CN116687910A - Tea composition capable of regulating estrogen signal pathway and application thereof in preventing and treating neurodegenerative diseases - Google Patents
Tea composition capable of regulating estrogen signal pathway and application thereof in preventing and treating neurodegenerative diseases Download PDFInfo
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- CN116687910A CN116687910A CN202210180591.XA CN202210180591A CN116687910A CN 116687910 A CN116687910 A CN 116687910A CN 202210180591 A CN202210180591 A CN 202210180591A CN 116687910 A CN116687910 A CN 116687910A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pharmacology & Pharmacy (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Tea composition capable of regulating estrogen signaling pathway and application thereof in preventing and treating neurodegenerative diseases, wherein the main active ingredient of the tea composition capable of regulating estrogen signaling pathway is theaflavin digallate (TFDG), and an effective amount of the tea composition can be used for up-regulating estrogen signaling pathway in PC12 cells. The effective amount is an amount of the tea composition effective to up-regulate the expression of at least one of cytokeratin gene Krt, keratin-related protein gene Krtap, and type II keratin gene by 40% or more. The tea composition capable of regulating the estrogen signal pathway can promote the axon growth of PC12 cells by up-regulating the expression of keratin genes in the estrogen signal pathway, thereby playing a role in protecting nerves. The application also provides application of the tea composition capable of regulating the estrogen signal path in preventing and treating neurodegenerative diseases.
Description
Technical Field
The application relates to the field of preventing and treating neurodegenerative diseases, in particular to a tea composition capable of regulating estrogen signal paths and application thereof in preventing and treating neurodegenerative diseases.
Background
Alzheimer's Disease (AD) is a neurodegenerative disease that clinically manifests as progressive cognitive decline, and in recent years, AD is the most common dementia disease worldwide. At present, the cause and pathogenesis of AD are not clear, and senile plaques consisting of beta-amyloid (aβ) and neurofibrillary tangles formed by tau protein phosphorylation, which appear in the brain of AD patients, become two typical pathological features in AD pathogenesis. There are numerous theories for explaining the pathogenesis of AD, such as amyloid deposition, apoptosis or loss of nerve cells, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, inflammation, etc., but the pathogenesis of AD has not been reported to be related to gene expression on the estrogen signaling pathway in terms of gene expression, and it has not been reported that neurodegenerative diseases such as AD can be prevented and treated by regulating the gene expression of the estrogen signaling pathway.
Theaflavins are benzoazepinone compounds generated after the catechin undergoes the enzymatic reaction to undergo the phenylpropyl cyclization, have remarkable cardiovascular protection effect and have the reputation of soft gold. Theaflavin digallate (TFDG) is one of the main monomer components of theaflavin TFs, contains more aromatic rings and hydroxyl groups than EGCG (figure 1), and has the effects of resisting oxidation, resisting inflammation, preventing and treating cardiovascular diseases, reducing blood fat, resisting cancer and preventing cancer, etc., but the prior art does not report that theaflavin is used as an estrogen signal regulator, plays a role in protecting nerve cells, promotes the axon growth of nerve cells, and is used for preventing and treating neurodegenerative diseases such as AD.
Disclosure of Invention
The application aims to solve the technical problems that: the tea composition which takes theaflavin as a main raw material and is used as an estrogen signal regulator and can regulate an estrogen signal path is provided to overcome the defects of the prior art, protect nerve cells, promote the axon growth of the nerve cells and the application of the tea composition in preventing and treating neurodegenerative diseases.
One of the technical schemes adopted for solving the technical problems is as follows:
a tea composition which modulates an estrogen signaling pathway, the major active ingredient of said tea composition being theaflavin digallate (TFDG), and an effective amount of the tea composition is capable of upregulating an estrogen signaling pathway in PC12 cells.
The effective amount is an amount effective to up-regulate the expression of at least one gene selected from the group consisting of a cytokeratin gene (keratins, abbreviated as Krt), a keratin-related protein gene (keratin-associated protein, abbreviated as Krtap), and a type II keratin, abbreviated as Kb by 40% or more.
The effective amount refers to the concentration of theaflavin digallate TFDG as the main active ingredient of the tea composition is more than or equal to 10 mu M (solvent type), or 10mg/g (tablet).
