Use of phytic acid in preparation of reagent for relieving mitochondrial impairment

Abstract

A use of a phytic acid in the preparation of a reagent for relieving mitochondrial impairment. The phytic acid has the effects of improving the average volume, surface area and length of mitochondria, reducing a sphericity rate, reducing the ROS level, reducing DNA damage, improving a G1 phase ratio, promoting removal of damaged mitochondria in cells, recycling metabolites in the cells and the like.

Description

Use of phytic acid in preparation of reagent for relieving mitochondrial damage TECHNICAL FIELD

[0001] The present application relates to the technical field of liquor, more particularly to use of phytic acid in preparation of reagent for relieving mitochondrial damage. BACKGROUND

[0002] Ethanol-induced mitochondrial damage is a key pathological process of alcoholic liver disease and other related diseases. In mitochondria, ethanol metabolism leads to the production of reactive oxygen species (ROS) and acetaldehyde. These metabolites are highly reactive, ROS damages cellular components by generating oxidative stress, while acetaldehyde can damage mitochondrial membranes and form adducts with mitochondrial DNA (mtDNA), leading to mitochondrial dysfunction and cell death. In the face of these damages, cells initiate a series of protective mechanisms to maintain homeostasis. For mtDNA damage, cells activate DNA repair pathways to repair mtDNA to maintain the integrity of the genome and correct transmission of genetic information. When the mitochondrial membrane is damaged, cells can eliminate damaged mitochondria by initiating autophagy. Autophagy is a selective form of autophagy involving the recognition, isolation and degradation of damaged mitochondria, and is an important way for cells to eliminate dysfunctional mitochondria and recycle their components.

[0003] Phytic acid (inositol hexaphosphate), as a natural substance present in various plant seeds, especially in plant seeds such as cereals, legumes, nuts and seeds, has attracted widespread attention in the scientific community for its potential role in cell protection, disease prevention and treatment, such as anti-inflammatory, anti-tumor and regulation of cell signaling, etc.

[0004] Therefore, whether phytic acid can be used to prepare a reagent for relieving mitochondrial damage is a problem that needs to be solved by those skilled in the art.

[0005] SUMMARY

[0006] Therefore, the present application provides use of phytic acid in preparation of a reagent for relieving mitochondrial damage.

[0007] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0008] Use of phytic acid in preparation of a reagent for relieving mitochondrial damage.

[0009] Preferably, the mitochondrial damage is induced by ethanol; and the mitochondria are mitochondria of hepatocytes.

[0010] Preferably, the effective concentration of the reagent for treating hepatocytes is 0.38-1.5 mmol / L.

[0011] Preferably: the alleviation is to improve the average volume, surface area, length of mitochondria, reduce the sphericity, reduce the ROS level, reduce DNA damage, increase the G1 phase ratio, promote the clearance of damaged mitochondria in cells and the recovery of metabolites in cells.

[0012] The application also provides the application of phytic acid in wine making.

[0013] The beneficial effect is that adjusting the concentration of phytic acid in wine making can reduce the impact of ethanol on the body (liver cells).

[0014] Through the above technical solution, compared with the prior art, the application provides the application of phytic acid in preparing a mitochondrial damage alleviating agent, and achieves the technical effect that the application finds that phytic acid has the effects of improving the average volume, surface area, length of mitochondria, reducing the sphericity, reducing the ROS level, reducing DNA damage, increasing the G1 phase ratio, promoting the clearance of damaged mitochondria in cells and the recovery of metabolites in cells. BRIEF DESCRIPTION OF DRAWINGS

[0015] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced below. Obviously, the drawings in the following description are only embodiments of the application, and other drawings can be obtained by those skilled in the art without creative labor on the basis of the provided drawings.

[0016] Figure 1 is a diagram provided by the application showing the effect of ethanol on liver cell mitochondria damage.

[0017] Figure 2 is a diagram provided by the application showing the effect of phytic acid on the survival rate of L02 cells.

[0018] Figure 3 is a diagram provided by the application showing the effect of phytic acid on ethanol-induced mitochondrial damage.

[0019] Figure 4 is a diagram provided by the application showing the effect of phytic acid on ethanol-induced DNA damage cell ROS.

