CN103980198B - Alkaloid Casuarinine H and the purposes in preparation treatment nerve degenerative diseases medicine thereof - Google Patents

Alkaloid Casuarinine H and the purposes in preparation treatment nerve degenerative diseases medicine thereof Download PDF

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CN103980198B
CN103980198B CN201310051286.1A CN201310051286A CN103980198B CN 103980198 B CN103980198 B CN 103980198B CN 201310051286 A CN201310051286 A CN 201310051286A CN 103980198 B CN103980198 B CN 103980198B
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casuarinine
alkaloid
extract
rattan
lycopod
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CN103980198A (en
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胡金锋
杨国勋
唐宇
熊娟
胡长玲
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Fudan University
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Fudan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/22—Bridged ring systems

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  • Organic Chemistry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

nullThe invention belongs to pharmaceutical technology field，Relate to alkaloid Casuarinine H and new medical use thereof in rattan lycopod extract，It is specifically related to alkaloid Casuarinine H purposes in preparation treatment nerve degenerative diseases medicine in rattan lycopod extract，The present invention passes through oxidative stress in-vitro screening model，Alkaloid Casuarinine H in rattan lycopod extract has been carried out activity research，Experiment display，The cellular damage that oxidative stress is caused by alkaloid Casuarinine H has significant protective effect，Described alkaloid Casuarinine H can be used alone or share，Or be combined with suitable excipient，Conventionally make oral or non-oral dosage forms，As made tablet、Capsule、Particle or injection，It is applied to the medicine of preparation treatment nerve degenerative diseases，Include but not limited to Alzheimer disease or Parkinson's disease etc..