At least one Krt gene is selected from the group consisting of Krt1, krt5, krt14, krt15, krt16, krt17, krt25, krt27, krt28, krt31, krt32, krt34, krt35, krt73, krt75, krt81, krt83, krt86, and at least one Krtap gene is selected from the group consisting of Krtap7-1, krtap8-1, krtap11-1, type II keratin gene is Kb23.
The active ingredients of the tea composition comprise theaflavin digallic acid ester and derivatives thereof, and pharmaceutically acceptable salts, hydrates or any combination thereof.
The theaflavin digallate derivative comprises theaflavin TF1, theaflavin-3-gallate (TF-3G), theaflavin-3 '-gallate (TF-3' G), thearubigin, theabrownin and other water extracts of black tea.
The tea composition further comprises a pharmaceutically acceptable excipient or carrier.
The other technical scheme adopted by the application for solving the technical problems is as follows:
use of a tea composition capable of modulating estrogen signaling pathway for the prevention and treatment of neurodegenerative diseases.
The specific method of use comprises administering to the patient an effective amount of a tea composition, the effective amount being an amount effective to up-regulate the expression of at least one Krt gene or Krtap gene by at least 40% of the tea composition.
The tea composition can prevent or treat neurodegenerative diseases by up-regulating at least one Krt gene or Krtap gene expression by at least 40% or more and promoting neurite growth of nerve cells.
The tea composition can prevent or treat neurodegenerative diseases by up-regulating expression of two or more Krt genes or Krtap genes by at least 40% or more and promoting neurite growth of nerve cells.
The tea composition can prevent or treat neurodegenerative diseases by up-regulating 2 or more of Krt5, krt14, krt17, krt25, krt27, krt31 and Krt35 genes to express at least 40%.
The tea composition upregulates the estrogen signaling pathway in PC12 cells by binding to at least one estrogen receptor.
The tea composition capable of regulating the estrogen signal pathway has the beneficial effects that:
the tea composition stimulates the transcription level of protein family genes such as Krt14 and Krt15, so that the up-regulated expression of cytokeratin genes (keratins, abbreviated as Krt) or/and keratin related protein genes (keratin-associated protein, abbreviated as Krtap) has obvious regulation effect on the gene layer facing an estrogen signal pathway, and the up-regulated trend of the keratin family genes can protect PC12 cells from oxidative shock caused by glutathione consumption and increase NGF-induced axon generation, so that the estrogen signal pathway has important effects on protecting nerve cells and promoting the growth of nerve axons.
In PC12 cells, cytokeratin and neurofilament proteins are co-expressed, forming keratin intermediate filaments and neurofilaments. Keratin intermediate filaments are the third framework component of cells and are involved in important vital activity processes such as cell differentiation, intracellular information transmission, and the like. In addition, keratin can promote the extension of neuron axons, and can be used as a catheter filler for peripheral nerve regeneration.
Drawings
FIG. 1 is a schematic representation of the molecular formula of TFDG in a tea composition with modulated estrogen signaling pathway according to the present application;
FIG. 2-ELISA assay of the axon growth factor GAP43 of PC12 cells cultured with a tea composition for modulating estrogen signaling pathway of example 1;
FIG. 3-is a graph of intracellular energy-currency ATP levels analysis of PC12 cultured with a tea composition capable of modulating estrogen signaling pathway in example 1;
FIG. 4-an inverted microscopic view of the morphology of cells (bar=50 μm) of a tea composition of example 1 with modulated estrogen signaling pathway after treatment for PC cell culture;
FIG. 5-DAPI staining pattern (bar=50. Mu.m) of a tea composition of example 1 with an adjustable estrogen signaling pathway after treatment in PC cell culture;
FIG. 6-A tea composition for inhibiting Abeta, which is an estrogen-signaling pathway-regulated tea composition of example 1 25-35 Differential gene volcanic pattern of induced PC12 injury;
FIG. 7-A tea composition for inhibiting Abeta, which is an estrogen-signaling pathway-regulated tea composition of example 1 25-35 Differential gene PPI network map analysis of induced PC12 injury, red for up-regulation, green for down-regulation, and dot size for relative expression;
FIG. 8-A tea composition for inhibiting Abeta, which is an estrogen-signaling pathway-regulated tea composition of example 1 25-35 Differential gene GO enrichment analysis of induced PC12 injury;
FIG. 9-A tea composition for inhibiting Abeta, which is an estrogen-signaling pathway-regulated tea composition of example 1 25-35 Induced PC12 injuryDifferential gene KEGG enrichment analysis;
FIG. 10-A tea composition for inhibiting Abeta, which is an estrogen-signaling pathway-regulated tea composition of example 1 25-35 Estrogen signal pathway differential gene thermogram of induced PC12 lesions;
FIG. 11-A tea composition for inhibiting Abeta, which is an estrogen-signaling pathway-regulated tea composition of example 1 25-35 Estrogen signaling pathway aβ for induced PC12 damage 25-35 And Aβ 25-35 Analysis of relative expression level of mRNA in TFDG.