[0020] Figure 5 is a diagram provided by the application showing the effect of phytic acid on ethanol-induced DNA damage protein.

[0021] Figure 6 is a diagram provided by the application showing the effect of phytic acid on ethanol-induced DNA damage cell cycle.

[0022] Figure 7 is a diagram provided by the application showing the effect of phytic acid on cell autophagy flux. DETAILED DESCRIPTION

[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] This invention discloses the application of phytic acid in the preparation of reagents to alleviate mitochondrial damage.

[0025] Example 1

[0026] Mitochondria are vital energy-producing organs within cells, responsible for generating ATP, the essential energy unit for life, through oxidative phosphorylation. Their health is crucial for cellular function. However, when mitochondria are damaged, their structure and function can be affected, threatening cellular survival. In response to damaged mitochondria, the cell initiates a series of morphological and functional changes. These changes begin with the fragmentation of the mitochondria, which breaks into multiple independent fragments along its length. This may be a self-protective mechanism, aiming to isolate the damaged parts to reduce overall damage. Subsequently, these mitochondrial fragments undergo further morphological changes, shrinking into a compact, spherical structure. This change helps to more effectively limit the spread of damage and prepares the cell for subsequent degradation or recycling of the damaged mitochondria. Ultimately, these damaged mitochondria are degraded and cleared by the cell through autophagy, a mechanism for maintaining cellular homeostasis and clearing internal damage. Through this process, the cell not only prevents further cellular damage caused by damaged mitochondria but also recycles mitochondrial components to support its own metabolic needs.

[0027] Construction of a model of ethanol-induced mitochondrial damage in hepatocytes

[0028] LO2 hepatocytes were treated with different concentrations of ethanol (0, 200, 400, and 600 mmol / L) for 6 hours. Then, pre-diluted mitochondrial orange fluorescent probe PK Mito Orange (1:1000, Nanjing Puhai Jingshan Biotechnology Co., Ltd., China) was added and stained under light-protected conditions. Super-resolution microscopy revealed significant changes in mitochondrial morphology, as shown in Figure 1 (Figure 1A: Effect of ethanol concentration on mitochondrial morphology in hepatocytes; Figure 1B: Changes in average mitochondrial volume, surface area, length, and globularity at different ethanol concentrations). With increasing ethanol concentration, the average volume, surface area, and length of mitochondria decreased significantly, while the globularity of mitochondria increased significantly. Based on these observations, an ethanol concentration of 600 mmol / L was selected as the condition for subsequent modeling experiments.

[0029] It is shown that ethanol exposure significantly affects the morphology of mitochondria in LO2 hepatocytes. With the increase of ethanol concentration, the decrease of mitochondrial volume, surface area and length reflects the response of cells to ethanol-induced stress. The decrease of mitochondrial volume and the change of morphology can be part of the cell's self-protection strategy, aiming to limit the spread of damage by reducing the number and volume of damaged mitochondria. The increase of mitochondrial spherical ratio indicates that under the action of ethanol, the morphology of mitochondria changes from slender or irregular to more rounded spherical. This change in morphology can be a sign that the cell initiates the autophagy process, especially selective autophagy of damaged mitochondria. This mechanism is an important way for the cell to remove damaged mitochondria and prevent them from causing further damage. The spheroidization of mitochondrial morphology can mark a critical stage before mitochondria are recognized and degraded.

[0030] Example 2

[0031] Effect of phytic acid on the survival rate of hepatocytes

[0032] LO2 hepatocytes were treated with phytic acid (0.38-6 mmol / L) for 24 h, and RPMI-1640 medium was used to dilute CCK-8 (Cell Counting Kit-8, Dojindo, Japan). After incubation for 2 h in the dark, the absorbance value at 450 nm was measured using a microplate reader, and the survival rate of cells was calculated. The results are shown in Figure 2. Compared with the untreated blank group, after phytic acid treatment, when the concentration was between 0.38 and 1.5 mmol / L, the cell survival rate did not show significant changes, indicating that phytic acid had no adverse effects on cell survival within this concentration range. However, at a concentration of 3 mmol / L, the cell survival rate decreased significantly to about 80% (P < 0.01), indicating that higher concentrations of phytic acid began to have a negative impact on cell survival. At a concentration of 6 mmol / L, the cell survival rate further decreased to about 38%, indicating that high concentrations of phytic acid had a significant inhibitory effect on cell survival. Based on these observations, the concentration of phytic acid selected in subsequent experiments should be controlled within 3 mmol / L to avoid negative effects on the survival of LO2 cells.

