CN111000233A - Application of ECG as muscle building functional component - Google Patents
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- CN111000233A CN111000233A CN201911186616.1A CN201911186616A CN111000233A CN 111000233 A CN111000233 A CN 111000233A CN 201911186616 A CN201911186616 A CN 201911186616A CN 111000233 A CN111000233 A CN 111000233A
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Abstract
The invention relates to application of ECG as a muscle building functional component in food, and provides a dietary nutritional supplement containing green tea ECG and having muscle building effect. The supplement contains epicatechin gallate (ECG) extracted from green tea of natural plant source as main functional component. The invention can promote muscle regeneration, inhibit muscle protein degradation, inhibit oxidative damage of muscle protein, promote survival of muscle cells, improve exercise capacity and have extremely wide application value.
Description
Technical Field
The invention belongs to the technical field of food, and particularly relates to application of ECG as a muscle building functional component in food, and provides a dietary nutritional supplement containing green tea ECG and having a muscle building effect.
Background
The loss of skeletal muscle mass and strength is mostly caused by aging, muscle atrophy caused by chronic diseases, cachexia, sarcopenia and other diseases, these diseases can lead to a significant decrease in muscle fiber cross-sectional area, number of muscle nuclei, protein content and muscle strength, muscle fatigue and the appearance of insulin resistance phenomena, which in turn leads to an increase in patient mortality (Engler A J, Carag-Krieger C, Johnson C P, et al. organic cardiac muscle muscles bed stone on a matrix with heart-like elasticity bed coating [ J ]. J. CellSci, 2008, 121(Pt 22): 3794:. 802.;. Varga B, Martin-FernandeZ M, Hilaiire C, molecular elasticity of amorphous fibers model [ J ]. Sci 2018, 8(1): 5917). With age, after 50 years, muscle mass decreases at a rate of approximately 1% -2% per year (Li P, Liu A, Xiong W, et al, Catechins enhance skin muscle performance [ J ]. Crit Rev Food Sci Nutr, 2019: 1-14.; Vinctiuerra M, Fulco M, Ladurner A, et al, SirT1 in muscle physiology and disease: muscles from moods minerals [ J ]. Dis Model Mech, 2010, 3(5-6): 298 303.), whereas muscle strength decreases at a rate of 1.5% per year between 50-60 years, and thereafter at a rate of 3% per year. Adults have a low muscle turnover rate, are only able to sustain the body's growth and training needs, and regenerate in response to injury or disease. This regenerative capacity relies primarily on the proliferation, migration, differentiation and fusion of satellite cells adhering between the myomembrane and the basement membrane to form new multinucleated myotubes. The number of adult satellite cells is about 2% to 7% of the total number of muscle Cell nuclei (Kuno A, Horio Y. SIRT1: A Novel Target for the treatment of muscle dyestuffs [ J ]. Oxid Med Cell Longev, 2016, 2016:6714686.), whereas most of these satellite cells are in a resting State, and only 2% to 5% are in an activated State to maintain the muscle' S daily rotation of new and old (Fulco M, Schiltz R L, Iezzi S, et al, Sir2 regulations Skeleton muscle Differentiation as a Potential Sensor of the Redox State [ J ]. molecular Cell, 2003, 12(1): 51-62.). The differentiation of muscle-derived stem cells in muscle-related patients with cachexia, sarcopenia and the like is inhibited, while the muscle nutrients are continuously consumed, and the body is gradually thinned after a long time. Although there are a number of studies attempting to reduce Muscle loss by drug intervention, these drugs have limited effects and also have some toxic side effects (Dugdale H F, Hughes D C, Allan R, et al, The role of recovery on skin tissue differentiation and Muscle hyper-Control along glucose metabolism [ J ]. Mol Cell Biochem, 2018, 444(1-2): 109 and 123.; Zismanov V, Chichov, Colangio V, et al, Phosphorylation of eIF2 Is a transition of alpha Control Mechanism Regulating Muscle tissue reaction [ J ]. Cell 2016, 18 (1-79): 79). The search for safe and effective dietary nutritional supplements from natural products has made it possible to enhance muscle performance.
