CN109692190A - Marchantia alcohol extract is in the application for preparing medicines resistant to liver cancer - Google Patents
Marchantia alcohol extract is in the application for preparing medicines resistant to liver cancer Download PDFInfo
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- CN109692190A CN109692190A CN201910080344.0A CN201910080344A CN109692190A CN 109692190 A CN109692190 A CN 109692190A CN 201910080344 A CN201910080344 A CN 201910080344A CN 109692190 A CN109692190 A CN 109692190A
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- marchantia
- liver cancer
- alcohol extract
- mpee
- cell
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Classifications
-
- 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
- A61K36/10—Bryophyta (mosses)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
-
- 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Alternative & Traditional Medicine (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention is marchantia alcohol extract in the application for preparing medicines resistant to liver cancer.The method that marchantia alcohol extract of the present invention inhibits liver cancer cell growth, inhibits fucosylation, inhibits H22 liver cancer mouse tumour growth, improves H22 liver cancer mouse survival rate in the application for preparing medicines resistant to liver cancer, marchantia alcohol extract.Marchantia alcohol extract is obtained using the method that dehydrated alcohol extracts, human liver cancer cell BEL-7404, HepG2 and murine hepatocarcinoma cell H22 are acted in vitro, confirm that MPEE can inhibit the growth of these three liver cancer cells, apoptosis, necrosis and the cell-cycle arrest for inducing liver cancer cells, inhibit the migration of liver cancer cells；Internal injection inhibits tumour growth to H22 liver cancer mouse, improves the survival rate of H22 liver cancer mouse, it was demonstrated that marchantia alcohol extract can be used as ideal anti-liver cancer and anti-drug candidate.
Description
Technical field
The invention belongs to the applications of marchantia alcohol extract, and in particular to marchantia alcohol extract is in the application for preparing medicines resistant to liver cancer.
Background technique
According to global cancer data statistics in 2017, liver cancer (Liver cancer) was incidence the 6th in world wide, extremely
Die the cancer of rate the 4th.China is Liver Cancer disease area, and liver cancer is in the third-largest main cause that China is cancer mortality.World wide
It is inside more than that 90% primary carcinoma of liver belongs to hepatocellular carcinoma (hepatocellular carcinoma).Currently, hepatectomy is liver
The primary treatment regimen of cell cancer, however, the patients with hepatocellular carcinoma only less than 30% meets hepatectomy standard, and due to multiple
Hair rate is high, and survival rate only has 35-50% within 5 years.It is very limited for mid-term and the available treatment method of advanced hepatocellular carcinoma patient.
Sorafenib (sorafenib) is a kind of molecular targeted agents, is ratified to use by U.S. Food and Drug Administration (FDA)
In the first-line treatment drug of advanced hepatocellular carcinoma, but Sorafenib can only extend patient 3 months life cycles, and reactivity is not
To 4%.Therefore, there is an urgent need to develop novel medicines resistant to liver cancer.
In recent years, more and more cancer patients select using supplement and alternative medicine (complementary and
Alternative medicine), traditional Chinese medicine is exactly the main source of supplement and alternative medicine, has there is application in thousands of years
History is the resources bank for screening safe and efficient anticancer drug.Traditional Chinese medicine is independent or combines with other strategies in clinic
On for treating hepatocellular carcinoma, and show clinical therapeutic efficacy, including extend life cycle, improve the quality of living, reduce secondary
Effect etc..
Bryophyte is between algae and vascular plant, as from aquatic to a kind of higher plant of terrestrial transition,
Various in style, chemical structure multiplicity, is potential natural active product treasure-house.Terpenoid, phenol in its secondary metabolites
Class compound and double Bibenzyl compounds etc. are the effective component of medicinal bryophytes, and pharmacological activity includes cell toxicant, antibacterial
Etc. a variety of effects.Marchantia is marchantia, and with all herbal medicine, the chemical component of marchantia mainly includes terpenoid, bibenzyl
Class compound etc..Some researches show that the marchantin A separated from marchantia, marchantia element B etc. to show antibacterial activity.