[0033] Example 3

[0034] Effect of phytic acid on ethanol-induced mitochondrial damage morphology

[0035] After 24h of pre-treatment with different concentrations of phytic acid, the cells were treated with 600mmol / L alcohol for 6h, then added with 1:1000 diluted mitochondrial orange fluorescent probe PK Mito Orange, and detected by super-resolution microscope. The results are shown in Figure 3 (Figure 3A: Effect of phytic acid pre-treatment on ethanol-induced mitochondrial damage, negative control is blank experiment, positive control is treated with 600mmol / L alcohol only; Figure 3B: Changes of average volume, surface area, length and sphericity of mitochondria under different concentrations of phytic acid).

[0036] Compared with the negative control group, the average volume, surface area and length of mitochondria in the positive control group were significantly reduced, while the sphericity was significantly increased. This indicates that ethanol treatment leads to damage of mitochondrial structure. In the experimental groups pre-treated with different concentrations of phytic acid, the average volume of mitochondria at the concentration of 0.19mmol / L was not significantly different from that of the positive control group; however, in the concentration range of 0.38 to 1.5mmol / L, the average volume of mitochondria was significantly improved compared with the positive control group, and was not significantly different from the negative control group. For the average surface area, there was no significant difference at the concentration of 0.19mmol / L compared with the positive control group; at the concentrations of 0.38 and 0.75mmol / L, the average surface area was significantly increased compared with the negative control group, and at the concentration of 1.5mmol / L, it was significantly improved compared with the positive control group, and was not significantly different from the negative control group. In terms of average length, in the concentration range of 0.19 to 1.5mmol / L, it was significantly improved compared with the positive control group, and at the concentrations of 0.38 and 0.75mmol / L, it was significantly increased compared with the negative control group. The sphericity at the concentrations of 0.19 to 1.5mmol / L was significantly reduced compared with the positive control group, and at the concentrations of 0.38 to 1.5mmol / L, it was also significantly reduced compared with the negative control group.

[0037] The experimental results reveal that phytic acid pre-treatment has a significant protective effect on ethanol-induced mitochondrial damage in L02 hepatocytes in terms of morphology, especially at higher concentrations (0.38-1.5mmol / L), phytic acid can effectively improve the average volume, surface area, length of mitochondria, and reduce the sphericity.

[0038] Since the damage of mitochondria includes mtDNA damage and membrane damage, the mechanism of this protective effect may involve the removal of reactive oxygen species (ROS), the reduction of mitochondrial DNA (mtDNA) damage, and the regulation of mitophagy, which will be further detected in subsequent examples.

[0039] Example 4

[0040] The metabolism of ethanol generates a large amount of ROS, which are highly reactive molecules that attack mitochondrial structures, causing membrane lipid peroxidation, damage to proteins and DNA, and ultimately leading to mitochondrial dysfunction. Phytic acid can protect mitochondria from damage by directly scavenging ROS and reducing ethanol-induced oxidative stress. In addition, by reducing ROS levels, phytic acid can also indirectly reduce the changes in intracellular signaling triggered by oxidative stress, preventing cells from entering the programmed death pathway.

[0041] Effect of phytic acid on ROS production in ethanol-induced hepatocyte damage