Detailed Description
The application is further described below with reference to the drawings and examples.
Example 1
A tea composition of this example having an estrogen signaling pathway modulating active ingredient which is theaflavin digallate (TFDG) at a concentration of 50 μm and an effective amount of the tea composition is capable of upregulating estrogen signaling pathway in PC12 cells.
The effective amount is an amount effective to up-regulate the expression of at least one gene of a cytokeratin gene (keratins, abbreviated as Krt), a keratin-related protein gene (keratin-associated protein, abbreviated as Krtap), and a type II keratin, abbreviated as Kb by more than 40%.
The Krt genes include Krt1, krt5, krt14, krt15, krt16, krt17, krt25, krt27, krt28, krt31, krt32, krt34, krt35, krt73, krt75, krt81, krt83, krt86, and the Krtap genes include Krtap7-1, krtap8-1, krtap11-1, and the type II keratin gene is Kb23.
The tea composition further comprises a pharmaceutically acceptable excipient or carrier.
The applicant used the above composition for the treatment of PC12 cells of the rat adrenal pheochromocytoma cell line, analyzing its effect on the growth of PC12 cells neural cells. The specific operation is as follows:
1) Cell culture and drug treatment
PC12 cells were grown at 1X 10 5 inoculating/mL to the medium containingIn a culture dish of DMEM medium containing 10% FBS, it was placed in a culture dish containing 5% CO 2 Is cultured in a constant temperature incubator at 37 ℃. After 24h, 50. Mu. MA. Beta. Are used respectively 25-35 、50μM Aβ 25-35 +50μM EGCG、50μM Aβ 25-35 +50. Mu.M TFDG was treated for 24h. Control cells were added with an equal amount of sterile water.
2) Experimental materials
EGCG (. Gtoreq.99%) and TFDG (. Gtoreq.99%) were ordered from Shanghai Homopara Biolabs (Shangghai, china). The rat adrenal pheochromocytoma cell line PC12 cells were ordered from a pool of synergetic cells (beijin, china). Dulbecco's Modified Eagle's Medium (DMEM), fetal Bovine Serum (FBS) and trypsin were purchased from Biological Industries (Cromwell, CT, USA). Adenosine Triphosphate (ATP) detection kit, anti-fluorescence quenchers (containing DAPI) were purchased from the Biyun Tian Biotechnology institute (Shanghai, china). The rat nerve growth associated protein-43 (GAP 43) ELISA kit was purchased from Jiangsu Fei Biotech Co.
3) Analysis of the Effect of tea composition on axons
GAP43 expression in neurons is closely related to axonal elongation, synapse formation and nerve sprouting during development. ELISA kit detected growth-related protein-43 (GAP 43), and the results are shown in FIG. 2, and compared with Control group, abeta 25-35 GAP43 content of the group cells was significantly decreased (p<0.01). With Abeta 25-35 Group comparison, Aβ 25-35 GAP43 content of TFDG group cells was significantly increased (p<0.01). The results indicate that TFDG is able to promote the formation and development of axons.
Axons are rich in mitochondria, and mitochondrial dysfunction can lead to degeneration of cell axons. The white light photograph of the cell morphology shown in FIG. 4 shows that, compared with the Control group, abeta 25-35 The cell axes of the groups mutate finely and break; after 50 mu M EGCG and TFDG are added for dry prognosis, the cell axis mutation is coarse, the quantity is increased, wherein the effect of the TFDG is better than that of EGCG, and the ATP level detection result shown in FIG. 3 also proves that the intervention of EGCG and TFDG is beneficial to the cell axon growth.