Description

Alkaloid Casuarinine H and the purposes in preparation treatment nerve degenerative diseases medicine thereof
Technical field
The present invention relates to pharmaceutical technology field, relate to alkaloid Casuarinine H and new medical use thereof in rattan lycopod extract, it is specifically related to alkaloid Casuarinine H purposes in preparation treatment nerve degenerative diseases medicine in rattan lycopod extract, particularly relate to alkaloid Casuarinine H purposes in the nerve degenerative diseases medicines such as preparation treatment Alzheimer disease, Parkinson's disease, ALS in rattan lycopod extract, present invention simultaneously relates to Casuarinine H methods of extraction and preparation from rattan lycopod.
Background technology
Research display, nerve degenerative diseases such as Alzheimer disease (Alzheimer's disease, AD), Parkinson's disease (Parkinson'sdisease, PD), ALS (Amyotrophic lateralsclerosis, ALS), Huntington disease (Huntington'sdisease, etc. HD) not only have a strong impact on the quality of life of patient, and bring the biggest financial burden to society.Although at present can't the pathogenesis of those character various disease of clear interpretation, but, substantial amounts of research data shows, in those nerve degenerative diseases, the nerve cell in specific brain regions district is attacked by active oxygen radical (Reactive Oxygen Species, ROS), makes apoptosis, and then deteriorate until neuroid dysfunction, finally there is nerve degenerative diseases.Research also show, ROS-oxidative stress (Oxidative Stress, OS) nerve degenerative diseases is apoptotic develop in play an important role.Therefore, eliminate or reduce the oxidation of free radical and can will effectively alleviate or delay the symptom of nervus retrogression patient.
Prior art discloses relevant Chinese herbal medicine and show multicomponent, Mutiple Targets, hypotoxic unique advantage in terms for the treatment of nerve degenerative diseases.As, there are the classical prescription of some Chinese herbal medicines, proved recipe to obtain relatively successful Application clinically.
Rattan lycopod (Lycopodiastrum casuarinoides(Spring) Holub.) it is Lycopodiaceae rattan Lycopodium plant, it is distributed mainly on the ground such as south China, southwest and Hubei, Hunan, Fujian, Taiwan, among the people with all herbal medicine, it is mainly used in treating rheumatic arthritis, traumatic injury, arthralgia and myalgia etc..Nineteen nineties, the chemical composition of this plant is studied by the scientific research personnel of China first, therefrom find that there are three the lycopodine compounds similar with huperzine (Huperzine A) skeleton structure: huperzinine (Huperzinine), Huperzine C and Huperzine D, and the acetylcholinesteraseinhibition inhibition of Huperzine C is suitable with huperzine.
So far, there is not yet about alkaloid Casuarinine H in rattan lycopod extract at the report preparing the purposes treated in nerve degenerative diseases medicine.
Summary of the invention
It is an object of the invention to provide alkaloid Casuarinine H and new medical use thereof in rattan lycopod extract, it is specifically related to alkaloid Casuarinine H and the purposes in preparation treatment nerve degenerative diseases medicine thereof in rattan lycopod extract, particularly relates to alkaloid Casuarinine H purposes in the nerve degenerative diseases medicines such as preparation treatment Alzheimer disease, Parkinson's disease, ALS in rattan lycopod extract.
The present invention passes through oxidative stress in-vitro screening model; the multiple chemical composition derived from Chinese herbal medicine has been carried out activity research; experiment display; alkaloid Casuarinine H in rattan lycopod has obvious biological significance: the cellular damage that oxidative stress is caused by this alkaloid has significant protective effect; under 10 μMs of concentration, Casuarinine H is to H2O2Human neuroblastoma cells (SHSY-5Y) damage of induction can produce significant protective effect；Further; described alkaloid Casuarinine H can be used alone or share, or is combined with suitable excipient, conventionally makes oral or non-oral dosage forms; as made tablet, capsule, particle or injection, it is applied to the medicine of preparation treatment nerve degenerative diseases.
The invention provides the preparation method of alkaloid Casuarinine H in rattan lycopod extract,
Described active component Casuarinine H is prepared via method conventional involved by this area by rattan lycopod aerial part or its herb, it includes step: first with rattan lycopod aerial part or rattan lycopod herb as raw material, use solvent extraction method to make concentrated extract；In the solvent extraction method used, single solvent or the mixing solvents of multi-solvents such as water, methyl alcohol, ethanol, acetone can be selected, it is optimum extraction solvent with 50 ~ 95% ethanol, at room temperature refluxing extraction under Soakage extraction or heating condition, extraction time is 2～3 times, extract is suspended in appropriate 3% aqueous tartaric acid solution after concentrating, and extracts 2～3 times with isopyknic ethyl acetate；Aqueous tartaric acid solution is with Na2CO3Regulation pH value is to 10, then extract with chloroform, obtain TA (chloroform extract), through column chromatography, monomeric compound Casuarinine H it is prepared into from rattan lycopod chloroform extract, named Casuarinine H, bioactivity research shows that this compound is the direct active material of rattan lycopod extract opposing oxidative stress, passes through1H-NMR, 13C-NMR, 2D-NMR and MS, it is determined that the chemical constitution of this compound such as formula I:
