CN104435019A - Novel pharmaceutical application of mangosteen shell extract - Google Patents
Novel pharmaceutical application of mangosteen shell extract Download PDFInfo
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- CN104435019A CN104435019A CN201310447244.XA CN201310447244A CN104435019A CN 104435019 A CN104435019 A CN 104435019A CN 201310447244 A CN201310447244 A CN 201310447244A CN 104435019 A CN104435019 A CN 104435019A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Abstract
The invention discloses a novel pharmaceutical application of a mangosteen shell extract. The mangosteen shell extract is applied to preparation of the following products: (1) a product for preventing and/or treating the Parkinson disease; (2) a product for preventing and/or treating the degenerative change of dopaminergic neuron dendrites of a patient suffering from the Parkinson disease; (3) an oxidative-stress-resistant product; and (4) a product for preventing and/or treating oxidative stress of the Parkinson disease. Pharmacodynamic experiments prove that the mangosteen shell extract can be used for recovering (parts of) dopaminergic neuron dendrites of a nematode model suffering from the a30p Parkinson disease, and can also be used for inhibiting the level of reactive oxygen in the nematode model suffering from the Parkinson disease induced by rotenone. Furthermore, the mangosteen shell extract is proved to have relatively good Parkinson disease resistance and oxidative stress resistance.
Description
Technical field
The present invention relates to a kind of new medicine use of Carcinia mangostana L. shell extract.
Background technology
Parkinson disease (Parkinson ' s disease, PD) be only second to Alzheimer (Alzheimer ' s disease, AD) second largest neurodegenerative diseases, it is a kind of nigrostriatum system dopamine (dopamine, DA) a kind of chronic disease of the impaired caused dopamine of function of nervous system and acetylcholine dysequilibrium, with bradykinesia, static tremor and tetanic for principal character.The PD cause of disease is not bright so far, may be relevant with old, environmental factors and inherited genetic factors, its pathogenesis also relates to free radical, oxidative stress, glutamate excitotoxicity, mitochondrial complex I disappearance, inflammation, neurotrophic factor shortage and apoptosis etc., and in cascade biochemical reaction, these mechanism interact and finally cause neuronal death.
In recent years, rotenone model changes and all pathological characteristicses and enjoy Chinese scholars to pay close attention to due to the behavioristics can reproducing PD simultaneously, and the model that rotenone is induced is closer to mankind PD symptom.Rotenone derives from the natural product in plant, rotenone has extremely strong lipotropy, freely organelle is gathered in as in mitochondrion by blood brain barrier and cell membrane when not relying on DA transporter, be the uncoupling agents of Mitochondria, specificity suppresses the composite I in respiratory chain.The alternative activity of mitochondrial complex I that suppresses produces active oxygen and release apoptosis inducible factor, causes oxidative stress and apoptosis.Experiment confirms that low dosage is chronic and gives the PD symptom that rotenone can cause animal.
α-synuclein is considered to play central role in parkinson disease pathogenic process, shows: 1) α-synuclein mutant A53T, A30P, E46K is out identified in different parkinson disease family; 2) α-synuclein albumen is the main component of parkinson patient Lewy corpusculum.α-synuclein gene mutation may be relevant with the neuronic degeneration of family parkinson patient nigrostriatal dopamine, so, people utilize transgenic technology, and being wild type or mutant ' alpha '-synuclein in mice or model organism are as fruit bat, Caenorhabditis elegans, overexpression prepares animal model to study pathogenesis of Parkinson disease or mechanism of drug action.Nematicide Parkinson disease model (the Kuwahara T. that the nematicide PD model (being called for short A30P) turning people α-synuclein mutant gene (mutational site A30P) is prepared from by people such as Japanese Tomoki Kuwahara, Koyama A., Gengyo-Ando K., et al. (2006) .Familial Parkinsonmutant alpha-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditiselegans [J] .J Biol Chem281 (1): 334-340).