Marchantia of the present invention to be distributed in Xinjiang prepares marchantia alcohol extract (MPEE), passes through external people as experimental material
Source (BEL-7404, HepG2) and source of mouse (H22) hepatoma model detection MPEE make the inhibition of liver cancer cell growth and migration
With by H22 mouse tumor model detection MPEE in vivo to the inhibiting effect of tumour growth, while detection is raw to mice with tumor
The influence of rate is deposited, is laid the foundation for the research and development of novel medicines resistant to liver cancer.
Summary of the invention
The purpose of the present invention is to provide the new applications of marchantia extract, i.e., in the application for preparing medicines resistant to liver cancer, marchantia
Extract confirms that it can inhibit liver cancer cell growth and migration, pass through tumour by external source of people and source of mouse hepatoma model
Animal model proves that it can inhibit the growth of animal tumor and improve the survival rate of animal model for tumour.
To achieve the goals above, used technical solution are as follows:
Marchantia alcohol extract is in the application for preparing medicines resistant to liver cancer.
Further, active constituent is polyoses extract and chromocor extract in the marchantia alcohol extract.
Further, polyoses content is 42.5% in the marchantia alcohol extract, flavones content 5.6%.
Further, the marchantia alcohol extract inhibits the application of the drug of liver cancer cell growth in preparation.
Further, the marchantia alcohol extract inhibits the application of the drug of fucosylation in preparation.
Further, the marchantia alcohol extract inhibits the application of the drug of tumour growth in preparation.
Further, the marchantia alcohol extract improves the application of liver cancer mouse survival rate drug in preparation.
Further, the marchantia alcohol extract preparation method the following steps are included:
It after dry marchantia is crushed, is mixed with dehydrated alcohol according to the mass volume ratio of 1g:20ml, water-bath reflux mentions
It takes, then is centrifuged, take supernatant；
It refluxing extraction 3 times and is centrifuged again, merges supernatant, be concentrated after filtering, be dry, obtaining marchantia alcohol extract.
Further, the temperature of the water-bath refluxing extraction is 60 DEG C, time 2h；
The revolving speed of the centrifugation is 8000rpm, time 20min.
Further, the concentration uses concentrated by rotary evaporation, is concentrated into no ethanol flavor.
Compared with prior art, the beneficial effects of the present invention are:
For marchantia alcohol extract of the present invention in the application for preparing medicines resistant to liver cancer, marchantia alcohol extract inhibits liver cancer cells raw
Method that is long, inhibiting fucosylation, inhibit H22 liver cancer mouse tumour growth, improve H22 liver cancer mouse survival rate.It utilizes
The method that dehydrated alcohol extracts obtains marchantia alcohol extract, acts on human liver cancer cell BEL-7404, HepG2 and mouse in vitro
Liver cancer cells H22, it was demonstrated that MPEE can inhibit the growth of these three liver cancer cells, induce apoptosis, necrosis and the cell of liver cancer cells
Cycle Arrest inhibits the migration of liver cancer cells；Internal injection inhibits tumour growth to H22 liver cancer mouse, improves H22 liver cancer
The survival rate of mouse, it was demonstrated that marchantia alcohol extract can be used as ideal anti-liver cancer and anti-drug candidate.