Compound: Casuarinine H, [α]22.5D-17.1°(c0.65,CHCl3)。1H-NMR(400MHz, CDCl3null): δ 6.44 (1H,d,J=9.2Hz,H-2),7.76(1H,d,J=9.2Hz,H-3),3.06(1H,dd,J=18.8,7.1Hz,H-6α),2.51(1H,br d,J=18.8Hz,H-6β),2.30(1H,m,H-7),1.29(1H,ddd,J=12.8,12.7,3.7Hz,H-8α),1.75(1H,br d,J=12.8Hz,H-8β),5.23(1H,dd,J=16.8,1.8Hz,H-10a),5.14(1H,dd,J=10.4,2.0Hz,H-10b),5.62(1H,ddd,J=16.8, 10.4,9.6Hz,H-11),2.14(1H,dd,J=9.6,2.9Hz,H-12),1.09(1H,dd,J=12.0,12.0Hz,H-14a),1.64(1H,dd,J=12.0,3.9Hz,H-14b),1.40(1H,m),0.85(3H,d,J=6.4,Me-16),13.30(1H,br s,NH)。13C-NMR(100MHz,CDCl3):δ164.9(C-1),118.9(C-2),140.3(C-3),120.5(C-4),143.7(C-5),29.9(C-6),34.2(C-7),42.5(C-8),117.2(C-10),137.3(C-11),49.9(C-12),54.8(C-13),52.2(C-14),26.3(C-15),21.7(C-16);(+)ESI-MS m/z245[M+H]+,267[M+Na]+,511[2M+Na]+;(+)HR-ESI-MS m/z245.1649[M+H]+(calcd for C15H21N2O,245.1648).
The present invention carries out the research display of external oxidative stress screening model further, and the cellular damage that oxidative stress is caused by this alkaloid has significant protective effect.Therefore, Casuarinine H can be used alone or share with other drug, or is combined with suitable excipient, conventionally makes oral or non-oral dosage forms and is applied to the treatment of nerve degenerative diseases.
The invention have the advantage that Casuarinine H is the noval chemical compound found first, there is chemical constitution novelty；Casuarinine H has application prospect to nerve degenerative diseases, the Alzheimer disease and the Parkinson's disease that especially have a strong impact on life of elderly person quality；Rattan lycopod is widely distributed in China, and ABUNDANT NATUREAL RESOURSES is cheap and easy to get；Rattan lycopod belongs to herbaceous plant, and power of regeneration is strong, even if carrying out large-scale production also do not result in resource exhaustion.
Accompanying drawing explanation
Fig. 1 is the neuroprotection activity data result of alkaloid Casuarinine H,
Wherein, Y value is cell survival rate, represents by mean value (Mean) ± standard deviation (SD), and Normal group survival rate is set to 100%, and remaining is respectively organized is the percentage value compared with normal group,##P < 0.01 is compared to Normal group；* p < 0.05, * * p < 0.01 is compared to H2O2Damage group, ACETYLCYSTEINE (n-acetyl-L-cysteine, L-NAC) is positive control.
Detailed description of the invention
With embodiment, the present invention is further elaborated below, but these embodiments have absolutely not any restriction to the present invention.Any variation that those skilled in the art are made in implementing the present invention under the enlightenment of this specification all will fall within the scope of the appended claims.
Embodiment 1
Rattan lycopod herb 1kg, pulverizes, with the 90% methyl alcohol room temperature cold soaking 24 hours of 3 times amount, and totally 3 times.Merge No. 3 extracts, reduced pressure concentration, obtain 90g medicinal extract.Medicinal extract 3% aqueous tartaric acid solution suspendible of 2 times amount, carries out extracting three times with ethyl acetate isopyknic with suspension, then uses Na2CO3Aqueous tartaric acid solution part is adjusted to pH=10, extract three times with chloroform again, chloroform extraction part reduced pressure obtains alkaloid total medicinal extract 1.1g after concentrating, then sample is mixed with equimultiple silica gel (100～200 mesh), column chromatography is carried out, with dichloromethane: methyl alcohol is as eluent gradient wash-out wash-out (volume ratio 1:0-0:1) with the silica gel (200～300 mesh) of 50 times amount.Collect dichloromethane: methyl alcohol (15:1, volume ratio) elution fraction, this component continued silicagel column, used dichloromethane: methyl alcohol 50:1,30:1,10:1 elute.30:1 elution fraction uses preparation HPLC be purified, with methyl alcohol: water: diethylamine (35:65:0.05%) isocratic elution, collect 39.524min component, obtain 15mg white amorphous powder Casuarinine H.
Embodiment 2
Rattan lycopod herb 1kg pulverizes, and refluxes 3 hours with under 80% ethanol room temperature, is repeated 3 times, and merges extract, and reduced pressure concentration obtains medicinal extract 110g.Medicinal extract 3% aqueous tartaric acid solution suspendible of 2 times amount, extracts three times with ethyl acetate isopyknic with suspension, then uses Na2CO3Aqueous tartaric acid solution is adjusted to pH=10, extracts three times with equal-volume chloroform.Chloroform extraction part reduced pressure obtains alkaloid total medicinal extract 1.3g after concentrating.Macroreticular resin HP-20 on medicinal extract, respectively with water, 50% ethanol, 90% ethanol elution, by Sephadex LH-20 in 50% ethanol elution part, uses dichloromethane: methyl alcohol 2:1 elutes, and is obtained the Casuarinine H of 13mg by TLC combining data detection.
The neuroprotection test of embodiment 3Casuarinine H
SHSY-5Y cell, after digestion, is suspended from the MEM/F12 nutrient solution containing 10% hyclone.With 2 × 105SHSY-5Y cell is inoculated on 96 well culture plates by the density of individual/milliliter, and inoculation volume is 100 microlitres/hole, is subsequently placed in containing 5%CO237 DEG C of constant incubators in cultivate 24 hours.The nutrient solution in each hole is changed into fresh MEM/F12 nutrient solution, administration group adds the testing compound (10 microlitres/hole) of respective concentration, Normal group and H2O2Damage group adds compound solvent comparison (10 microlitres/hole).After hatching 2 hours, at administration group and H2O2Damage group is separately added into 1mM H2O2(10 microlitres/hole), final concentration of 100 μMs.After continuing to cultivate 24 hours, add 5mg/mL MTT(10 microlitre/hole), carry out living cells dyeing.After hatching 3 hours, discard nutrient solution, add 100%DMSO(100 microlitre/hole), and shaking is allowed to fully dissolve on rocker machine.Measuring the OD value of each group under the wavelength of 490nm, result of the test display Casuarinine H has significant protective effect to SHSY-5Y oxidativestress damage.As it is shown in figure 1, wherein, Hu JF-8 represents embodiment 1 gained rattan lycopod activity extract Casuarinine H to the activity data of Casuarinine H.