At present, the prior art CN1785223A discloses a medicine composition capable of treating myasthenia gravis and muscular atrophy, which comprises ginseng and epimedium and can obviously enhance muscle strength. Prior art CN105431057A discloses a catechin EGC capable of increasing muscle vascular endothelial growth factor a (vegf) levels, decreasing myostatin levels, and reducing a decrease in muscle function or improving muscle function. Prior art CN101978958A discloses a nutritional composition consisting of EGCG and resveratrol for the prevention and treatment of disorders causing muscle loss, atrophy and muscle wasting and other related muscle disorders in mammals. ECG is a catechin monomer in tea, and has been reported to have various physiological activities such as anti-inflammatory, anti-oxidation, anti-tumor, and cardiovascular and cerebrovascular system protection.
Disclosure of Invention
Although there are many reports on nutrients for enhancing muscle performance and ECG has been reported to have various physiological activities such as anti-inflammatory, anti-oxidation, anti-tumor, and protection of cardiovascular and cerebrovascular systems, there has been no report on Epicatechin gallate (ECG) for treating muscle atrophy and enhancing muscle performance. The present inventors have conducted long-term studies in this regard, and thus completed the present invention. Therefore, the invention aims to provide a pure natural plant source dietary nutrition supplement which can promote muscle regeneration, inhibit muscle protein degradation, inhibit oxidative damage of muscle protein, promote survival of muscle cells and improve exercise capacity.
The present inventors studied the induced differentiation activity test of catechin, and compared EC, ECG, EGC and EGCG with the strength of promoting the differentiation activity of C2C12 cells by detecting the relative expression amount of mRNA of myotube differentiation markers MyOD, MyOG and MyHC and measuring the number, length and diameter of myotubes after differentiation, the results showed that the differentiation promoting effect of ECG is stronger than that of other catechin monomers, and the differentiation promoting activity thereof has an increasing trend with increasing concentration.
The ECG used in the invention is high-purity ECG powder which is a pure natural green tea extract, and epicatechin gallate (ECG purity > 98%) monomer is obtained by separating and purifying green tea raw materials through the combination of ethyl acetate extraction, two different adsorption resin column chromatography adsorption separation, reverse osmosis membrane concentration and freeze drying technology, and the specific preparation method can be implemented by referring to patent CN 102432577A.
The above applications typically involve the preparation of the ECG as a dietary nutritional supplement. Preferably, the ECG mass fraction in the dietary nutritional supplement is 98% to 100%.
In specific application, the dosage form of the dietary nutrition supplement is selected from one of tablets, capsules, granules and pills. Furthermore, auxiliary materials are added into the dosage form of the dietary nutritional supplement. Preferably, the adjuvant is selected from dextrin, cellulose or cellulose derivatives, pectin, or gelatin.
In one embodiment, the dietary nutritional supplement is prepared by the following method: accurately weighing ECG powder, oven drying, sieving with 100-200 mesh sieve, preferably 100 mesh sieve, and tabletting to obtain dietary nutritional supplement.
In one embodiment, the dietary nutritional supplement is prepared by the following method: accurately weighing ECG powder, drying, sieving with 100-200 mesh sieve, preferably 200 mesh sieve, and making into capsule to obtain the dietary nutritional supplement.
In one embodiment, the dietary nutritional supplement is prepared by the following method: accurately weighing ECG powder, drying, sieving with 100-200 mesh sieve, preferably 200 mesh sieve, and granulating the sieved ECG powder by dry granulation to obtain the dietary nutritional supplement.
In administration, ECG is preferably administered in a dose of 0.1mg/kg to 0.4 mg/kg.