The DAPI staining results shown in FIG. 5 indicate that Abeta compared to the Control group 25-35 Blue fluorescence of group nucleiThe light intensity is enhanced; with Abeta 25-35 Group comparison, Aβ 25-35 EGCG and Abeta 25-35 Blue fluorescence staining intensity of the TFDG group cell nucleus is reduced, the blue fluorescence staining intensity is basically consistent with that of Control group cells, and the staining is uniform, wherein the TFDG effect is more obvious, which indicates Abeta 25-35 Incubation promotes heterochromatin aggregation of the nuclei, whereas EGCG and TFDG have the effect of inhibiting heterochromatin aggregation of the nuclei.
4) Transcriptome analysis of tea composition to inhibit neuronal cell degeneration and promote axon growth
Cell samples were collected from the experimental and control groups, each group being provided with 3 biological replicates. Subsequently, all samples were sent to BGI company (Shenzhen, china) for further RNA-seq detection and analysis by BGISEQ-500 sequencer. HISAT 2%http://www.ccb.jhu.edu/software/hisat) For mapping clean reads to rat genomes. Bioinformatics analysis relies primarily on R language and on-line software for analysis and visualization. And screening the differential expression genes by using a Limma software package of R, wherein the I fold changes I is more than or equal to 2and adjusted p value and less than or equal to 0.05. The path analysis of the DEGs is performed based on GO and KEGG databases. Heat removal map (https:// gitsub. Com/CJChen/TBtools), all analyses were performed using the on-line bioinformatics platform Dr. Tom (biosys. BGI. Com /) provided by BGI.
We collected cell samples from different treatment groups for transcriptome sequencing analysis. Screening for significant differential expressed genes (discover differentially expressed genes, DEGs) through strict screening and quality control (the differential multiple is more than or equal to 2 times, p)<0.05 The results are shown in fig. 6): aβ 25-35 vs Aβ 25-35 67 EGCG groups were screened, 45 up-regulated genes and 22 down-regulated genes; aβ 25-35 vs Aβ 25-35 2012 were screened by the TFDG group, 199 up-regulated genes were used, 1813 down-regulated genes were used, and the result shows that TFDG incubation can significantly regulate (down-regulate/up-regulate) gene expression.
For Abeta 25-35 vs Aβ 25-35 TFDG differential expressed genes protein-protein interaction (PPI) network analysis was performed to identify key acting biosignal pathways and to functionally annotate module related genes, the results shown in fig. 7 demonstrate that: phase (C)The interacting genes are enriched in modules of estrogen signaling pathway, cell cycle, ubiquitination mediated proteolysis, metabolic pathways, etc. And notes are primarily shown to be upregulated in the estrogen signaling pathway and metabolic pathway network, and are primarily shown to be downregulated in the cell cycle and ubiquitination mediated proteolytic pathway network.
With Q value<0.05 was used as a standard for significant enrichment, and the differential gene GO enrichment results shown in fig. 8 indicate that: aβ 25-35 vs Aβ 25-35 The TFDG differential expression gene is remarkably enriched in the biological processes of transcription regulation, mRNA processing, microtubule-based movement, mitotic cell cycle and the like; the result of the enrichment of the functions of the differential genes KEGG shown in FIG. 9 shows that most of the enrichment signal paths which are significantly changed are significantly enriched in the paths related to neuroprotection and axon growth, and the enrichment signal paths relate to estrogen signal paths, cell cycle, regulation of actin cytoskeleton, focal adhesion, GAP connection and the like. These pathway changes suggest that TFDG bioactivity is closely related to neuroprotection and axon growth promotion.
For Aβ in FIG. 6 25-35 vs Aβ 25-35 The result of further analysis of the estrogen signal pathway module in the TFDG PPI network map is shown in fig. 10, in which there are 22 differentially expressed genes DEGs, including 18 keratin gene family members such as Krt15, krt16, krt83, etc.; 3 keratin-related proteins, one type II keratin 23, and the expression of these genes was in an up-regulated trend, with up-regulated expression of 6 keratin genes, krt5, krt17, krt25, krt27, krt31, and Krt35, in total, exceeding 100%.