Nematicide has accurate anatomical structure, fast replicative cycle, brief life cycle and translucent cell space (http://www.wormbook.org/).Though nematicide is little, various environmental stimulus (contact, temperature, chemical substance, ion, pheromone etc.) can be experienced, and make all reactions by Coordinating Muscle motion, go after profits and advoid disadvantages to complete, take food, discharge feces, the behavior such as copulation.Also evidence suggests that the associative memory of nematicide can keep more than one day.Be easy to regulate its gene expression by gene silencing or the means such as to knock out.Can directly to specific neuronal isoform, as dopaminergic neuron carries out transgenic intervention.Easily realize observing neuronic integrity in living nematode by fluorescence indicator, and can observe until it is old and feeble from larval stage always.These features make nematicide become the powerful model organism of research diseases associated with senescence.Dopamine neuron emphasis on cell and molecular level of nematicide embodies the feature of mammals dopamine neuron.But be different from vertebrates and contain up to ten thousand dopamine neurons, hermaphroditic nematicide only has 8 dopamine neurons, be easy to observe.Wherein 6 are positioned at large front end, are made up of two pairs of CEP (cephalic) and a pair ADE (anterior deirid) neuron.Afterbody also has two PDE(posterior deirid) neuron.They show the enzymatic activity of all mammals and dopamine biosynthesis, storage, transhipment and transmission of signal.
Garcinia mangostana (Garcinia mangostana) has another name called Cortex Garciniae, mangosteen, garcinia mangostana, is the fruit of Guttiferae Garcinia aiphyllium Garcinia mangostana, originates in torrid areas, Nan Yang, has the title of " after the fruit of the torrid zone ".Containing a large amount of crude fibre, pectin, plant polyphenol in outer peel, can be used as medicine.The clinical practice at home of Garcinia mangostana outer peel is considerably less, and as the traditional medicine of the countries in Southeast Asia such as Thailand, Burma, India, Garcinia mangostana outer peel has been widely used in disease treatment and antiulcer, antiinflammatory, leukemia and the septicemia etc. such as treatment stomachache, diarrhoea, dysentery, infected wound, suppuration, chronic ulcer.20 century 70s, external insider has in succession found a series of new chemical composition and very valuable bioactive ingredients in Garcinia mangostana outer peel.Research finds that Garcinia mangostana has antioxidant activity, the effect of enhancing human body immunity power, antiinflammatory and the effect such as anti-allergic effects, the effect of enhancing human body immunity power.Not yet have at present and Carcinia mangostana L. shell extract is used for the treatment of Parkinsonian relevant report.
Summary of the invention
The object of this invention is to provide a kind of new medicine use of Carcinia mangostana L. shell extract.
The new medicine use of Carcinia mangostana L. shell extract provided by the present invention is that it is preparing the application prevented and/or treated in Parkinsonian product.Described parkinson disease comprise Primary ventricular hemorrhage medicine and Secondary cases parkinson disease.
Further, present invention also offers Carcinia mangostana L. shell extract and prepare the application prevented and/or treated in the product of the degeneration of parkinson patient dopamine neuron dendron; Carcinia mangostana L. shell extract is preparing the application in anti-oxidation stress product; And Carcinia mangostana L. shell extract is preparing the application prevented and/or treated in the product of parkinson disease oxidative stress.
The said goods includes medicine and health product.
The shell extract of Carcinia mangostana L. described in the present invention is the effective ingredient extracted from the dry shell of Garcinia mangostana.The routine operation that its extracting method can adopt state of the art to extract Garcinia mangostana shell, 80 ~ 95% ethanol waters that volume fraction also can be adopted to be carry out reflux, extract, process to Garcinia mangostana shell, collect backflow, through concentrating and obtaining Carcinia mangostana L. shell extract after drying.
In said extracted method, Garcinia mangostana shell first can carry out pretreatment before extraction: after being cleaned up by Garcinia mangostana shell, and 60 DEG C are dried to constant weight, is used for the extraction in later stage after the Garcinia mangostana shell of drying is broken into pieces with one's fingers or pulverized.