Detailed description of the invention
Fig. 1 is the influence diagram that MPEE of the present invention grows liver cancer cells (H22, BEL-7404 and HepG2)；
Fig. 2 is influence diagram of the MPEE of the present invention to the H22 cell cycle；
Fig. 3 is influence diagram of the MPEE of the present invention to liver cancer cells (H22, BEL-7404 and HepG2) apoptosis；
Fig. 4 is MPEE of the present invention to the influence diagram of H22 mitochondrial membrane potential in anoxic, and wherein A is MPEE to mitochondrial membrane electricity
The influence diagram of position；
Fig. 5 is influence diagram of the MPEE of the present invention to H22 Apoptosis；
Fig. 6 is influence diagram of the MPEE of the present invention to external H22 cell migration；
Fig. 7 is influence diagram of the MPEE of the present invention to internal H22 tumour growth；
Fig. 8 is MPEE pairs of the present inventionThe influence diagram of mouse spleen index and spleen cell；
Specific embodiment
In order to which the present invention is further explained marchantia alcohol extract is in the application for preparing medicines resistant to liver cancer, reach expected invention mesh
, in conjunction with the preferred embodiment, to marchantia alcohol extract proposed according to the present invention in the application for preparing medicines resistant to liver cancer, tool
Body embodiment, structure, feature and its effect, detailed description is as follows.In the following description, different " embodiment " or " real
Apply example " refer to be not necessarily the same embodiment.In addition, the special characteristic, structure or feature in one or more embodiments can be by appointing
What suitable form combination.
Marchantia alcohol extract of the present invention is being elaborated before preparing the application of medicines resistant to liver cancer, it is necessary to in the present invention
The raw material referred to and method etc. are described further, to reach better effect.
Particular technique or condition are not specified in embodiment, according to the literature in the art described technology or conditions into
Row.Production firm person is not specified in raw materials used or equipment in embodiment, and being can be with conventional products that are commercially available.
Pharmaceutically acceptable carrier can be added marchantia alcohol extract of the invention when being prepared into pharmaceutical preparation, acceptable
Carrier is selected from the one or more of following carrier: preservative, surfactant, filler, wetting agent, dispersing agent, corrigent etc.,
Common carrier is such as: water, mannitol, dextran, sorbierite, mannitol, xylitol, sodium chloride, cellulose and cellulose
Derivative, sodium sulfite, alginates, gelatin, glycerol, Tween 80, agar, calcium carbonate, calcium bicarbonate, polyethylene glycol, β-ring paste
Essence, starch, Mint Essence, ethylparaben, sodium benzoate, sorbic acid etc..
The pharmaceutical preparation of marchantia alcohol extract of the invention, be by by marchantia raw material through extraction or other modes process,
Pharmaceutically active substance is made, then, pharmaceutically acceptable carrier is added using the active material as raw material, when needing, according to preparation
Pharmaceutical preparation is made in routine techniques.
The detailed description of Figure of description in the embodiment of the present invention are as follows:
Fig. 1 is the influence diagram that MPEE of the present invention grows liver cancer cells (H22, BEL-7404 and HepG2), and MPEE locates in vitro
Reason liver cancer cells 24 hours and 48 hours, wherein A is influence diagram of the MPEE to H22 cytomorphology, and B is MPEE to H22 cell
Active influence diagram, C are influence diagram of the MPEE to BEL-7404 and HepG2 cell activity, and D is MPEE living to Mouse spleen cells
The influence diagram of property.
Fig. 2 is MPEE of the present invention to the influence diagram of H22 cell cycle, and wherein A is influence of the MPEE to the H22 cell cycle
Figure, B are the influence diagram that MPEE expresses H22 Cell cycle-related genes, and C is that MPEE expresses H22 cell cycle related proteins
Influence diagram.
Fig. 3 is MPEE of the present invention to the influence diagram of liver cancer cells (H22, BEL-7404 and HepG2) apoptosis, and wherein A is
MPEE is to the influence diagram of H22 Apoptosis, and B is influence diagram of the MPEE to BEL-7404 Apoptosis, and C is that MPEE is thin to HepG2
The influence diagram of born of the same parents' apoptosis, D are influence diagram of the MPEE to normal liver cell NCTC apoptosis.
Fig. 4 is MPEE of the present invention to the influence diagram of H22 mitochondrial membrane potential in anoxic, and wherein A is MPEE to mitochondrial membrane electricity
The influence diagram of position, B are influence diagram of the MPEE to apoptosis-related protein (Bax, Bcl-2) and cytochrome c mRNA level in-site, and C is
For MPEE to the influence diagram of apoptosis-related protein (Bax, Bcl-2) and cytochrome c protein level, D is MPEE to H22 Apoptosis
The influence diagram of approach.