[0042] After 24 h of pretreatment with different concentrations of phytic acid, the cells were treated with 600 mmol / L alcohol for 6 h. Intracellular ROS was detected by flow cytometry using a fluorescence probe (reactive oxygen species assay kit, Biyun Tian Biotechnology Co., Ltd., Shanghai, China). The results are shown in Figure 4 (Figure 4A: Effect of phytic acid pretreatment on ROS in ethanol-induced hepatocyte damage, Figure 4B: Fluorescence image of ROS in ethanol-induced hepatocyte damage after phytic acid pretreatment, Figure 4C: Relative fluorescence ratio of ROS in ethanol-induced hepatocyte damage after phytic acid pretreatment). Compared with the negative control group, the relative fluorescence intensity of ROS in the positive control group was significantly increased (P < 0.01), indicating that ethanol metabolism significantly increased the production of intracellular ROS. The relative fluorescence intensity of ROS in cells pretreated with different concentrations (0.09-1.5 mmol / L) of phytic acid was significantly decreased (P < 0.01), indicating that phytic acid can effectively reduce ethanol-induced ROS production. The experimental results confirmed the large production of ROS during ethanol metabolism, which are highly reactive molecules that attack mitochondrial structures, causing membrane lipid peroxidation and damage to proteins and DNA, ultimately leading to mitochondrial dysfunction. This phenomenon is consistent with the mechanism of ethanol-induced cell damage and pathological processes, highlighting the key role of ROS in the toxic effects of ethanol.

[0043] Phytic acid showed significant antioxidant activity in this experiment. Pretreatment with different concentrations of phytic acid significantly reduced the ROS level caused by ethanol treatment, which might be achieved by directly scavenging ROS molecules. This mechanism of action indicates that phytic acid can protect mitochondria from ethanol-induced oxidative damage, thereby alleviating the oxidative stress status in cells. In addition to direct ROS scavenging, the effect of phytic acid in reducing ROS production might also be achieved by affecting the signaling pathways within the cells, thereby reducing cell death triggered by oxidative stress. This protective mechanism might include the inhibition of ROS-sensitive signaling pathways such as MAPK, NF-κB, etc., which play a key role in cellular response to oxidative stress and regulation of cell survival and death. Furthermore, by reducing ROS levels, phytic acid might indirectly promote the protection of mitochondrial DNA and the balance of mitochondrial autophagy, thereby maintaining the structural integrity and function of mitochondria. This indicates that phytic acid can not only act as an antioxidant to alleviate direct oxidative damage, but also might alleviate ethanol-induced cellular damage by regulating protective mechanisms within the cells.

[0044] Example 5

[0045] Effect of phytic acid on ethanol-induced DNA damage proteins

[0046] Damage to mitochondrial DNA is another key factor of ethanol toxicity. Ethanol-induced ROS not only affects the structure of mitochondrial membranes, but also directly damages mtDNA, leading to loss of genetic information and mitochondrial dysfunction. If this damage is not repaired in time, it will trigger the emergency response of cells, including the suspension of the cell cycle, and p-H2AX is a key marker of the cellular response to DNA damage.

[0047] After 24 h of phytic acid pretreatment at different concentrations, the cells were treated with 600 mmol / L alcohol for 6 h, collected, and labeled with anti-p-H2AX antibody (Bi Yun Tian Biotechnology Co., Ltd., Shanghai, China). The results of Western blot detection are shown in Figure 5 (Figure 5A: Effect of phytic acid on p-H2AX protein after ethanol-induced liver cell damage, Figure 5B: p-H2AX / GAPDH ratio of phytic acid on ethanol-induced liver cell damage). Compared with the negative control group, the expression level of p-H2AX protein in the positive control group was significantly increased, indicating the aggravation of DNA damage. However, after the cells were pretreated with phytic acid at a concentration ranging from 0.09 to 3 mmol / L, the expression of p-H2AX protein was significantly reduced (P < 0.01), indicating that phytic acid effectively alleviated the DNA damage caused by ethanol. In particular, at a phytic acid concentration of 1.5 mmol / L, the content of p-H2AX protein was not only significantly lower than that of the positive control group, but even lower than that of the negative control group, showing the best DNA repair effect (P < 0.01). Notably, at a phytic acid concentration of 3 mmol / L, the expression level of p-H2AX was lower than that of the positive control group, but it rebounded compared to other phytic acid treatment concentrations, suggesting that the protective effect of phytic acid at this concentration may have started to weaken.

[0048] By reducing ROS production and DNA damage, phytic acid not only protects mitochondrial structure and function, but also may affect the normal progress of the cell cycle. Phytic acid at a certain concentration can significantly reduce the expression of p-H2AX in cells after ethanol treatment, suggesting its potential role in promoting DNA damage repair and maintaining the normal progress of the cell cycle. Therefore, the detection of the cell cycle will be an important next step in evaluating the protective effect of phytic acid on ethanol-induced mitochondrial damage.