Concrete extracting method is as follows: 80 ~ 95% ethanol waters that Garcinia mangostana shell volume fraction is are carried out reflux, extract, collects backflow and concentrates, by the concentrated solution vacuum drying obtained, obtaining Carcinia mangostana L. shell extract; Described backflow, concentrated and drying are the routine operation of this area.
Described reflux, extract, is at least carried out once, preferably extracts 2 times, and each time of extracting can be 1-2 hour; During each extraction, the proportioning of Extraction solvent and described Garcinia mangostana shell is 8-10L:1kg.
That prepares for effective ingredient with Carcinia mangostana L. shell extract prevents and/or treats Parkinsonian medicine and/or health product, also belongs to protection scope of the present invention.
Described prevent and/or treat Parkinsonian medicine by oral, injection, spray, infiltration, absorb, physics or chemistry mediation method import body as muscle, Intradermal, subcutaneous, vein, mucosal tissue; Or to be mixed by other materials or to import body after wrapping up.
With the medicine that Carcinia mangostana L. shell extract is effective ingredient, when needs, one or more pharmaceutically acceptable carriers can also be added in said medicine.Described carrier comprises the diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant etc. of pharmaceutical field routine.The administering mode of described medicine can be but be not limited to the modes such as oral, quiet note, intramuscular injection, and its dosage form can make the various ways such as injection, tablet, powder, granule, capsule, oral liquid.The medicine of above-mentioned various dosage form all can be prepared according to the conventional method of pharmaceutical field.
Pharmacodynamic experiment shows, Carcinia mangostana L. shell extract can make A30P parkinson disease nematode model dopamine neuron dendron (part) recover; Reactive oxygen species in the parkinson disease nematode model body that rotenone simultaneously also can be suppressed to induce.And then prove, described Carcinia mangostana L. shell extract has the effect of good anti-parkinson effect and anti-oxidation stress, and its single taking dose scope is 1 ~ 200mg/kg.
Accompanying drawing explanation
Fig. 1 is the intervention effect of Carcinia mangostana L. shell extract to A30P nematicide Parkinson disease model, * * * compared with matched group, P<0.001.
Fig. 2 is for Carcinia mangostana L. shell extract is to N caused by rotenone
2the inhibitory action (RFU represents Relative fluorescence units) that nematicide active oxygen raises; $ $ $ rotenone vs. matched group, p<0.001; * * Carcinia mangostana L. shell extract vs. rotenone, p<0.001.
Detailed description of the invention
Below by specific embodiment, the present invention will be described, but the present invention is not limited thereto.Experimental technique described in following embodiment, if no special instructions, is conventional method; Described reagent and biomaterial, if no special instructions, all can obtain from commercial channels.
Experiment material used in following embodiment is as follows
1, nematicide strain: bacterial strain E.coli OP50, Wild-type C. elegans Bristol (N
2) (list of references: Brenner, S.The genetics of Caenorhabditis elegans [J] .Genetics, 1974,77:71 – 94); Turn nematicide PD model (being called for short the A30P) (list of references: Kuwahara T. of people α-synuclein mutant gene (mutational site A30P), KoyamaA., Gengyo-Ando K., et al. (2006) .Familial Parkinson mutant alpha-synuclein causes dopamineneuron dysfunction in transgenic Caenorhabditis elegans [J] .J Biol Chem281 (1): 334-340)
2, medicine and reagent: agar powder (Nippon Union K. K), peptone, tryptone(OXOID), rotenone and DHR123(sigma), all the other reagent are domestic.
Statistical analysis: adopt ANOVA variance test to analyze pharmaceutical intervention experimental result, quantitative data with
represent; Adopt two sample t method of inspection comparative analysis group differences.
The Carcinia mangostana L. shell extract used in following embodiment is prepared as follows and obtains: after being cleaned up by Garcinia mangostana shell, and 60 DEG C are dried to constant weight, weigh and obtain 3kg; Broken into pieces with one's fingers by the Garcinia mangostana shell of drying, adding volume fraction is that the alcoholic solution of 95% is respectively with the ratio of 1:10,1:8 (kg/L) reflux, extract, 2 times, each extraction time is 1.5 hours, collect backflow and concentrated, by the concentrated solution vacuum drying that obtains 24 hours, obtain vacuum drying extract; Described backflow, concentrated and drying are the routine operation of this area.