Fig. 5 is influence diagram of the MPEE of the present invention to H22 Apoptosis, and A is to locate in advance in caspase inhibitor Z-VAD-FMK
MPEE is to the influence diagram of H22 Apoptosis after reason, B be after 3 inhibitor Z-VAD-CHO of caspase pretreatment MPEE to H22
The influence diagram of Apoptosis.
Fig. 6 is influence diagram of the MPEE of the present invention to external H22 cell migration.
Fig. 7 is MPEE of the present invention to the influence diagram of internal H22 tumour growth, and wherein A is MPEE to mouse weight and tumour
The influence diagram of growth, B are influence diagram of the MPEE to mice with tumor survival rate.
Fig. 8 is MPEE pairs of the present inventionThe influence diagram of mouse spleen index and spleen cell, wherein A is MPEE pairsThe influence diagram of mouse spleen index and splenic cell number, B are MPEE pairsThe shadow of Mouse spleen cells subgroup
Ring figure.
After having understood above-mentioned raw materials and method etc., exist below in conjunction with specific embodiment to marchantia alcohol extract of the present invention
The application for preparing medicines resistant to liver cancer is further described in detail:
Embodiment 1.
The operating procedure for preparing marchantia alcohol extract is as follows:
Marchantia is collected in the Xinjiang forest farm Mu Lei and the sub- forest farm of Nanshan Mountain in Urumqi small ditch, takes dry marchantia plant, crushes
Powder is obtained, according to marchantia: the mixing of dehydrated alcohol=1g:20ml mass volume ratio, in 60 DEG C of water-bath refluxing extraction 2h, then
At 8000rpm, it is centrifuged 20min, takes supernatant.
Refluxing extraction 3 times again, and be centrifuged, merging supernatant, filtering back spin inspissation is reduced to no ethanol flavor, and it is dry, obtain marchantia
Alcohol extract (abbreviation MPEE) is sealed spare.
MPEE is dissolved with dimethyl sulfoxide (DMSO), polyoses content is measured using Anthrone-sulfuricacid method, polyoses content is
42.5%；Flavones content, flavones content 5.6% are measured using basic process.
Embodiment 2.
Prepare medicines resistant to liver cancer:
The marchantia alcohol extract 100mg for weighing above-mentioned preparation, is added in the water of 1000ml, after heating for dissolving, is fitted into close in bottle
Envelope, disinfection, is made the medicines resistant to liver cancer of 0.1mg/ml.
The marchantia alcohol extract 200mg for weighing above-mentioned preparation, is added in the water of 1000ml, after heating for dissolving, is fitted into close in bottle
Envelope, disinfection, is made the medicines resistant to liver cancer of 0.2mg/ml.
The marchantia alcohol extract 300mg for weighing above-mentioned preparation, is added in the water of 1000ml, after heating for dissolving, is fitted into close in bottle
Envelope, disinfection, is made the medicines resistant to liver cancer of 0.3mg/ml.
Embodiment 3.
The marchantia alcohol extract of preparation inhibits the screening of liver cancer cell growth in vitro:
Screening technique: by liver cancer cells culture to logarithmic growth phase, with various concentration MPEE (25,50,75,100 μ g/ml)
H22 cell is handled in vitro.MPEE is handled after different time (24,48 hours), observes H22 cellular morphology under the microscope,
MPEE in dosage and time dependence change H22 cell in the form of, cell, which becomes smaller, to be rounded, and cell quantity reduces (Figure 1A).
