resources of medicinal plant:799.) pass through preliminary screening, determine that Radix Baccaureae ramiflorae has
There is the symptom of a trend composition of anticancer；Afterwards, (Xu Jing, Lin Qiang, beam shake the oiling that volatilizees in the Radix Baccaureae ramifloraes such as benefit root, leaf, fruit Xu Jing et al.
The comparative study studied point, Food Science, 2007, (11):439-442.) volatile oil in Radix Baccaureae ramiflorae root, leaf, fruit is carried out
Research and analyse, and they in Radix Baccaureae ramiflorae root isolated one new sesquiterpene lactone table dihydro tutin (Xu Jing,
Guan Huashi, Lin Qiang, wait the new sesquiterpene lactone Chinese herbal medicines in Radix Baccaureae ramiflorae roots, 2007,38 (10):1450-1452.).Give birth in Ningde
Et al. (Ningde is given birth to, Wu Yunfei, Lv Shihong, waits the chemical constitution study GUIHAIAs of Radix Baccaureae ramiflorae cauline leafs, 2014 (2):160-
162.) isolated 8 compounds from the ethyl acetate portion of the stem-leaf extract of Radix Baccaureae ramiflorae, but do not find
Sapidolide A.Indian patent (IN 185385) provides to be extracted from the Baccaurea sapida kinds in Radix Baccaureae ramiflorae category
The method of Sapidolide derivatives.Manobjyoti Bordoloi et al. (Bordoloi M, Barua N C, Mohan S,
et al.Sapidolide A:An unprecedented spherical carbocyclic lactone from
Baccaurea sapida,seed kernels:Is it a meroisoprenoidCheminform,1996,27(51):
Sapidolide A 6791-6792.) are found that from the seed of Radix Baccaureae ramiflorae Baccaurea sapida kinds, but are not provided
Body process and yield.Zheng-Hong Pan et al. (Pan Z H, Ning D S, Huang S S, et al.A new
picrotoxane sesquiterpene from the berries of Baccaurea ramiflora with
antifungal activity against Colletotrichum gloeosporioides.Natural Product
Research,2015,29(14):1323.) the isolated bag from the fruit of Radix Baccaureae ramiflorae Baccaurea ramiflora kinds
Three sesquiterpene lactones including Sapidolide A are included, but its Sapidolide A yield is very low, and step is complicated.This
Outside, folklore has the bark of Radix Baccaureae ramiflorae, pericarp is to boil water for cough-relieving, the tradition relievingd asthma.
We are studied the Radix Baccaureae ramiflorae fruit of two kinds to China, it was found that wherein exist content it is higher into
Point, and it is isolated and purified and identified, determine its structure be Sapidolide A. after we researched and developed and be directed to
The separation purifying technique of this compound, and substantial amounts of Sapidolide A sterlings have been prepared, lived for ensuing pharmacology
Journal of Sex Research provides material base.
In pharmacology activity research, we have first carried out Pharmacological Activity Screening to Radix Baccaureae ramiflorae extract, and we have studied wood
The influence of milk berry extract and the polarization of compounds towards macrophages M2 types, dendritic cells Antigen-presenting role influence, right
The influence of experimental allergic encephalomyelitis (EAE), the influence to Collagen-induced Arthritis (CIA) and to human ovarian cancer
Cell is bred and the influence of transfer.Then Primary mouse macrophage is polarized we have studied the compound on this basis
Influence and the effect to acute liver damage caused by paracetamol, and find that this compound has liver protection and regulation to exempt from first
The function of epidemic disease.The research both at home and abroad to Radix Baccaureae ramiflorae category is not very thorough at present, and Radix Baccaureae ramiflorae category is in medical drugses and health treatment side
There is very big DEVELOPMENT PROSPECT in face.
The content of the invention
It is an object of the invention to provide a kind of Sapidolide A preparation method, is that one kind has liver protection and promotes macrophage
The Sapidolide A of the effect of cell M2 types polarization preparation method, is obtained by following steps：By Radix Baccaureae ramiflorae platymiscium
Full fruit adds the 8-12 times of middle low polar organic solvent measured, room temperature extraction or refluxing extraction by medicinal material/solvent (weight/volume)
2-3 times, the total medicinal extract of gained Radix Baccaureae ramiflorae directly adsorbs with the silica gel mixed sample of 1 to 2 times (weight ratio), then with 0.5 times to 1.5 times of silicon
Mucilage binding enters column chromatography, is eluted through two end number mixing organic solvent, and step purifying can obtain Sapidolide A crude products, then with mixing
Organic solvent recrystallizes, and Sapidolide A sterlings can be prepared.