Selective Estrogen Receptor Modulators (SERMs) are a class of non-steroidal compounds that bind to the ER and, depending on the target tissue and the in-hormonal environment, behave as estrogen agonists and/or estrogen antagonists, and are divided into five major classes depending on chemical structure: (1) a triphenylethylene compound; (2) benzothiophenes; (3) naphthalene compounds; (4) benzopyrans; (5) other classes of compounds. As can be seen from the differential gene heat map related to the estrogen signal pathway shown in FIG. 10, the active ingredient TFDG of the tea composition of the application, which is a benzopyran compound in the prior selective estrogen receptor modulator, acts as an estrogen agonist in the PC12 cell culture process, promotes the combination of estrogen and estrogen receptors ER alpha and ER beta, and activates target gene transcription to be one of classical estrogen signal pathways; the estrogen signaling pathway plays an important role in protecting nerve cells and promoting neurite growth, which is probably one of the important potential mechanisms of protecting nerve cells and promoting neurite growth of tea compositions using theaflavin as an active ingredient, and the applicant develops novel uses of tea compositions using TFDG as a main active ingredient based on the action mechanism.
The theaflavin monomers or compositions such as TFDG contain benzopyran chemical groups, the content of the chemical groups is higher, the chemical groups are the same as benzopyran compounds in the selective estrogen receptor modulators in the prior art, in addition, the TFDG contains more antioxidant structure conjugation effect and phenolic quinone balance than that of general catechin, has resting state repair effect on aged and hand damaged nerve cells, and remarkably promotes the expression of keratin favorable for axon growth by activating signal paths such as estrogen.
Use of a tea composition capable of modulating estrogen signaling pathway for the prevention and treatment of neurodegenerative diseases.
The specific method of use comprises administering to the patient an effective amount of a tea composition effective to up-regulate the expression of at least one of the Krt gene, the Krtap gene, the Kb gene by more than 40%.
Wherein, the tea composition can prevent or treat neurodegenerative diseases by up-regulating at least one Krt gene or Krtap gene expression by more than 40% and promoting the growth of nerve cell axon.
Preferably, the tea composition achieves prevention or treatment of neurodegenerative diseases by up-regulating expression of two or more Krt genes or Krtap genes by at least 40% or more, promoting neurite outgrowth in nerve cells.
Further preferably, the tea composition achieves prevention or treatment of neurodegenerative diseases by up-regulating expression of two or more Krt genes or Krtap genes or Kb23 genes by at least 40% or more, promoting neurite outgrowth in nerve cells.
The tea composition can prevent or treat neurodegenerative diseases by up-regulating 2 or more of Krt5, krt14, krt17, krt25, krt27, krt31 and Krt35 genes to express at least 40%.
The tea composition upregulates the estrogen signaling pathway in PC12 cells by binding to at least one estrogen receptor.
Example 2
An active ingredient of the tea composition of this example comprises theaflavin digallate and its derivative theaflavin-3-gallate (TF-3G), wherein the concentration of TFDG is 25 μm and the concentration of TF-3G is 25 μm, and wherein an effective amount of the tea composition is capable of up-regulating the estrogen signaling pathway in PC12 cells.
The effective amount is an amount effective to up-regulate the expression of at least one gene of a cytokeratin gene (keratins, abbreviated as Krt), a keratin-related protein gene (keratin-associated protein, abbreviated as Krtap), and a type II keratin gene (type II keratin, abbreviated as Kb) by 40% or more.
The Krt genes include Krt1, krt5, krt14, krt15, krt16, krt17, krt25, krt27, krt28, krt31, krt32, krt34, krt35, krt73, krt75, krt81, krt83, krt86, and the Krtap genes include Krtap7-1, krtap8-1, krtap11-1, and the type II keratin gene is Kb23.
The tea composition further comprises a pharmaceutically acceptable excipient or carrier.
The tea composition capable of regulating estrogen signal pathway is applied to preventing and treating neurodegenerative diseases.
The specific method of use comprises administering to the patient an effective amount of a tea composition effective to up-regulate the expression of at least one of the Krt gene, the Krtap gene, the Kb gene by more than 40%. The tea composition can prevent or treat neurodegenerative diseases by up-regulating 2 or more of Krt5, krt14, krt17, krt25, krt27, krt31 and Krt35 genes to express at least 40%.