Through research, the ECG-containing dietary nutritional supplement provided by the invention has the beneficial effects that: it can enhance muscle strength, delay the onset of muscle atrophy due to aging and disease, and is a promising dietary nutritional supplement for maintaining muscle homeostasis and combating disuse muscle atrophy. By supplementing this dietary nutrition, prevention, alleviation, delay or even treatment of muscle-related disorders caused by aging and diseases in humans and animals can be achieved.
Drawings
FIG. 1A is a graph of myotube morphology after 4 days of differentiation of C2C12 cells cultured continuously with ECG at different concentrations;
FIG. 1B is a graph of myotube differentiation markers assayed at day 4 of cell differentiation
Wherein the relative expression amounts of MyoD, MyoG and MyHC mRNA are shown in this order.
Figure 1C shows the number, length and diameter of myotubes at day 4 of cell differentiation (5 pictures taken microscopically for each treatment, statistical mean).
FIG. 2A is a graph of myotube morphology of cells differentiated to various stages.
FIG. 2B shows mRNA expression levels of MyoD, MyoG and MyHC in myotubes at 0. mu.M, 10. mu.M and 20. mu.M of ECG-affected cells differentiated to 1, 2, 3, 4 and 5 days.
Fig. 2C is a statistic of myotube number, length and diameter matching fig. 2B.
FIG. 3A is a three-dimensional morphology of mature myotube cells and a Young's modulus of each region of myotube when the cells were differentiated to day 5 in the control group (0 μ M), respectively.
FIG. 3B is a three-dimensional topography of mature myotube cells and Young's modulus of each region of myotube when the cells were differentiated to day 5 in the experimental group (10 μ M ECG), respectively.
FIG. 3C is a statistical result of the height, stiffness, adhesion and Young's modulus of ECG on C2C12 differentiation to day five.
FIG. 4A is a gene expression pattern diagram of 179 cells with normal differentiation of C2C12 cells, wherein there are a tendency that the expression of 84 genes is up-regulated (Cluster 1) and the expression of 87 genes is down-regulated (Cluster 4). The heat maps on the left and right correspond to the expression patterns of up-regulated and down-regulated genes, respectively.
FIG. 4B shows IPA analysis of 171 genes with up-and down-regulated expression, which were found to be enriched in signaling pathways such as EIF2, Sirtuin, Rho, PPAR α/RXR α, and Ephrin.
FIG. 5A shows the results of SOM analysis continued with the addition of ECG treatment groups based on normal cell differentiation.
Figure 5B shows IPA analysis results on the selected 56 genes co-upregulated and 66 genes co-downregulated.
FIG. 6 shows the interaction network of genes involved in regulating muscle development (myogenesis, formation and function) detected by IPA in genes.
Detailed Description
The present invention will be described in detail with reference to the following examples, but the scope of the present invention is not limited thereto. The following examples mainly study the effect of ECG on promoting the differentiation of C2C12 cells and the mechanism thereof
Example 1: ECG enhanced differentiation of C2C12 cells
In order to evaluate the influence of ECG on the enhancement of the differentiation activity of C2C12 cells, two concentrations of 10 μ M and 20 μ M (specifically, the concentration of the effective functional component ECG) were selected and used for 4 days after respectively acting on C2C12 cells, and the phenotype and differentiation markers (differentiation markers) of myotubes were counted, wherein the items specifically comprise the number, length and diameter of myotubes, myogenic regulators MyoD, MyoG and the relative expression amount of mRNA of myosin heavy chain (MyHC). FIG. 1A is a graph of myotube morphology after 4 days of differentiation of different concentrations of ECG continuous culture C2C12 cells, including a blank control. FIG. 1B is a graph showing the relative expression levels of mRNA of MyoD, MyoG and MyHC in sequence, in the detection of myotube differentiation markers when cells were differentiated to day 4. Overall, after the action of ECG, the expression level of differentiation markers of myotubes is very high, and repeated experiments show similar results, so ECG has stronger differentiation promoting effect.