Using the proliferation activity of mtt assay detection H22 cell.As a result, it has been found that MPEE significantly suppress H22 cell proliferation activity (p <
0.001) dosage and time dependence are presented, and, MPEE 24 hours and 48 hours IC50 values be respectively 53.5 μ g/ml and
30.8 μ g/ml (Figure 1B).Find simultaneously, MPEE can also significantly inhibit BEL-7404 and HepG2 cell proliferation activity (p <
0.001), and dose dependent is presented, MPEE is respectively 108.4 μ g/ml and 118.4 μ g/ml (figure in 24 hours IC50 values
1C)。
We also have detected MPEE in vitro to the active influence of mouse spleen lymphocyte, with various concentration (25,50,75,
100 μ g/ml) MPEE processing fromThe isolated spleen cell of C57BL/6 mouse.After 24 hours and 48 hours, use
The activity of mtt assay detection Mouse spleen cells.The results show that MPEE is to spleen cell without toxic effect (Fig. 1 D).These
The result shows that growth of the MPEE in dose-dependently inhibition H22, BEL-7404 and HepG2 liver cancer cells, and to mice spleen
Dirty cytotoxic effect.
In order to prove that MPEE inhibits the mechanism of liver cancer cell growth, MPEE is further had detected to hepatoma cell apoptosis, bad
Extremely, the influence of cell cycle etc..H22 cell, after 24 hours, H22 are handled using the MPEE of various concentration (25,50,75 μ g/ml)
Cell is analyzed after PI is dyed with flow cytometer.As shown in Figure 2 A, 25 μ g/ml MPEE significantly increase G0/G1 cell
Ratio (p < 0.001), 50 and 75 μ g/ml MPEE significantly increase G2/M phase cell ratio (p < 0.001) and the sub-G1 phase it is thin
The ratio (p < 0.01) of born of the same parents.QRT-PCR result, which demonstrates high dose MPEE (75 μ g/ml), significantly reduces G0/G1 phase related gene
The mRNA level in-site (p < 0.001) of (Cyclin D1, CDK2) and G2/M phase related gene (Cyclin B, CDK1), significantly improve
The mRNA level in-site (p < 0.0001) (Fig. 2 B) of Gadd45 (retarded growth and DNA damage expression profile 45).Western
Blot result, which demonstrates MPEE, reduces the protein level of Cyclin D1, Cyclin B, CDK2, and dose dependent is presented
(Fig. 2 C).These results explanation, low dosage MPEE is by H22 cell-cycle arrest in the G0/G1 phase, and the MPEE of high dose is by H22
Cell-cycle arrest is in the G2/M phase.
H22 cell is handled using the MPEE of various concentration (25,50,75 μ g/ml), after 24 hours, with PI and Annexin V
Sample is analyzed to H22 cell dyeing and using flow cytometer.As shown in Figure 3A, MPEE is significantly induction of H22 cell
Apoptosis and necrosis (p < 0.001), but mainly induction of the apoptosis of cell.It finds simultaneously, MPEE is significantly induction of BEL-7404
And apoptosis and the necrosis (Fig. 3 B&C) of HepG2 cell.But MPEE is not significant to the apoptosis of normal liver cell NCTC and necrosis
It influences (Fig. 3 D).These are the results show that MPEE induces apoptosis and the necrosis of liver cancer cells, but will not induce normal liver cell
Apoptosis and necrosis.
The reduction of mitochondrial membrane potential (Δ ψ M) induces cell apoptosis.When Δ ψ m reduction, JC-1 polymer (red fluorescence)
Monomer (green fluorescence) can be resolved into.In order to prove whether the Apoptosis of MPEE induction is to be drawn by the reduction of mitochondrial membrane potential
It rises, is dyed, led to JC-1 after 24 hours using the MPEE processing H22 cell of various concentration (25,50,75 μ g/ml)
The detection of overflow-type cell instrument.As shown in Figure 4 A, MPEE significantly increases green fluorescence intensity (p < 0.0001), illustrates that MPEE is significant
Reduce Δ ψ M.- 2 protein family of B cell lymphoma/leukaemia includes that suppression apoptogene Bcl-2 and rush apoptogene Bax join
With the integrality of regulation mitochondrial membrane, Δ ψ m reduction causes cromoci (cytochrome C) to discharge, induces cell apoptosis.