The tea composition upregulates the estrogen signaling pathway in PC12 cells by binding to at least one estrogen receptor.
In addition, the application provides a tea composition capable of regulating estrogen signal pathway, wherein the theaflavin digallate derivative comprises theaflavin TF1, theaflavin-3-gallate (TF-3G), theaflavin-3 '-gallate (TF-3' G), thearubigin, theabrownin or other water extract of black tea.
According to the tea composition capable of regulating estrogen signal paths, a person skilled in the art can replace an active ingredient TFDG part in the embodiment 1 with other TFDG derivatives according to the difficulty of raw material acquisition, for example, the ratio of the TFDG to TF-3' G is 2:1 or TFDG and theaflavin TF1 are combined according to the mass ratio of 3:1, and the technical characteristics can be understood and implemented by a person skilled in the art through the text description, so that the description of the drawings is omitted.
In the description of the present application, it is to be understood that the terms "first", "second" and "third" may include one or more of such features, either explicitly or implicitly. In the description of the present application, unless otherwise indicated, the meaning of "a plurality" is two or more.
Claims (10)
1. Tea composition capable of modulating the estrogen signalling pathway, characterized in that the main active ingredient of the tea composition is theaflavin digallate (TFDG), and that an effective amount of the tea composition is capable of up-regulating the estrogen signalling pathway in PC12 cells.
2. The tea composition capable of modulating an estrogen signaling pathway according to claim 1, wherein the effective amount is an amount effective to up-regulate the expression of at least one of cytokeratin gene Krt, keratin related protein gene Krtap, type II keratin gene by about 40% or more.
3. A tea composition capable of modulating an estrogen signaling pathway according to claim 3 in which at least one Krt gene is selected from the group consisting of Krt1, krt5, krt14, krt15, krt16, krt17, krt25, krt27, krt28, krt31, krt32, krt34, krt35, krt73, krt75, krt81, krt83, and Krt86 and at least one Krtap gene is selected from the group consisting of Krtap7-1, krtap8-1, and Krtap11-1, type ii keratin gene is Kb23.
4. A tea composition capable of modulating an estrogen signaling pathway as defined in any one of claims 1 to 3 where the active ingredients of the tea composition comprise theaflavin digallate and derivatives thereof, and pharmaceutically acceptable salts, hydrates or any combination thereof.
5. A tea composition capable of modulating an estrogen signaling pathway according to claim 4, where the theaflavin digallate derivative comprises theaflavin TF1, theaflavin-3-gallate (TF-3G), theaflavin-3 '-gallate (TF-3' G), thearubigin, theabrownin.
6. Use of a tea composition according to any one of claims 1 to 5 which modulates the oestrogen signalling pathway in the prevention and treatment of neurodegenerative diseases.
7. Use of a tea composition having an adjustable estrogen signaling pathway for the prevention and treatment of neurodegenerative diseases as set forth in claim 6 wherein the method comprises administering to the patient an effective amount of the tea composition effective to up-regulate the expression of at least one Krt gene or Krtap gene by at least 40%.
8. Use of a tea composition capable of modulating an estrogen signaling pathway according to claim 7 for the prevention and treatment of neurodegenerative diseases by upregulating expression of two or more Krt genes by at least 40% or more to promote neurite outgrowth in nerve cells.
9. Use of a tea composition capable of modulating an estrogen signaling pathway as defined in claim 7 for the prevention and treatment of neurodegenerative diseases by upregulating expression of 2 or more of the genes Krt5, krt14, krt17, krt25, krt27, krt31, krt35 by at least 40% in a manner promoting neurite outgrowth in the neural cells.
10. Use of a tea composition capable of modulating an estrogen signaling pathway as defined in claim 7 for the prevention and treatment of neurodegenerative diseases wherein the tea composition upregulates estrogen signaling pathway in PC12 cells by binding to at least one estrogen receptor.
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| PCT/CN2022/103451 WO2023159850A1 (en) | 2022-02-26 | 2022-07-01 | Tea composition capable of regulating estrogen signaling pathway and use of same in prevention and treatment of neurodegenerative diseases |
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| CN102159203A (en) * | 2008-07-23 | 2011-08-17 | 麻省理工学院 | Activatiqn of histone deacetylase 1 (hdac1) protects against DNA damage and increases neuronal survival |
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