CN113373098B - Stenotrophomonas H2 strain for treating Alzheimer disease and application thereof - Google Patents
Stenotrophomonas H2 strain for treating Alzheimer disease and application thereof Download PDFInfo
- Publication number
- CN113373098B CN113373098B CN202110854391.3A CN202110854391A CN113373098B CN 113373098 B CN113373098 B CN 113373098B CN 202110854391 A CN202110854391 A CN 202110854391A CN 113373098 B CN113373098 B CN 113373098B
- Authority
- CN
- China
- Prior art keywords
- strain
- stenotrophomonas
- huperzine
- alzheimer disease
- treating alzheimer
- 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.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/10—Nitrogen as only ring hetero atom
- C12P17/12—Nitrogen as only ring hetero atom containing a six-membered hetero ring
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention discloses an expression product stenotrophomonas H2 strain for treating Alzheimer disease and application thereof, wherein the strain is obtained by separating wild huperzia serrata endophytic bacteria, belongs to stenotrophomonas H2 strain, and has an amino sequence shown as SEQ ID NO: 1 is shown. The stenotrophomonas H2 strain is used as a biological strain for treating Alzheimer disease, the excellent huperzine A-producing high-efficiency expression gene of the stenotrophomonas H2 strain is transferred into other model strains, more excellent characters are obtained through gene modification, and in addition, the strain can be further optimized through mutation breeding. The research of the method has great significance for the industrialized production of huperzine A by biosynthesis, the protection of plant resources, the solution of the first-line clinical medication requirement and the reduction of the medical cost for treating the Alzheimer disease.
Description
Technical Field
The invention belongs to the technical field of microorganisms, and particularly relates to an expression product stenotrophomonas for treating Alzheimer disease, and an application of the bacterial strain.
Background
At present, acetylcholinesterase inhibitor drugs are in the leading position in the Alzheimer disease drug market. Huperzine A is a novel huperzine monomer alkaloid separated from folk herbal huperzia serrata, is a powerful reversible cholinesterase inhibitor, has a multi-target effect, has the inhibition effect on acetylcholinesterase 3 times that of physostigmine and 30 times that of galanthamine, has low peripheral adverse reaction, and is one of clinical preferable medicaments for treating Alzheimer disease.
The development history of the medicine derived from natural plants is long and the medicine is rich in vitality, the method for extracting and obtaining the huperzine A by the plants is the simplest and most convenient, but the bottleneck of lacking plant resources is faced by the method for extracting and obtaining the huperzine A by the plants; the chemical synthesis of huperzine A is still one of the important research and development ways, but the synthesis steps are complicated and expensive, and the pure optically active compound is difficult to obtain.
Therefore, the strain which is screened and separated from the wild huperzia serrata endophytic bacteria and has the huperzine A producing capability has great significance for treating the Alzheimer disease and protecting plant resources. Although huperzine A producing strains are developed and researched at home and abroad at present, Stenotrophomonas sp has few reports of huperzine A producing functions. The obtained Stenotrophomonas (Stenotrophoromonas sp) H2 strain can be transformed by biotechnology to provide new strain resources for the industrial production of huperzine A. Meanwhile, through the research on the mechanism of producing huperzine A by the strain, the huperzine A producing property and capability which are more excellent and stable are obtained by utilizing the synthetic biology.
Disclosure of Invention
The invention aims to provide an stenotrophomonas H2 strain for treating Alzheimer disease, and solves the bottleneck of plant resource shortage in the process of extracting huperzine A from plants; and the problems that the chemical synthesis steps are complicated, the cost is high, and the pure optically active compound is difficult to obtain.
Another purpose of the invention is to provide stenotrophomonas H2 strain which can be used for treating Alzheimer disease, and the application of the stenotrophomonas H2 strain as a functional strain for treating Alzheimer disease in the aspect of biosynthesis pharmacy.
The first technical scheme adopted by the invention is as follows: stenotrophomonas H2 strain for treating Alzheimer disease, the strain is preserved in China general microbiological culture Collection center with the preservation number: CGMCC No.21400, preservation date: 12/18/2020.
The first technical solution adopted by the present invention is further characterized in that,
the strain is separated from wild Huperzia serrata (Huperzia serrata) endophytic bacteria, belongs to Stenotrophomonas sp strain H2, and has an amino acid sequence shown in SEQ ID NO: 1 is shown.