On the other hand, the number, length and diameter of myotubes at the time of cell differentiation to day 4 were also counted (5 pictures taken with a microscope for each treatment, statistical mean) to phenotypically more visually demonstrate the strong and weak differentiating effect of ECG, as shown in fig. 1C. The ECG showed strong stimulation at concentrations of 10. mu.M and 20. mu.M, both in the number of myotubes and in the length and diameter (increase in myotubes by 107.9% and 115.9%, respectively, in the 10. mu.M and 20. mu.M ECG, increase in length by 44.3% and 50.2%, respectively, and increase in diameter by 33.1% and 41.2%, respectively).
To determine the appropriate concentration of compound and to find the time points of action that promote greater differentiation markers differences for subsequent mass spectrometry experiments, we further investigated the ECG. The 3 concentrations of ECG selected at 0. mu.M, 10. mu.M and 20. mu.M were applied to the cells differentiated to the fifth day of the terminal phase, FIG. 2A is a graph of the morphology of myotubes as differentiated to each phase, and FIG. 2B is a graph of the mRNA expression levels of myoD, MyoG and MyHC at 0. mu.M, 10. mu.M and 20. mu.M of ECG-applied cells differentiated to 1, 2, 3, 4, 5 days, matching the statistics of myotube number, length and diameter of FIG. 2C. The results showed that the differentiation marker difference of the cells was more significant at the late stage of cell differentiation, i.e., at day 5, than at other time points, and the differentiation state of the cells was better when the concentration of ECG action was selected to be 10. mu.M.
Example 2: ECG can change the surface appearance and mechanical property of myotube cells
To explore the effect of ECG on myotube cell morphology and mechanical properties of differentiation to maturation stage, we selected ECG's selected at concentrations of 0 and 10 μ M for atomic force microscopy at the end of differentiation (day 5). FIGS. 3A and 3B are a three-dimensional morphology of mature myotube cells and Young's modulus of each region of myotube, as the cells differentiated to day 5 in the control group (0. mu.M) and the experimental group (10. mu.M ECG), respectively. FIG. 3C is a statistical result of the height, stiffness, adhesion and Young's modulus of ECG on C2C12 differentiation to day five. After cells were differentiated for 5 days by 10 μ M ECG, the height of mature myotubes increased from the original 2.226. + -. 0.122 (. mu.m) to 6.400. + -. 0.338 (. mu.m), with an increase of about 178.5%. On the other hand, after ECG treatment, the adhesion, rigidity and Young's modulus of the mature myotube cells were reduced to 27.9%, 25.1% and 56.4% of those of the control group, respectively. It is sufficient to see that the change of the mechanical properties of the cells by the ECG is very significant.
Example 3: proteomics analysis of possible molecular mechanisms of ECG-regulated myoblast differentiation
To further explore the mechanism of ECG-induced C2C12 cell differentiation, we performed whole proteomics analysis using liquid chromatography tandem mass spectrometry for three time points of early (0 day), middle (2 days) and late (5 days) of ECG on C2C12 cells, wherein the three time points were set to include undifferentiated group, differentiated 2 sky white control, differentiated 2 day ECG-treated group (10 μ M), differentiated 5 sky white control group and differentiated 5 day ECG-treated group (10 μ M), the 5 groups of cells were subjected to mass spectrometric detection and library comparison by extracting proteins respectively, and found to have 179 genes in common, using Genesis 1.8.1 software to perform SOM analysis of the expression levels of these genes, fig. 4A is a gene expression pattern diagram of 179 cells of C2C12 cells during normal differentiation, wherein 84 genes are expressed up-regulated (Cluster 1), expression levels of 4 genes are regulated down (Cluster 4), and the expression levels of these genes are found to be down-regulated up-regulated, down-regulated by PPAR 54, IPA, and the like, and we subsequently performed heat map of the expression patterns of these genes expressed up-regulated and down-regulated sirr α.