[0049] Example 6

[0050] Effect of phytic acid on ethanol-induced cell cycle arrest

[0051] The operation of the cell cycle follows a set of strict control systems to ensure that each step is only started after the previous step is completed. In the G1 phase, the cell is growing and preparing for DNA replication. The cell performs DNA replication in the S phase and G2 phase, and prepares for the next division stage. When the cell faces unfavorable environmental conditions, such as lack of nutrients, this control system can adjust the speed of the cell cycle, or even temporarily stop the cell cycle to give the cell time and opportunity to cope with the challenge. In particular, when the cell's DNA is damaged, the importance of this control mechanism is more prominent, as it will pause the cell cycle, allowing the DNA damage repair system to intervene and repair the damaged DNA to ensure the normal operation and survival of the cell.

[0052] After 24 h of pre-treatment with different concentrations of phytic acid, cells were treated with 600 mmol / L ethanol for 6 h. The results are shown in Figure 6 (Figure 6A: Effect of different concentrations of phytic acid (0.09, 0.19, 0.38, 0.75, 1.5 mmol / L) on cell cycle after ethanol-induced liver cell damage, Figure 6B: G1 / (G1+S+G2) ratio of phytic acid on ethanol-induced liver cell damage). The results showed that the positive control group significantly reduced the ratio of cells in the G1 phase (P < 0.01), suggesting that ethanol treatment caused cell cycle progression to be blocked. However, when cells were pre-treated with phytic acid at concentrations ranging from 0.09 to 0.75 mmol / L, the G1 phase ratio was significantly increased (P < 0.01), indicating that phytic acid can effectively alleviate ethanol-induced cell cycle arrest. Notably, at a concentration of 1.5 mmol / L phytic acid, there was no significant difference in the G1 phase ratio compared to the positive control group, suggesting that the protective effect of phytic acid on ethanol-induced cell cycle at this concentration may have reached saturation or weakened.

[0053] The significant decrease in the G1 phase ratio of cells treated with ethanol may be related to the ROS and DNA damage produced during ethanol metabolism. These damages activate the cell cycle checkpoint response, causing cells to arrest in the G1 phase for DNA repair. However, prolonged G1 phase arrest can hinder normal cell growth and division, affecting cell health. Phytic acid shows a protective effect on ethanol-induced cell cycle arrest by increasing the G1 phase ratio. This protective effect may be due to the antioxidant properties of phytic acid, reducing ROS production, protecting DNA from damage, and thus reducing the activation of the cell cycle checkpoint.

[0054] Example 7

[0055] Effect of phytic acid on autophagic flux of liver cells

[0056] Mitophagy is a key mechanism for maintaining mitochondrial quality control and plays an important role in the timely removal of damaged mitochondria. The triggering of mitophagy involves various signals and pathways, including loss of mitochondrial membrane potential, mitochondrial DNA damage, and oxidative stress. Once mitochondria are marked for degradation, they are wrapped in autophagosomes and eventually fuse with lysosomes and are degraded. This process not only helps to remove damaged mitochondria, but also promotes the renewal of mitochondria and the recycling of intracellular metabolites, playing an important role in maintaining cellular metabolic balance and physiological function. Phytic acid pre-treatment may help cells more effectively remove damaged mitochondria by activating or enhancing the efficiency of mitophagy, maintaining the stability of the intracellular environment.

[0057] In the process of autophagy activation, the expression of P62 protein in LO2 cells decreased, the expression of LC3 protein increased, and the degradation of cell components indicated that the autophagy activity of LO2 cells was enhanced. LC3 is the homolog of ATG8 protein in mammals, and it is a key factor in the autophagy process. The LC3 protein family is composed of multiple subfamilies, including LC3A, B, C and GABARAP, and the research on LC3B is the most in-depth. According to existing research, LC3B is considered the most important marker protein in the autophagy signaling pathway. After transducing the pCMV-GFP-LC3B plasmid with green fluorescence in cells, in the non-autophagy state, the successfully transduced cells will emit green GFP-LC3B fluorescence, and this fluorescence will exist in the cytoplasm in a scattered manner. However, when the cell is in the autophagy state, GFP-LC3B will gather on the autophagosome membrane, showing in the form of spots.