The culture conditions for the efficient expression of the huperzine A by the bacterial strains are as follows:
(1) culture medium: 300g of potatoes, 20g of glucose and 1000mL of distilled water;
(2) the culture conditions are as follows: at 25 ℃, 220 r/min;
(3) liquid loading amount: a 250mL conical flask, the liquid loading capacity is 100 mL;
(4) culturing time: and 2 days.
Laboratory storage conditions for the strains were: (1) after the strain is subcultured on a solid inclined plane of a culture medium every time, the growth time is 24 hours; (2) the strain preservation condition is 4 ℃, and after 12 hours, the strain is placed in a refrigerator with the temperature of 25 ℃ below zero for preservation.
The second technical scheme adopted by the invention is as follows: use of strain Stenotrophomonas H2 isolated from endophytic bacteria of wild Huperzia serrata (Huperzia serrata) belonging to the genus Stenotrophomonas H2, for the biosynthetic pharmaceutical use of strains of Stenotrophomonas H2 useful for the treatment of Alzheimer's disease, said strains having the accession number: CGMCC No. 21400.
The third technical scheme adopted by the invention is as follows: the stenotrophomonas H2 strain can be used for treating Alzheimer disease, and bacterial strains are genetically modified through transgenosis and mutation breeding to obtain a series of strains with higher expression efficiency and better genetic stability, but the technical means of the genetic modification is not limited to the above, and other biological technologies can also be adopted for the application of the genetic modification.
The invention has the beneficial effects that the stenotrophomonas H2 strain for treating the Alzheimer disease can be used as a biological strain for treating the Alzheimer disease, the excellent huperzine A-producing high-efficiency expression gene of the stenotrophomonas H2 strain is transferred into other model strains, more excellent characters are obtained through gene modification, and in addition, the strain can be further optimized through mutation breeding. The research of the method has great significance for the industrialized production of huperzine A by biosynthesis, the protection of plant resources, the solution of the first-line clinical medication requirement and the reduction of the medical cost for treating the Alzheimer disease.
Drawings
FIG. 1 is a high performance liquid chromatography detection chart of the huperzine A producing ability of the bacterial strain for efficiently expressing huperzine A;
FIG. 2 is a high performance liquid chromatography detection chart of huperzine A standard;
FIG. 3 is an electrophoresis diagram of a PCR product for detecting DNA extracted from the bacterial strain of the present invention by agarose gel electrophoresis;
FIG. 4 is the morphological diagram of the bacterial strain of the present invention for highly expressing huperzine A.
Detailed Description
The present invention will be described in detail below with reference to the accompanying drawings and specific embodiments.
The invention relates to a Stenotrophomonas H2 strain for treating Alzheimer disease and application thereof, wherein the strain is obtained by separating wild Huperzia serrata (Huperzia serrata, Huperzia) endophytic bacteria, belongs to Stenotrophomonas H2 strain, and has an amino sequence shown as SEQ ID NO: 1 is shown.
The strain is preserved in China general microbiological culture Collection center of the preservation unit appointed by the national intellectual property office.
Biological material preservation information:
name: stenotrophomonas (Stenotrophomonas sp.) strain H2
The preservation number is: CGMCC No.21400
The preservation unit: china general microbiological culture Collection center (CGMCC)
Preservation time: 12 and 18 months in 2020
Address: xilu No. 1 Hospital No. 3 of Beijing market facing Yang district
The separation method of the huperzine A strain for high-efficiency expression comprises the following steps:
washing fresh Huperzia serrata with tap water, sterilizing the surface of Huperzia serrata with 75% alcohol for 30s, washing with sterile water for 4 times, soaking with 10% NaClO for 5min, washing with sterile water for 4 times, sterilizing the surface with 75% ethanol for 30s, washing with sterile water for 4 times, cutting the stem into 0.5cm size with sterile blade, cutting the blade into 0.3cm × 0.3cm pieces, inoculating to solid culture medium containing streptomycin 15 μ g/mL and deoxycholate sodium 1mg/mL, and culturing at 25 deg.C in dark. To examine whether the surface was sterilized completely, sterile water was applied to the culture medium for the last time the tissue mass was washed during the sterilization process. 2d, picking hyphae growing on the stem section and the blade cut by an aseptic operation method, transferring the hyphae to a fresh culture medium plate by a plate streaking method, and repeating the operation until purified endophytes are obtained.