Use the absorption silica gel of silica gel chromatography：Total medicinal extract (weight ratio) ratio is 2：1 to 1：1；Fill post silica gel：
Total medicinal extract (weight ratio) ratio is 0.5：1 to 1：1.5.
The middle low polar organic solvent of wherein extraction includes：Ethyl acetate, dichloromethane, chloroform, acetone；Elution
Two end number mixing organic solvent be two kinds among petroleum ether, hexane, ethyl acetate, chloroform, dichloromethane, acetone etc. by
20:1 to 2:1 ratio mixes；Mixed organic solvents used in recrystallization be acetone, dichloromethane, chloroform, hexane,
Two kinds in ethyl acetate, petroleum ether and mixed above form.
Wherein the total medicinal extract of Radix Baccaureae ramiflorae can also be by carrying out critical CO to the full fruit of Radix Baccaureae ramiflorae platymiscium2Extraction, 40-60
At a temperature of DEG C, extract 2-3 times, each 2-3 hours are made.
Above-described Radix Baccaureae ramiflorae platymiscium, including Radix Baccaureae ramiflorae Baccaurea ramiflora and more arteries and veins Radix Baccaureae ramifloraes
Baccaurea motleyana。
Sapidolide A provided by the invention preparation method step is simple, and two steps can obtain Sapidolide A's
Sterling, without liquid liquid distribution extraction and common multiple column chromatography steps, reduce it is multiple cross post caused by Sapidolide A damage
Consumption.The yield of this preparation method crude product can reach more than 0.14%, and the yield of sterling can reach more than 0.10%, and document report
(Pan Z H,Ning D S,Huang S S,et al.A new picrotoxane sesquiterpene from the
berries of Baccaurea ramiflora with antifungal activity against
Colletotrichum gloeosporioides.Natural Product Research,2015,29(14):1323.)
It is that big polar solvent extracts with conventional method, middle polar solvent extract, then through means such as silica gel column chromatography, Sephadex LH-20
The yield for preparing Sapidolide A only has 0.019%, and method of the invention can at least improve yield four times.
Sapidolide A property, including UV, IR, MS and NMR are tested by a variety of spectroscopic techniques, is believed to wave spectrum
Confirmation structure is Sapidolide A after breath carries out detailed parsing.Sapidolide A structure is as follows：
It is a further object to provide described Sapidolide A prepare liver protection and the immune medicine of regulation,
Application in the product such as health food or functional food.This research have chosen the C57BL/6 mouse in 8-10 weeks, to Sapidolide
A liver-protecting activity is studied.As a result show that Sapidolide A can substantially reduce the content of AST and ALT in serum.Originally grind
Study carefully a series of Sapidolide A 24h that concentration gradients are acted on derived from bone marrow macrophage (BMDMs).Pass through pharmacology
Experimental model screens, it was demonstrated that it plays the role of liver protection, promotes the polarization of macrophage M2 types, as a result shows, with blank control group phase
Than Sapidolide A can remarkably promote BMDMs M2 (F4/80+CD206+) polarization of type macrophage, available for liver protection and it is immunized
Regulation.
It is provided by the invention that there is liver protection and adjust immunocompetent compound Sapidolide A, it is certain auxiliary by adding
Material, it can apply to prepare the product that liver protection and regulation are immunized.
The present invention develops liver protection and the immune new application of regulation of Sapidolide A in Radix Baccaureae ramiflorae platymiscium, has expanded wood
The medicine sphere of action of milk fruit platymiscium, foundation is provided for utilization and extention and deep processing Chinese medicine, and provide new application side
To.
Brief description of the drawings
Fig. 1 is Sapidolide A1H H NMR spectroscopies (500MHz in d6-CDCl3)。
Fig. 2 is Sapidolide A13C H NMR spectroscopies (125MHz in d6-CDCl3)。
Fig. 3 Sapidolide A mass spectrum.
Fig. 4 Sapidolide A liver-protecting activity results of study.
Fig. 5 Sapidolide A adjust immunocompetence result of study.
Embodiment
The present invention is further described in conjunction with the accompanying drawings and embodiments.
Embodiment 1
Three fresh bifurcation fruits 10.3kg, fruit are divided into several valves, are extracted three times with 80L dichloromethane solution room temperature,
5 days every time.Merge extract solution, steam to tasteless and obtain total medicinal extract 987g.Again by total medicinal extract mix sample in etc. quality 100-200 mesh silicon
Glue, then with etc. quality 100-200 mesh silica gel load chromatographic column, with petroleum ether-ethyl acetate system gradient elution (10:1-5:
1) petroleum ether, is first used：Ethyl acetate 10:1 eluent rinses 130L, then uses petroleum ether：Ethyl acetate 5:1 eluent punching
280L is washed, collects petroleum ether：Ethyl acetate 5:1 elution fraction can obtain Sapidolide A crude products 19g.
Embodiment 2
Three fresh bifurcation fruits 8.6kg, fruit are divided into several valves, use supercritical CO2Abstraction instrument, at a temperature of 40-60 DEG C, carry
Take 2-3 times, each 2-3 hours, obtain total medicinal extract (160g).Total medicinal extract is mixed into sample in the 100-200 mesh silicon of 1.5 times of quality again
Glue, then load chromatographic column with the 200-300 mesh silica gel of 0.5 times of quality, first use n-hexane：Acetone 10:1 eluent rinses 75L,
Then n-hexane is used：Acetone 6:1 eluent rinses 200L, collects n-hexane：Acetone 6:1 elution fraction is i.e. available
SapidolideA crude products 15g.
Embodiment 3
Three dry bifurcation fruits 300g, beat powder, with 3L ethyl acetate solution in 80 degrees Centigrade refluxing extractions three
It is secondary, 3 hours every time.Merge extract solution, steam to tasteless and obtain total medicinal extract, medicinal extract 50g is obtained after drying.Total medicinal extract is mixed into sample in 2 again
The 100-200 mesh silica gel of times quality, the 200-300 mesh silica gel dress post of 1.5 times of quality, first uses petroleum ether：Acetone 12:1 elution
Liquid rinses 6L, then uses petroleum ether：Acetone 6:1 eluent rinses 16L, collects petroleum ether：Acetone 6:1 elution fraction can obtain
To Sapidolide A crude products 600mg.
Embodiment 4
Table 1.Sapidolide A (1) (CDCl3)1H (500MHz) and13C (125MHz) NMR datas and signals assignment
Embodiment 5Sapidolide A liver-protecting activity research
Method：The C57BL/6 mouse in 8-10 weeks are taken, are divided into two groups, every group 3.After overnight fasting (15h or so), abdominal cavity
SA 50mg/kg are given in injection, and control group gives isometric physiological saline.By paracetamol (APAP) in 55 DEG C of water-bath bars
Physiological saline is dissolved under part, is placed in warm water.APAP 350mg/kg are given in 0.5h after SA administrations, intraperitoneal injection.Respectively at
(24h) blood sampling detection Serum ALT, AST value after (0h) and APAP are administered before administration.
Experimental result is shown in accompanying drawing 4, conclusion：Sapidolide A 50mg/kg are given in intraperitoneal injection can be relieved APAP
Caused acute liver damage.
Embodiment 6Sapidolide A regulation immunocompetence research
Experimental method：
(1) separate Primary mouse derived from bone marrow macrophage (Bone Marrow Derived Macrophages,
BMDMs)：
Adult C57BL/6 mouse are taken, neck is taken off and puts to death, 3~5min of immersion in 75% alcohol is placed on, is laid on mouse after taking-up
In sterilization pallet on super-clean bench.The skin between mouse hip joint has carefully been pinched with ophthalmic tweezers, has carefully been cut off with eye scissors
Skin, and two skin of lower extremity are separated, down cut at ankle, up cut at hip, two lower limb for the mouse that dissociates, carefully
Skin is peeled off, thigh and shin bone is cut respectively, cuts off both ends cartilage, expose red marrow chamber.With 5ml syringes, draw former
For macrophage-conditioned media, ossis is gently inserted, is rinsed once with 1.25ml training liquid, can go out most cells, every 4
Only femoral cell is cultivated with a 5ml dish.Last each capsule adds the 50 μ g/ml μ l of M-CSF 5, and culture dish is placed in
37 DEG C, 5%CO2Continuous culture 3 days in incubator.4th day, gently hang down adherent BMDMs with cell scraper and uniformly plant in 6 holes
In plate.After 80% cell attachment, administration.
(2) Sapidolide A administrations and streaming experiment
After cell changes liquid, SA 0,0.5,5,50 μM are given respectively, and culture dish is placed in 37 DEG C, 5%CO2Cultivated in incubator.Medicine
After thing acts on 2 days, cell is collected, after 1 × PBS washings, is resisted under room temperature condition after shaking table closes 1h with 3%BSA and with streaming
Body dyes 1h, and after 1 × PBS washings, cell is resuspended with 500 1 × PBS of μ L, and flow cytomery is used after crossing film.Pass through common dye
The type macrophage of F4/80/CD86 identification of M 1, the type macrophage of F4/80/CD206 identification of M 2, detection macrophage polarization feelings are contaminated altogether
Condition.
Experimental result is shown in accompanying drawing 5, conclusion：Compared with blank control group, Sapidolide A can remarkably promote BMDMs M2
(F4/80+CD206+) type macrophage, but BMDMs M1 (F4/80 are not influenceed+CD86+) type macrophage, and low dosage promotees M2
Type polarization becomes apparent.
The preparation of embodiment 7Sapidolide A pills
Precision weighs 50g Sapidolide A, adds appropriate absolute ethyl alcohol, and low-grade fever dissolves, and is added to 375g PEG4000
In fused solution, it is uniformly mixed, until ethanol is waved to the greatest extent, is statically placed in 90 DEG C of water-baths and is incubated 30min.Treat that bubble eliminates, protecting
Under conditions of temperature, fused mass is drawn with 1.6mm syringe, control drop is away from the range of 6~8cm, and cooling height is 15cm, drop
To be condensed in 5 DEG C of condensate liquid atoleines of people incline condensate liquid completely, collects dripping pill, drip is net and is removed with filter paper on dripping pill
Condensate liquid, produce.Per grain ball A containing Sapidolide 700mg.
The preparation of embodiment 8Sapidolide A tablets
Sapidolide A 1kg and starch 1kg is mixed, and adds 10% starch slurry 300g that softwood is made, and adds magnesium stearate
20g, dried starch 18g are pressed into 2000 after mixing, and produce.The every 500mg of A containing Sapidolide.
Claims (5)
1. a kind of Sapidolide A preparation method, it is characterised in that realized by following steps：By Radix Baccaureae ramiflorae platymiscium
Full fruit is that weight/volume adds the 8-12 times of middle low polar organic solvent measured, room temperature extraction or refluxing extraction by medicinal material/solvent
2-3 times, the total medicinal extract of gained Radix Baccaureae ramiflorae directly fills with weight than the silica gel mixed sample absorption for 1-2 times, then with 0.5-1.5 times of silica gel
Enter column chromatography, eluted through two end number mixing organic solvent, a step purifies to obtain Sapidolide A crude products, then organic molten with mixing
Agent recrystallizes, and Sapidolide A sterlings are prepared.
A kind of 2. Sapidolide A according to claim 1 preparation method, it is characterised in that low pole in extraction
Property organic solvent select：Ethyl acetate, dichloromethane, chloroform, acetone；The two end number mixing organic solvent of elution is oil
Two kinds in ether, hexane, ethyl acetate, chloroform, dichloromethane, acetone are pressed 20:1 to 2:1 ratio mixes；Recrystallization institute
The mixed organic solvents used be acetone, dichloromethane, chloroform, hexane, ethyl acetate, two kinds in petroleum ether and mixed above
Form.
3. a kind of Sapidolide A according to claim 1 preparation method, it is characterised in that wherein Radix Baccaureae ramiflorae always soaks
Another processing of cream is by carrying out supercritical CO to the full fruit of Radix Baccaureae ramiflorae platymiscium2Extract, at a temperature of 40-60 DEG C, extraction
2-3 times, each 2-3 hours are made.
A kind of 4. preparation method of Sapidolide A according to claim 1 or 3, it is characterised in that described wooden milk
Fruit platymiscium, including Radix Baccaureae ramiflorae Baccaurea ramiflora and more arteries and veins Radix Baccaureae ramiflorae Baccaurea motleyana.
5. the Sapidolide A that according to claim 1 prepared by method are preparing medicine, the health care that liver protection and regulation are immunized
Application in the product such as food or functional food.
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| CN113633702A (en) * | 2021-09-13 | 2021-11-12 | 云南中医药大学 | Dai medicine composition for relieving senile cutaneous pruritus and preparation and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN185385B (en) * | 1996-08-23 | 2001-01-13 | Council Of Scient & Ind | |
| CN106422403A (en) * | 2016-09-27 | 2017-02-22 | 桂林茗兴生物科技有限公司 | Preparation method of Baccaurea ramiflora extract |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN185385B (en) * | 1996-08-23 | 2001-01-13 | Council Of Scient & Ind | |
| CN106422403A (en) * | 2016-09-27 | 2017-02-22 | 桂林茗兴生物科技有限公司 | Preparation method of Baccaurea ramiflora extract |
Non-Patent Citations (3)
| Title |
|---|
| MANOBJYOTI BORDOLOI等: "Sapidolide A: An Unprecedented Spherical Carbocyclic Lactone from Baccaurea sapida Seed Kernels : Is It a Meroisoprenoid ?", 《TETRAHEDRON LETTERS》 * |
| ZHENG-HONG PAN等: "A new picrotoxane sesquiterpene from the berries of Baccaurea ramiflora with antifungal activity against Colletotrichum gloeosporioides", 《NATURAL PRODUCT RESEARCH》 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113633702A (en) * | 2021-09-13 | 2021-11-12 | 云南中医药大学 | Dai medicine composition for relieving senile cutaneous pruritus and preparation and application thereof |
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