[0058] Green fluorescent protein (GFP) and red fluorescent protein (RFP) are fused to LC3 as new autophagy activity assay probes: GFP-LC3-RFP-LC3AG (see patent: CN116987756A, patent name: A detection method for the influence of trace components in wine body on cell autophagy flux). This probe is more distinctive after formation in cells than the previous type, and can be trimmed by ATG4 protein, which will produce GFP-LC3 and RFP-LC3AG in a one-to-one ratio, that is, the production of each GFP-LC3 is accompanied by the generation of one RFP-LC3AG. In the cytoplasm, GFP-LC3 will emit green fluorescence. However, when the autophagosome merges with the lysosome, the green fluorescence of GFP-LC3 will disappear, and only the red fluorescence of RFP-LC3AG can be seen. This is because the green fluorescence of GFP will weaken in an acidic environment. On the other hand, due to the lack of the necessary terminal glycine, RFP-LC3AG cannot be lipidized and stays in the cell, so the number of RFP-LC3AG emitting red fluorescence remains basically unchanged and can be used as a stable standard for fluorescence reaction. Therefore, the ratio of the fluorescence intensity of GFP and RFP is an indicator of autophagy activity, and the lower the GFP / RFP ratio, the higher the autophagy activity.

[0059] The effect of phytic acid on autophagic activity was evaluated using a red, green dual fluorescent protein labeled LO2 cell model treated with different concentrations (0, 0.19, 0.38, 0.75, 1.5, 3 mmol / L) of phytic acid for 24 hours. The experimental results are shown in Figure 7 (Figure 7A: GFP, RFP fluorescence peak value graph of phytic acid at different concentrations; Figure 7B: GFP / RFP relative ratio of phytic acid at different concentrations). With the increase of the concentration of phytic acid, the intensity of green fluorescence (representing GFP-LC3) was observed to weaken, and the overall peak moved to the left, while the intensity of red fluorescence (representing RFP-LC3AG) remained unchanged. Therefore, the ratio of GFP / RFP was significantly reduced, indicating the enhancement of autophagic activity. In the process of autophagy, the weakening and leftward movement of the fluorescence intensity of GFP-LC3 reflect the aggregation of GFP-LC3 and its degradation with the fusion of autophagosomes with lysosomes, while RFP-LC3AG remains stable due to its structural properties and is not affected by the acidic environment during autophagosome-lysosome fusion. Therefore, the significant reduction of the GFP / RFP ratio directly indicates the increase of autophagic flux with the increase of the concentration of phytic acid, indicating that phytic acid promotes the clearance of damaged mitochondria and the recycling of intracellular metabolites, thereby maintaining the metabolic balance and physiological function of cells.

[0060] Experiments show the potential role of phytic acid in regulating the intracellular environment, especially in promoting the timely clearance of damaged mitochondria. Mitophagy, as an important cellular quality control mechanism, plays a crucial role in preventing cellular stress and maintaining cellular homeostasis. Phytic acid may provide a protective mechanism against cell damage caused by factors such as ethanol by enhancing mitochondrial autophagy.

[0061] The various embodiments in the specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0062] The above description of the disclosed embodiments enables a person skilled in the art to implement or use the present application. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. Use of phytic acid in the preparation of an agent for alleviating mitochondrial damage.

2. The use according to claim 1, characterized in that, The mitochondrial damage is induced by ethanol; the mitochondria are mitochondria of hepatocytes.

3. The use according to claim 2, wherein The effective concentration of the agent for treating hepatocytes is 0.38-1.5 mmol / L.

4. The use according to claim 3, characterized in that, The alleviation is improvement of the average volume, surface area, length of mitochondria, reduction of the sphericity, reduction of the ROS level, reduction of DNA damage, increase of the G1 phase ratio, promotion of the clearance of damaged mitochondria in cells and recovery of metabolites in cells.

5. Use of phytic acid in wine making.

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