(II) preparing a fermentation liquor of the high-efficiency expression huperzine A strain: the purified endophytes obtained by separation are respectively inoculated into 250mL conical flasks (each strain is inoculated into 3 flasks) filled with 100mL liquid culture medium, and the flasks are placed on a shaker for shaking culture at 25 ℃ and 220r/min for 2 d. 3 replicates were set. After the endophytic bacteria are cultured for 2d by shaking, the fermentation liquor is centrifuged for 15min at 10000 r/min.
(III) analyzing and determining the products of the high-efficiency expression huperzine A strain: taking 500mL of supernatant after the fermentation liquid is centrifuged, extracting huperzine A by adopting a dichloromethane and ether extraction method, dissolving with 0.01mol/L hydrochloric acid to a constant volume of 5mL, and measuring the content of the huperzine A produced by the fermented supernatant by using a high performance liquid chromatography. High Performance Liquid Chromatography (HPLC) column is Agilent Cl8 column (4.60mm × 250mm, 5 μm); the chromatographic conditions are as follows: the mobile phase is phosphate buffer-acetonitrile (86: 14); the flow rate is 1.0 mL/min; the column temperature is 25 ℃, and the sample injection amount is 20 mu L; the detection wavelength is 310 nm. Huperzine A standard was used as a control.
Precisely weighing huperzine A standard substance, dissolving with 0.01mol/L hydrochloric acid solution, sequentially preparing into 2, 0.2, 0.02, 0.002, 0.0002mg/mL mass concentrations, and injecting sample of 20 μ L respectively. Each time 5 replicates to ensure good precision. And (4) drawing a standard curve by using the peak area and the quality of the corresponding huperzine A standard substance to obtain a linear regression equation. Calculating and separating by linear regression equation to obtain metabolite content of the huperzine A producing strain. The results are shown in fig. 1 and fig. 2, the results in fig. 1 show that 6.984min is observed when the huperzine A standard substance peaks, the results in fig. 2 show that 6.778min is observed when the fermentation broth extract of strain H2 shows that the peak time of the two is close, and the peak time of HPLC is overlapped when the standard substance is added into the fermentation broth extract of strain H2, and the results show that huperzine A exists in the fermentation broth extract of strain H2.
(IV) identifying the molecular biology of the high-efficiency expression huperzine A strain:
1. genomic DNA extraction
1) And (3) taking 1.5mL of a centrifuge tube, adding 200 mu L of pretreatment solution and three glass beads, then adding an appropriate amount of bacteria sample, and putting the bacteria sample into a grinding instrument to be ground fully.
2) Adding 20 mu L of protease K solution, mixing uniformly, and standing at 37 ℃ for 30-60 min.
3) Add 200. mu.L of lysis buffer, mix well by inversion, and stand at 70 ℃ for 10 min.
4) Add 200. mu.L of absolute ethanol, mix well by inversion, and centrifuge briefly to remove droplets on the inner wall of the tube cap.
5) Passing through adsorption column, washing with washing solution for 1 time, and washing with rinsing solution for 2 times.
6) And (5) placing the adsorption column at room temperature for 5-10 minutes to thoroughly dry the residual rinsing liquid in the adsorption material.
7) Transferring the adsorption into a new centrifuge tube, suspending and dropwise adding 50-100 mu LddH2O to the middle position of the adsorption film, standing at room temperature for 5-10 min, centrifuging at 12000rpm for 2min, and collecting the solution into the centrifuge tube.
2.16S amplification
1) The primer sequence is as follows:
27F：5’-AGAGTTTGATCCTGGCTCAG-3’；
1492R：5’-TACGGCTACCTTGTTACGACTT-3’；
2) PCR reaction system
3) PCR cycling conditions
PCR product detection and purification
The PCR product of 3 mul is detected by 1.0 percent agarose gel, and Marker bands are 5000bp, 3000bp, 2000bp, 1000bp, 750bp, 500bp, 250bp and 100bp from top to bottom. The results of electrophoretic PCR products are shown in FIG. 3. FIG. 3(a) is a strain detection region, FIG. 3(b) is a Marker control region, a 2000bp band concentration of 60ng/3ul is shown as a highlighted band, and the remaining band concentrations are all 30 ng/3. mu.L. As a result: the DNA amplification band of the H2 strain for the purpose of detection is about 1000-2000bp through agarose gel electrophoresis determination, and has no upper and lower hybrid bands.