Embodiment 1, Carcinia mangostana L. shell extract affect nematicide cellar culture to A30P parkinson disease nematode model dopamine neuron dendron:
Model group A30P nematicide, is inoculated in the standard nematode culture medium (nematode growthmedium, NGM) of coating E.Coli OP50 in 20 DEG C of constant temperature culture.
Pharmaceutical intervention is tested:
Synchronization: young adult is washed till in aseptic EP pipe with M9 buffer solution, add appropriate lysate (0.5% sodium hypochlorite, 0.5N sodium hydroxide) cracking nematicide, put centrifugal (3000rpm, 1min) on low speed centrifuge, abandon supernatant, nematicide is rinsed 2 times again with M9 buffer solution, centrifugal abandon supernatant after draw nematicide bottom EP pipe with pipettor and drip the aseptic area in NGM, the germ cell in the nematicide body of cracking after about 48 hours develops into L4 phase larva substantially, completes synchronization and tests for next step.
Synchronized nematicide is inoculated in each group of culture medium, 20 DEG C of constant temperature culture 3 days, the Carcinia mangostana L. shell extract (1mg/ml and 0.1mg/ml) adding variable concentrations is intervened, 20 DEG C of constant temperature culture 4 days, the young adult of picking puts fluorescence microscopy Microscopic observation, statistics dopamine neuron dendron (part) recovers nematicide ratio, the results are shown in Figure 1.More than experiment independently repeats once.As shown in Figure 1, after 1mg/ml Carcinia mangostana L. shell extract intervenes nematicide A30P PD model, compared with matched group, there is ratio apparently higher than matched group (P < 0.001) in dopamine dendron disappearance phenotype nematicide.
Embodiment 2, Carcinia mangostana L. shell extract affect nematicide cellar culture to rotenone induction parkinson disease nematode model activity in vivo oxygen level:
Wild-type C. elegans N
2, be inoculated in the standard nematode culture medium (nematodegrowth medium, NGM) of coating E.Coli OP50 in 20 DEG C of constant temperature culture.
Pharmaceutical intervention is tested:
Synchronization: young adult is washed till in aseptic EP pipe with M9 buffer solution, add appropriate lysate (0.5% sodium hypochlorite, 0.5N sodium hydroxide) cracking nematicide, put centrifugal (3000rpm, 1min) on low speed centrifuge, abandon supernatant, nematicide is rinsed 2 times again with M9 buffer solution, centrifugal abandon supernatant after draw nematicide bottom EP pipe with pipettor and drip the aseptic area in NGM, the germ cell in the nematicide body of cracking after about 48 hours develops into L4 phase larva substantially, completes synchronization and tests for next step.
Synchronized nematicide is inoculated in each group of culture medium, 20 DEG C of constant temperature culture 3 days, add 25 μMs of rotenone induction nematicide PD models, the Carcinia mangostana L. shell extract (1mg/ml and 0.1mg/ml) simultaneously adding variable concentrations is intervened, after 24h, with M9 buffer solution cleaning nematicide, adding final concentration is that 100 μMs of DHR123 (dihydro Rhodamine 123) at 30 DEG C, hatch by lucifuge, the unnecessary DHR123 of M9 cleaning removing after 30min, the multi-functional microplate reader of upper SYNERGY2 detects fluorescence angle value (λ ex=485nm, λ em=520nm) change, the change of nematicide activity in vivo oxygen level is reflected with this.The results are shown in Figure 2.As shown in Figure 2, compared with matched group, 25 μMs of rotenone obviously can increase the level (P<0.001) of nematicide activity in vivo oxygen; And after giving 0.1mg/ml and 1mg/ml Carcinia mangostana L. shell extract intervention 24h, nematicide activity in vivo oxygen level is starkly lower than rotenone group (P<0.001, P<0.001).