Then, on the basis of the normal differentiation of the cells, the group of ECG treatments was added, and the SOM analysis was continued, as shown in FIG. 5A, and it was found that 73 genes exhibited an up-regulation tendency (Cluster 5) and 88 genes exhibited a down-regulation tendency (Cluster 8) on the basis of the normal differentiation of the myotubes after the ECG treatment was added. Subsequently, the genes from the two SOM analyses were combined, 56 genes that were co-up-regulated were selected, and 66 genes that were co-down-regulated were further IPA analyzed, with the five signal pathways enriched being varied in intensity, as shown in fig. 5B. The most varied is found by comparison to be the Sirtuin signaling pathway. The data obtained from mass spectrometry of normal differentiation and differentiation enhanced by adding ECG were analyzed by using IPA software for upstream regulatory analyses, and the first ten Top upstream regulatory factors were predicted based on the difference between z-score and p-value: PPARGC1A, MYCN, TP53, INSR, XBP1, VEGFA, EPO, IL2, sirolimus, MYC (Table 1). At the same time, IPA also detected an interactive network of related genes among these genes that regulate muscle development (myogenesis, formation and function), as shown in fig. 6. Finally, there are 13 genes whose expression is down-regulated in normally differentiated cells and up-regulated with ECG, as compared to normal differentiated cells: cd44, Flnc, Hist1h1c, Pdia6, Pgk1, Psma5, Rps8, Serpinh1, Tpm4, Uba1, Vcl, Vcp, Ywhag.
TABLE 1 ECG action on the first 10 upstream regulatory factors in the myogenic differentiation data Gene set
| Upstream Regulator | Molecule Type | Activation z-score | P-value |
| PPARGC1A | transcription regulator | 2.411 | 8.26E-04 |
| MYCN | transcription regulator | -2.687 | 2.91E-11 |
| TP53 | transcription regulator | 2.991 | 4.74E-12 |
| INSR | kinase | 2.619 | 1.46E-06 |
| XBP1 | transcription regulator | 2.589 | 4.25E-05 |
| VEGFA | growth factor | 2.607 | 3.41E-04 |
| EPO | cytokine | 2.236 | 1.88E-03 |
| IL2 | cytokine | 2.449 | 3.90E-02 |
| sirolimus | chemical drug | 0.878 | 2.38E-19 |
| MYC | transcription regulator | -1.865 | 3.83E-18 |
The ECG can induce the differentiation of muscle-derived stem cells, maintain the dynamic balance between protein synthesis and degradation, increase the biosynthesis of mitochondria and capillaries, promote bone formation, protect the peripheral nervous system of skeletal muscles, resist inflammation and oxidation, enhance the glycolipid metabolic activity of organisms and the like.
Claims (8)
1. Application of ECG as functional component of muscle building in food is provided.
2. Use according to claim 1, characterized in that the ECG is a pure natural green tea extract.
3. Use according to claim 2, characterized in that: preparing the ECG into a dietary nutritional supplement.
4. Use according to claim 2, characterized in that: the ECG mass fraction in the dietary nutritional supplement is 98% to 100%.
5. Use according to any one of claims 1 to 4, wherein the ECG is administered in a dose of 0.1mg/kg to 0.4 mg/kg.
6. Use according to any one of claims 1 to 4, characterized in that: the dosage form of the dietary nutritional supplement is one selected from tablets, capsules, granules and pills.
7. Use according to any one of claims 1 to 4, characterized in that: the dosage form of the dietary nutritional supplement is also added with auxiliary materials.
8. Use according to claim 7, characterized in that: the adjuvant is selected from dextrin, cellulose or cellulose derivatives, pectin, or gelatin.
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| CN114752558A (en) * | 2021-05-27 | 2022-07-15 | 江南大学 | Application of flavonoids compounds in inducing myogenic cell in-vitro efficient differentiation |
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