And (3) purifying the PCR product according to the operation of a magnetic bead purification standard operation flow, adsorbing DNA in a high-salt low-pH solution by utilizing the principle that magnetic beads can adsorb or release substances with charges, and releasing DNA in a low-salt high-pH solution, so that the aim of separating and purifying the DNA product is fulfilled.
4. Sequencing
The PCR product was identified and sequenced by Beijing Liu-He-Hua Dagenescience and technology Limited.
According to blast results, strain H2 was most closely related to the parent Stenotrophoromonas sp.
The bacterial strain for efficiently expressing huperzine has the following characteristics:
1. morphological characteristics under mirror
FIG. 4 shows the bacterial strain form for the efficient expression of huperzine A in the present inventionState diagram, as shown in FIG. 4(a), the strain G-Bacilli, gram-stained red, are short or long rod-shaped, with rods of varying lengths.
2. Morphological characteristics of bacterial colony
As shown in FIG. 4(b), the bacterial strain has large colony on the solid medium, yellow to orange color, round shape, convex shape, opaque shape, neat edge and stickiness.
3. The culture conditions for the bacterial strain to efficiently express the huperzine A are as follows:
(1) culture medium: 300g of potatoes, 20g of glucose and 1000mL of distilled water.
(2) The culture conditions are as follows: at 25 ℃ and 220 r/min.
(3) Liquid loading amount: 250mL conical flask, the liquid loading is 100 mL.
(4) Culturing time: and 2 days.
The H2 strain is a bacterium belonging to Stenotrophomonas sp, and can obtain huperzine A with high yield by liquid fermentation culture and extraction of metabolites.
The results of comparison of 16S of the bacterial strains of the present invention with the same species of the same genus are as follows:
similarity to Stenotrophomonas sp.ass1 was 99.93%;
similarity to Stenotrophomonas maltophilia SJTL3 was 99.93%;
the similarity to Stenotrophoromonas maltophia ISMMS2 was 99.93%.
The genus has been reported to have the ability to produce huperzine A. Through the mechanism research, the research on the high-efficiency expression gene in the huperzine A produced by the strain can be further deepened, so that a new transgenic organism is constructed, and the high-efficiency expression is obtained. Stenotrophomonas (Stenotrophomonas sp) H2 strain is used as a new huperzine A producing strain, and provides a new strain resource for synthesizing huperzine A in a biosynthesis way.
SEQUENCE LISTING
<110> Xian medical college
<120> stenotrophomonas H2 strain for treating Alzheimer disease and application thereof
<130> 2021
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 1397
<212> DNA
<213> Stenotrophomonas (Stenotrophoromonas sp.)
<400> 1
ggctcagagt gaacgctggc ggtaggccta acacatgcaa gtcgaacggc agcacagagg 60
agcttgctcc ttgggtggcg agtggcggac gggtgaggaa tacatcggaa tctactctgt 120
cgtgggggat aacgtaggga aacttacgct aataccgcat acgacctacg ggtgaaagca 180
cgtgggggat aacgtaggga aacttacgct aataccgcat acgacctacg ggtgaaagca 240
cgtgggggat aacgtaggga aacttacgct aataccgcat acgacctacg ggtgaaagca 300
actgagacac ggtccagact cctacgggag gcagcagtgg ggaatattgg acaatgggcg 360
caagcctgat ccagccatac cgcgtgggtg aagaaggcct tcgggttgta aagccctttt 420
gttgggaaag aaatccagct ggctaatacc cggttgggat gacggtaccc aaagaataag 480
caccggctaa cttcgtgcca gcagccgcgg taatacgaag ggtgcaagcg ttactcggaa 540
ttactgggcg taaagcgtgc gtaggtggtc gtttaagtcc gttgtgaaag ccctgggctc 600
ttactgggcg taaagcgtgc gtaggtggtc gtttaagtcc gttgtgaaag ccctgggctc 660
tggtgtagca gtgaaatgcg tagagatcag gaggaacatc catggcgaag gcagctacct 720
ggaccaacac tgacactgag gcacgaaagc gtggggagca aacaggatta gataccctgg 780
tagtccacgc cctaaacgat gcgaactgga tgttgggtgc aatttggcac gcagtatcga 840
agctaacgcg ttaagttcgc cgcctgggga gtacggtcgc aagactgaaa ctcaaaggaa 900
ttgacggggg cccgcacaag cggtggagta tgtggtttaa ttcgatgcaa cgcgaagaac 960