Claims (10)
1. the application of Carcinia mangostana L. shell extract in the following product of preparation: 1) prevent and/or treat Parkinsonian product; 2) product of the degeneration of parkinson patient dopamine neuron dendron is prevented and/or treated; 3) anti-oxidation stress product; 4) product of parkinson disease oxidative stress is prevented and/or treated.
2. application according to claim 1, is characterized in that: described parkinson disease comprise Primary ventricular hemorrhage medicine and Secondary cases parkinson disease.
3. application according to claim 1 and 2, is characterized in that: described product is medicine and/or health product.
4. the application according to any one of claim 1-3, is characterized in that: described Carcinia mangostana L. shell extract is the ethanol water solution extract of Garcinia mangostana shell; The ethanol water of described ethanol water preferred volume mark 80 ~ 95%.
5. application according to claim 4, it is characterized in that: described Carcinia mangostana L. shell extract extracts by the following method and obtains: 80 ~ 95% ethanol waters that Garcinia mangostana shell volume fraction is are carried out reflux, extract, collect backflow and concentrate, by the concentrated solution vacuum drying obtained, obtain Carcinia mangostana L. shell extract;
Wherein, described reflux, extract, is at least carried out once, preferably extracts 2 times, and each time of extracting is 1-2 hour; During each extraction, the proportioning of Extraction solvent and described Garcinia mangostana shell is 8-10L:1kg.
6. a product, its active component is Carcinia mangostana L. shell extract;
Described product be selected from following any one: 1) prevent and/or treat Parkinsonian product; 2) product of the degeneration of parkinson patient dopamine neuron dendron is prevented and/or treated; 3) anti-oxidation stress product; 4) product of parkinson disease oxidative stress is prevented and/or treated.
7. product according to claim 6, is characterized in that: described parkinson disease comprise Primary ventricular hemorrhage medicine and Secondary cases parkinson disease.
8. the product according to claim 6 or 7, is characterized in that: described product is medicine and/or health product.
9. the product according to any one of claim 6-8, is characterized in that: described Carcinia mangostana L. shell extract is the ethanol water solution extract of Garcinia mangostana shell; The ethanol water of described ethanol water preferred volume mark 80 ~ 95%.
10. product according to claim 9, it is characterized in that: described Carcinia mangostana L. shell extract extracts by the following method and obtains: 80 ~ 95% ethanol waters that Garcinia mangostana shell volume fraction is are carried out reflux, extract, collect backflow and concentrate, by the concentrated solution vacuum drying obtained, obtain Carcinia mangostana L. shell extract;
Wherein, described reflux, extract, is at least carried out once, preferably extracts 2 times, and each time of extracting is 1-2 hour; During each extraction, the proportioning of Extraction solvent and described Garcinia mangostana shell is 8-10L:1kg.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009093255A2 (en) * | 2008-01-21 | 2009-07-30 | Ganga Raju Gokaraju | A new nutraceutical composition from garcinia mangostana |
| CN103211850A (en) * | 2013-04-23 | 2013-07-24 | 吉林化工学院 | Method for extracting flavone from mangosteen skin |
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- 2013-09-25 CN CN201310447244.XA patent/CN104435019A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009093255A2 (en) * | 2008-01-21 | 2009-07-30 | Ganga Raju Gokaraju | A new nutraceutical composition from garcinia mangostana |
| CN103211850A (en) * | 2013-04-23 | 2013-07-24 | 吉林化工学院 | Method for extracting flavone from mangosteen skin |
Non-Patent Citations (2)
| Title |
|---|
| J.PEDRAZA-CHAVERRÍ ET AL.: "ROS scavenging capacity and neuroprotective effect of α-mangostin against 3-nitropropionic acid in cerebellar granule neurons", 《EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY》 * |
| 龙云飞等: "山竹果皮提取物抗氧化活性的研究", 《食品工业科技》 * |
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Application publication date: 20150325 |