After MPEE is handled H22 cell 24 hours, lytic cell extracts RNA and total protein, is examined respectively with qRT-PCR and Western blot
The variation of Bcl-2, the mRNA level in-site of Bax, cytochrome C and protein level are surveyed.The results show that MPEE improve Bax,
The mRNA and protein level of cytochrome C reduces the mRNA and protein level (Fig. 4 B&C) of Bcl-2.It finds simultaneously,
MPEE has activated caspase-3, caspase-8 and caspase-9 and promotes the shearing (Fig. 4 D) of PARP.As a result illustrate
MPEE is by mitochondria pathway induction of hepatoma cell apoptosis.It is further right by caspase broad spectrum inhibitors (Z-VAD-FMK)
H22 cell is pre-processed, the apoptosis (Fig. 5 A) for the H22 cell that discovery Z-VAD-FMK can partially reverse MPEE to induce；
3 inhibitor of Caspase (Z-VAD-CHO) pretreatment has obtained similar result (Fig. 5 B).These results suggest that MPEE passes through
Mitochondria pathway has activated caspase signal path, induction of hepatoma cell apoptosis.
Embodiment 4.
The marchantia alcohol extract of preparation inhibits the screening of fucosylation in vitro:
Metastases are the marks of tumor progression, in order to detect whether MPEE influences the migration of liver cancer cells, in vitro culture
H22 cell carries out scratching to cell when cell reaches 80% coverage, using various concentration (25,50,75 μ g/ml)
MPEE handles H22 cell, 24 hours and 48 hours after processing, is taken pictures using inverted microscope to scratch cell, Image J
Software analyzes scratch width.The results show that MPEE significantly inhibits cell migration (p < 0.0001), and present dosage according to
Rely property (Fig. 6).
Embodiment 5.
Inhibit the screening of liver cancer cell growth in the marchantia alcohol extract body of preparation:
In order to assess MPEE in vivo to the inhibiting effect of liver cancer cell growth, H22 tumor mouse model is established.By H22
Back on the right side of cell subcutaneous injection to Kunming white male mice, after 6 days, the mouse with tumour is grouped at random, and every group 8,
It is treated using intraperitoneal injection 50mg/kg (mouse weight) or 100mg/kg (mouse weight) MPEE, every other day injects one
It is secondary, amount to injection 10 times, DMSO (dimethyl sulfoxide, MPEE solvent) and Cisplatin (cis-platinum) are respectively as negative control group
And positive control.50mg/kg and 100mg/kg MPEE treatment group significantly suppresses mice tumors grew (p < 0.0001), and
And (Fig. 7 A) is not made significant difference to mouse weight.Although plus cisplatin in treatment group can also significantly inhibit tumour growth, alleviate small
Mouse weight has side effect to mouse.When tumor model group and all dead negative control group mouse as experimental endpoints
(after H22 cell infusion 56 days) count mice with tumor survival rate.The results show that 50mg/kgMPEE treatment group tumors mouse survival
Rate is 75% (2 death in 8 mouse)；100mg/kg MPEE treatment group tumors mouse survival rate is 87.5% (8 mouse
In 1 death), plus cisplatin in treatment group mice with tumor survival rate be 100% (Fig. 7 B).Mouse tumor model the result shows that, MPEE energy
Enough inhibit tumor growth in vivo and improves the survival rate of mice with tumor.
Embodiment 6.
The screening of the marchantia alcohol extract vivo immunization adjustment effect of preparation:
In order to assess the immunoregulation effect of MPEE, MPEE is by way of intraperitoneal injection or stomach-filling pairKunming white
Mouse is administered, and detects MPEE pairsThe influence of the ratio and quantity of immunocyte in mouse spleen index and spleen.Kun ming white mouse is randomly divided into 6 groups, and 50mg/kg (mouse weight), 100mg/kg (mouse weight) MPEE is injected intraperitoneally,
DMSO (dimethyl sulfoxide, MPEE is injected intraperitoneally in gastric infusion 50mg/kg (mouse weight), 100mg/kg (mouse weight) MPEE
Solvent) and non-administered group is as a control group.As a result, it has been found that compared with the control group, MPEE dramatically increases mouse spleen index and spleen
Dirty cell quantity (p < 0.05) (Fig. 8 A).Take spleen cell, the dyeing of streaming antibody, flow cytometry analysis sample.Such as Fig. 8 B institute
Show, 100mg/kgMPEE intraperitoneal injection group dramatically increases CD8 in mouse spleen+T cell, CD49+NK cell and CD11b+Macrophage is thin
The quantity (p < 0.05) of born of the same parents, 100mg/kgMPEE stomach-filling group dramatically increase CD8 in mouse spleen+T cell, CD49+The number of NK cell
It measures (p < 0.05).The above result shows that MPEE can increase the quantity of mouse spleen index and immunocyte, exempt to improve mouse
Epidemic disease power enhances MPEE antitumor efficacy.
Marchantia alcohol extract is had detected to the inhibiting effect of liver cancer, including external and experiment in vivo using different methods above
Detailed verifying has been carried out, and has illustrated its mechanism of action.It was found that marchantia alcohol extract has good antihepatocarcinoma effect.
The above is only the preferred embodiment of the embodiment of the present invention, not makees any shape to the embodiment of the present invention
Limitation in formula, any simple modification to the above embodiments of technical spirit according to an embodiment of the present invention, equivalent variations
With modification, in the range of still falling within technical solution of the embodiment of the present invention.
Claims (10)
1. marchantia alcohol extract is in the application for preparing medicines resistant to liver cancer.
2. application according to claim 1, which is characterized in that active constituent is Polyose extraction in the marchantia alcohol extract
Object and chromocor extract.
3. application according to claim 2, which is characterized in that polyoses content is 42.5% in the marchantia alcohol extract,
Flavones content is 5.6%.
4. application according to claim 1, which is characterized in that the marchantia alcohol extract inhibits liver cancer cells raw in preparation
The application of long drug.
5. application according to claim 1, which is characterized in that the marchantia alcohol extract inhibits liver cancer cells to move in preparation
The application of the drug of shifting.
6. application according to claim 1, which is characterized in that the marchantia alcohol extract inhibits tumour growth in preparation
The application of drug.
7. application according to claim 1, which is characterized in that the marchantia alcohol extract improves liver cancer mouse life in preparation
Deposit the application of the drug of rate.
8. application according to claim 1, which is characterized in that the preparation method of the marchantia alcohol extract includes following step
It is rapid:
After dry marchantia is crushed, mixed with dehydrated alcohol according to the mass volume ratio of 1g:20ml, water-bath refluxing extraction, then
Centrifugation, takes supernatant；
It refluxing extraction 3 times and is centrifuged again, merges supernatant, be concentrated after filtering, be dry, obtaining marchantia alcohol extract.
9. application according to claim 8, which is characterized in that the temperature of the water-bath refluxing extraction is 60 DEG C, the time
For 2h；
The revolving speed of the centrifugation is 8000rpm, time 20min.
10. application according to claim 8, which is characterized in that the concentration uses concentrated by rotary evaporation, is concentrated into no ethyl alcohol
Taste.
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| CN112156117A (en) * | 2020-09-21 | 2021-01-01 | 新疆前进荣耀投资有限公司 | Physcomitrella patens alcohol extract, preparation method thereof and application of physcomitrella patens alcohol extract in preparation of anti-liver cancer drugs |
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| CN101185661A (en) * | 2006-03-10 | 2008-05-28 | 徐�明 | Technique for preparing liverwort extract and application of it in preparing medicine for treating liver cancer and hepatitis B |
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| CN112156117A (en) * | 2020-09-21 | 2021-01-01 | 新疆前进荣耀投资有限公司 | Physcomitrella patens alcohol extract, preparation method thereof and application of physcomitrella patens alcohol extract in preparation of anti-liver cancer drugs |
| CN112156117B (en) * | 2020-09-21 | 2021-11-30 | 新疆前进荣耀投资有限公司 | Physcomitrella patens alcohol extract, preparation method thereof and application of physcomitrella patens alcohol extract in preparation of anti-liver cancer drugs |
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