cttacctggc cttgacatgt cgagaacttt ccagagatgg attggtgcct tcgggaactc 1020
gaacacaggt gctgcatggc tgtcgtcagc tcgtgtcgtg agatgttggg ttaagtcccg 1080
caacgagcgc aacccttgtc cttagttgcc agcacgtaat ggtgggaact ctaaggagac 1140
cgccggtgac aaaccggagg aaggtgggga tgacgtcaag tcatcatggc ccttacggcc 1200
agggctacac acgtactaca atggtaggga cagagggctg caagccggcg acggtaagcc 1260
aatcccagaa accctatctc agtccggatt ggagtctgca actcgactcc atgaagtcgg 1320
aatcgctagt aatcgcagat cagcattgct gcggtgaata cgttcccggg ccttgtacac 1380
accgcccgtc acaccat 1397
Claims (2)
1. Stenotrophomonas (A) for treating Alzheimer diseaseStenotrophomonas sp.) The H2 strain, which is characterized in that the strain is preserved in China general microbiological culture Collection center with the preservation number: CGMCC No. 21400.
2. Stenotrophomonas (A) for treating Alzheimer diseaseStenotrophomonas sp.) Application of H2 strain in biosynthesis of medicines as functional strain for treating Alzheimer disease, wherein strain is selected from wild huperzia serrata (Huperzia serrata) (A)Huperzia serrata) Separated from endophytic bacteria, belonging to stenotrophomonas (A)Stenotrophomonas sp.) H2 strain, the accession number of the bacterial strain: CGMCC No. 21400.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110854391.3A CN113373098B (en) | 2021-07-28 | 2021-07-28 | Stenotrophomonas H2 strain for treating Alzheimer disease and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110854391.3A CN113373098B (en) | 2021-07-28 | 2021-07-28 | Stenotrophomonas H2 strain for treating Alzheimer disease and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113373098A CN113373098A (en) | 2021-09-10 |
| CN113373098B true CN113373098B (en) | 2022-07-01 |
Family
ID=77582965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110854391.3A Active CN113373098B (en) | 2021-07-28 | 2021-07-28 | Stenotrophomonas H2 strain for treating Alzheimer disease and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113373098B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011065769A2 (en) * | 2009-11-25 | 2011-06-03 | Industry-Academy Cooperation Corps. Of Sunchon National University | Cell or culture extract of cladonia macilenta purple and/or biruloquinone as acetylcholinesterase inhibitors |
| CN105647819A (en) * | 2016-03-02 | 2016-06-08 | 西安医学院 | Fungus strain with Alzheimer's disease treating function and application of fungus strain |
| CN105670940A (en) * | 2016-03-02 | 2016-06-15 | 西安医学院 | Fungus strain with high-efficiency expression of huperzine A and application thereof |
| CN106497803A (en) * | 2016-12-26 | 2017-03-15 | 西安医学院 | A kind of reaping hook with product huperzine A function belongs to endogenetic fungus and its application |
| CN106497804A (en) * | 2016-12-26 | 2017-03-15 | 西安医学院 | A kind of tunning is applied to fungal bacterial strain and its application for treating dementia |
| CN107488619A (en) * | 2017-09-30 | 2017-12-19 | 中南民族大学 | The monad SXZ N10 bacterial strains and purposes of one plant of production huperzine and Huperzine B |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110243957A1 (en) * | 2008-09-24 | 2011-10-06 | University Of South Florida | Materials and methods for preventing or treating neurodegenerative conditions associated with abeta peptide accumulation |
-
2021
- 2021-07-28 CN CN202110854391.3A patent/CN113373098B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011065769A2 (en) * | 2009-11-25 | 2011-06-03 | Industry-Academy Cooperation Corps. Of Sunchon National University | Cell or culture extract of cladonia macilenta purple and/or biruloquinone as acetylcholinesterase inhibitors |
| CN105647819A (en) * | 2016-03-02 | 2016-06-08 | 西安医学院 | Fungus strain with Alzheimer's disease treating function and application of fungus strain |
| CN105670940A (en) * | 2016-03-02 | 2016-06-15 | 西安医学院 | Fungus strain with high-efficiency expression of huperzine A and application thereof |