Claims (6)

1. the alkaloid Casuarinine H compound of Formulas I is in preparation treatment nervus retrogression disease Purposes in medicine,
2. the purposes as described in claim 1, wherein said nerve degenerative diseases is Ah Alzheimer's disease or Parkinson's disease or ALS.
3. a preparation method of alkaloid Casuarinine H, described alkaloid Casuarinine H is prepared by following method: with rattan lycopod aerial part or rattan lycopod herb as raw material, uses Solvent extraction method makes concentrated extract；The solvent used is selected from water, methyl alcohol, ethanol or third The mixing solvent of ketone single solvent or multi-solvents, under room temperature, Soakage extraction or heating condition are next time Stream extracts, and extraction time is 2～3 times, and extract is suspended in appropriate 3% winestone sour water after concentrating In solution, extract 2～3 times with isopyknic ethyl acetate；Aqueous tartaric acid solution is with Na2CO3 Regulation pH value, to 10, then extracts with chloroform, it is thus achieved that chloroform extract, through column chromatography, from Chloroform extract prepares monomeric compound Casuarinine H, determines the chemistry knot of this compound Structure such as Formulas I:
4. the preparation method as described in claim 3, it is characterised in that described preparation method The Extraction solvent of middle employing is 50～95% ethanol.
5. the purposes according to claim 1, it is characterised in that described Casuarinine H is mono- Solely apply or share with other drug.
6. by the purposes of claim 1, it is characterised in that described Casuarinine H with Excipient combines and makes tablet, capsule, particle or injection.
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CN107365316B (en) * 2017-08-01 2019-07-26 中国科学院昆明植物研究所 Lycopodium alkaloid lycoplanineA and its pharmaceutical composition and preparation method and application
CN114392260A (en) * 2022-02-15 2022-04-26 重庆市九龙坡区精神卫生中心(重庆市九龙坡区石坪桥医院) Medicine for relieving anxiety and depression

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101732312A (en) * 2009-11-27 2010-06-16 武汉益维康医药技术开发有限公司 Huperzine A oral formulation and a preparation method thereof
CN102151268A (en) * 2011-03-28 2011-08-17 王义明 Compound preparation for treating Alzheimer's disease and preparation method thereof
CN102178680A (en) * 2011-04-24 2011-09-14 浙江现代中药与天然药物研究院有限公司 Long-acting and high-content Huperzine paster and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101732312A (en) * 2009-11-27 2010-06-16 武汉益维康医药技术开发有限公司 Huperzine A oral formulation and a preparation method thereof
CN102151268A (en) * 2011-03-28 2011-08-17 王义明 Compound preparation for treating Alzheimer's disease and preparation method thereof
CN102178680A (en) * 2011-04-24 2011-09-14 浙江现代中药与天然药物研究院有限公司 Long-acting and high-content Huperzine paster and preparation method thereof

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