| CN106497803A (en) * | 2016-12-26 | 2017-03-15 | 西安医学院 | A kind of reaping hook with product huperzine A function belongs to endogenetic fungus and its application |
| CN106497804A (en) * | 2016-12-26 | 2017-03-15 | 西安医学院 | A kind of tunning is applied to fungal bacterial strain and its application for treating dementia |
| CN107488619A (en) * | 2017-09-30 | 2017-12-19 | 中南民族大学 | The monad SXZ N10 bacterial strains and purposes of one plant of production huperzine and Huperzine B |
Non-Patent Citations (3)
| Title |
|---|
| Five novel and highly efficient endophytic fungi isolated from Huperzia serrata expressing huperzine A for the treatment of Alzheimer’s disease;Han Wen-Xia et al.;《Applied Microbiology and Biotechnology》;20200924;第104卷;第9159–9177页 * |
| 产石杉碱甲新资源研究方法探索;韩文霞等;《海南医学》;20150831;第26卷(第15期);第2275-2278页 * |
| 蛇足石杉中产石杉碱甲内生真菌的分离和鉴定;韩文霞等;《微生物学通报》;20170920;第44卷(第9期);第2153-2160页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113373098A (en) | 2021-09-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107338198A (en) | A kind of Lactobacillus plantarum and its application | |
| CN103555607B (en) | A kind of endophyte H6 strain separation methods in silk tree blade and its application | |
| CN105670940B (en) | A kind of fungal bacterial strain of high efficient expression huperzine and its application | |
| CN103911293B (en) | The endogenetic fungus that one plant height is paclitaxel produced and apply this bacterial strain and produce the method for taxol | |
| CN113430146B (en) | Bacillus thuringiensis HW1 strain for expressing huperzine A and application thereof | |
| CN106497803B (en) | Fusarium endophytic fungus with huperzine A production function and application thereof | |
| CN108410762A (en) | A kind of streptococcus novel species HTS20 and its application | |
| CN116350662A (en) | Microorganism strain of chaetoviridae, medicament for preventing or treating tumor and application thereof | |
| CN113373098B (en) | Stenotrophomonas H2 strain for treating Alzheimer disease and application thereof | |
| CN105647819B (en) | A kind of fungal bacterial strain and its application with treatment Alzheimer disease function | |
| CN102807955B (en) | Method for preparing anti-tumor compound Rasfonin and special strain of method | |
| CN108485999B (en) | A kind of streptococcus novel species HTS25 and its application | |
| CN113337449B (en) | Serratia marcescens HL1 strain for treating Alzheimer disease and application thereof | |
| CN106497804B (en) | Fungus strain with fermentation product applied to treatment of dementia and application of fungus strain | |
| CN113528391B (en) | Stenotrophomonas H1 strain for efficiently expressing huperzine A and application thereof | |
| CN111690551A (en) | Separation, purification, culture and identification method for brucella | |
| Majolagbe et al. | Synthesis of Endophytic Fungi Metabolites, Antimicrobial Potentials, and Detection of their Bioactive Molecules Using Gas Chromatography-Mass Spectrometry. | |
| CN105670941B (en) | A kind of fungal bacterial strain and its application with acetylcholine esterase inhibition function | |
| CN113637605B (en) | Bacillus amyloliquefaciens and application thereof in preparation of 1-deoxynojirimycin | |
| Arshad et al. | Characterization of Pseudomonas cichorii isolated from tomato and lettuce in Iran | |
| CN1369550A (en) | Culture medium of staphylococcus aureus and its preparing process | |
| CN108424866A (en) | A kind of sturgeon source Aeromonas media AMth-1 and PCR detection primer and application | |
| CN111117917B (en) | Primary tetraodotoxin-producing globefish co-habitat and application thereof | |
| CN114395509A (en) | Bacillus WYJ-E14 separated from Curcuma wenyujin and its application in preparing antineoplastic agent | |
| CN115093972B (en) | Cordyceps militaris strain and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |